Trial Outcomes & Findings for Efficacy and Safety of Aldoxorubicin Compared to Topotecan in Subjects With Metastatic Small Cell Lung Cancer (NCT NCT02200757)

NCT ID: NCT02200757

Last Updated: 2024-06-25

Results Overview

PFS is defined as the time from the date of randomization to first documentation of objective tumor progression or to death due to any cause in the absence of previous documentation of objective tumor progression. Progressive Disease is defined as: ≥20% increase in the sum of the longest diameter of target lesions from the smallest sum of the longest diameter recorded since the treatment started; the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of ≥1 new lesion is also considered progression.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 135 participants
• Primary outcome timeframe: 24 months
• Results posted on: 2024-06-25

Participant Flow

135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start.

Participant milestones

Measure	Aldoxorubicin Aldoxorubicin: 230 mg/m\^2 (170 mg/m\^2 doxorubicin equivalent) intravenously on Day 1 of each 21-day cycle. Number of cycles: until tumor progression or unacceptable toxicity occurs.	Topotecan Topotecan: 1.5 mg/m\^2/day intravenously for 5 consecutive days on Day 1 of each 21-day cycle OR 4 mg/m\^2 intravenously on Days 1, 8 and 15 of each 28-day cycle. Number of cycles: until tumor progression or unacceptable toxicity occurs
Overall Study STARTED	67	63
Overall Study COMPLETED	67	63
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Efficacy and Safety of Aldoxorubicin Compared to Topotecan in Subjects With Metastatic Small Cell Lung Cancer

Baseline characteristics by cohort

Measure	Aldoxorubicin n=69 Participants Aldoxorubicin: 230 mg/m2 (170 mg/m2 doxorubicin equivalent) intravenously on Day 1 of each 21-day cycle. Number of cycles: until tumor progression or unacceptable toxicity occurs.	Topotecan n=66 Participants Topotecan: 1.5 mg/m2/day intravenously for 5 consecutive days on Day 1 of each 21-day cycle OR 4 mg/m2 intravenously on Days 1, 8 and 15 of each 28-day cycle. Number of cycles: until tumor progression or unacceptable toxicity occurs	Total n=135 Participants Total of all reporting groups
Age, Continuous	65.3 years STANDARD_DEVIATION 6.73 • n=5 Participants	63.5 years STANDARD_DEVIATION 7.72 • n=7 Participants	64.42 years STANDARD_DEVIATION 0 • n=5 Participants
Sex: Female, Male Female	34 Participants n=5 Participants	26 Participants n=7 Participants	60 Participants n=5 Participants
Sex: Female, Male Male	35 Participants n=5 Participants	40 Participants n=7 Participants	75 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	7 Participants n=7 Participants	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	61 Participants n=5 Participants	56 Participants n=7 Participants	117 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) White	64 Participants n=5 Participants	62 Participants n=7 Participants	126 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Subjects with Metastatic Small Cell Lung Cancer	69 Participants n=5 Participants	66 Participants n=7 Participants	135 Participants n=5 Participants

PRIMARY outcome

Timeframe: 24 months

Population: PFS is measured from randomization, not from treatment start date. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm.

PFS is defined as the time from the date of randomization to first documentation of objective tumor progression or to death due to any cause in the absence of previous documentation of objective tumor progression.

Progressive Disease is defined as: ≥20% increase in the sum of the longest diameter of target lesions from the smallest sum of the longest diameter recorded since the treatment started; the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of ≥1 new lesion is also considered progression.

Outcome measures

Measure	Aldoxorubicin n=69 Participants Aldoxorubicin: 230 mg/m2 (170 mg/m2 doxorubicin equivalent) intravenously on Day 1 of each 21-day cycle. Number of cycles: until tumor progression or unacceptable toxicity occurs.	Topotecan n=66 Participants Topotecan: 1.5 mg/m2/day intravenously for 5 consecutive days on Day 1 of each 21-day cycle OR 4 mg/m2 intravenously on Days 1, 8 and 15 of each 28-day cycle. Number of cycles: until tumor progression or unacceptable toxicity occurs
Progression-Free Survival (PFS)	1.5 Months Interval 1.4 to 2.7	2.7 Months Interval 1.5 to 3.0

SECONDARY outcome

Timeframe: Treatment was planned to continue until tumor progression is observed, subject asks to withdraw, or unacceptable toxicity occurs, up to 451 days.

Outcome measures

Measure	Aldoxorubicin n=67 Participants Aldoxorubicin: 230 mg/m2 (170 mg/m2 doxorubicin equivalent) intravenously on Day 1 of each 21-day cycle. Number of cycles: until tumor progression or unacceptable toxicity occurs.	Topotecan n=63 Participants Topotecan: 1.5 mg/m2/day intravenously for 5 consecutive days on Day 1 of each 21-day cycle OR 4 mg/m2 intravenously on Days 1, 8 and 15 of each 28-day cycle. Number of cycles: until tumor progression or unacceptable toxicity occurs
Number of Participants With Treatment-related Toxicities (Adverse Events)	51 Participants	52 Participants

Adverse Events

Aldoxorubicin

Serious events: 17 serious events

Other events: 61 other events

Deaths: 57 deaths

Topotecan

Serious events: 18 serious events

Other events: 61 other events

Deaths: 50 deaths

Serious adverse events

Measure	Aldoxorubicin n=67 participants at risk Aldoxorubicin: 230 mg/m2 (170 mg/m2 doxorubicin equivalent) intravenously on Day 1 of each 21-day cycle. Number of cycles: until tumor progression or unacceptable toxicity occurs.	Topotecan n=63 participants at risk Topotecan: 1.5 mg/m2/day intravenously for 5 consecutive days on Day 1 of each 21-day cycle OR 4 mg/m2 intravenously on Days 1, 8 and 15 of each 28-day cycle. Number of cycles: until tumor progression or unacceptable toxicity occurs
Infections and infestations Pneumonia	4.5% 3/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	3.2% 2/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Infections and infestations Respiratory tract infection	1.5% 1/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	1.6% 1/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Infections and infestations Anal abscess	0.00% 0/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	1.6% 1/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Infections and infestations Bronchitis	1.5% 1/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	0.00% 0/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Infections and infestations Empyema	1.5% 1/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	0.00% 0/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Infections and infestations Influenza	0.00% 0/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	1.6% 1/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Infections and infestations Pneumonia haemophilus	1.5% 1/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	0.00% 0/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Infections and infestations Urinary tract infection	1.5% 1/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	0.00% 0/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Blood and lymphatic system disorders Neutropenia	1.5% 1/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	4.8% 3/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Blood and lymphatic system disorders Anaemia	3.0% 2/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	1.6% 1/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	3.2% 2/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Blood and lymphatic system disorders Pancytopenia	0.00% 0/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	3.2% 2/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	3.2% 2/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Blood and lymphatic system disorders Lymphopenia	0.00% 0/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	1.6% 1/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Gastrointestinal disorders Stomatitis	3.0% 2/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	0.00% 0/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Gastrointestinal disorders Abdominal pain lower	1.5% 1/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	0.00% 0/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Gastrointestinal disorders Gastrointestinal hypomobility	1.5% 1/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	0.00% 0/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Gastrointestinal disorders Nausea	1.5% 1/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	0.00% 0/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Gastrointestinal disorders Vomiting	1.5% 1/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	0.00% 0/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	1.6% 1/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	1.6% 1/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.5% 1/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	0.00% 0/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Respiratory, thoracic and mediastinal disorders Pneumonitis	1.5% 1/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	0.00% 0/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
General disorders Gait disturbance	0.00% 0/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	1.6% 1/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
General disorders Inflammation	0.00% 0/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	1.6% 1/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
General disorders Pain	0.00% 0/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	1.6% 1/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Metabolism and nutrition disorders Hypokalaemia	1.5% 1/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	1.6% 1/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Metabolism and nutrition disorders Gout	1.5% 1/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	0.00% 0/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Cardiac disorders Atrial fibrillation	0.00% 0/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	1.6% 1/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Cardiac disorders Myocardial infarction	1.5% 1/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	0.00% 0/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Investigations Neutrophil count decreased	0.00% 0/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	1.6% 1/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	1.6% 1/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Nervous system disorders Cerebral infarction	1.5% 1/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	0.00% 0/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Psychiatric disorders Delirium	1.5% 1/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	0.00% 0/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.

Other adverse events

Measure	Aldoxorubicin n=67 participants at risk Aldoxorubicin: 230 mg/m2 (170 mg/m2 doxorubicin equivalent) intravenously on Day 1 of each 21-day cycle. Number of cycles: until tumor progression or unacceptable toxicity occurs.	Topotecan n=63 participants at risk Topotecan: 1.5 mg/m2/day intravenously for 5 consecutive days on Day 1 of each 21-day cycle OR 4 mg/m2 intravenously on Days 1, 8 and 15 of each 28-day cycle. Number of cycles: until tumor progression or unacceptable toxicity occurs
Blood and lymphatic system disorders Anaemia	23.9% 16/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	39.7% 25/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Blood and lymphatic system disorders Neutropenia	17.9% 12/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	33.3% 21/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Blood and lymphatic system disorders Thrombocytopenia	4.5% 3/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	47.6% 30/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Blood and lymphatic system disorders Leukopenia	3.0% 2/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	6.3% 4/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Blood and lymphatic system disorders Lymphopenia	6.0% 4/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	3.2% 2/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
General disorders Fatigue	20.9% 14/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	20.6% 13/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
General disorders Asthenia	14.9% 10/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	23.8% 15/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
General disorders Chest pain	3.0% 2/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	6.3% 4/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
General disorders Gait disturbance	3.0% 2/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	6.3% 4/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
General disorders Oedema peripheral	7.5% 5/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	0.00% 0/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Gastrointestinal disorders Nausea	17.9% 12/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	17.5% 11/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Gastrointestinal disorders Constipation	13.4% 9/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	14.3% 9/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Gastrointestinal disorders Stomatitis	19.4% 13/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	7.9% 5/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Gastrointestinal disorders Diarrhoea	9.0% 6/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	14.3% 9/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Gastrointestinal disorders Vomiting	10.4% 7/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	9.5% 6/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Gastrointestinal disorders Abdominal pain	0.00% 0/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	6.3% 4/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Metabolism and nutrition disorders Decreased appetite	17.9% 12/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	15.9% 10/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Metabolism and nutrition disorders Hypokalaemia	7.5% 5/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	4.8% 3/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Metabolism and nutrition disorders Hypomagnesaemia	7.5% 5/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	4.8% 3/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Metabolism and nutrition disorders Dehydration	4.5% 3/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	6.3% 4/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Metabolism and nutrition disorders Hyponatraemia	6.0% 4/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	4.8% 3/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	19.4% 13/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	9.5% 6/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Respiratory, thoracic and mediastinal disorders Cough	10.4% 7/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	12.7% 8/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Respiratory, thoracic and mediastinal disorders Productive cough	6.0% 4/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	1.6% 1/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Infections and infestations Upper respiratory tract infection	4.5% 3/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	6.3% 4/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Infections and infestations Urinary tract infection	6.0% 4/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	4.8% 3/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Infections and infestations Pneumonia	6.0% 4/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	3.2% 2/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Infections and infestations Respiratory tract infection	6.0% 4/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	3.2% 2/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Infections and infestations Bronchitis	6.0% 4/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	1.6% 1/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Nervous system disorders Headache	10.4% 7/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	3.2% 2/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Nervous system disorders Dizziness	3.0% 2/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	9.5% 6/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Nervous system disorders Dysgeusia	3.0% 2/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	6.3% 4/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Investigations Platelet count decreased	6.0% 4/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	15.9% 10/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Investigations Neutrophil count decreased	10.4% 7/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	6.3% 4/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Investigations White blood cell count decreased	1.5% 1/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	6.3% 4/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Musculoskeletal and connective tissue disorders Back pain	9.0% 6/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	9.5% 6/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Musculoskeletal and connective tissue disorders Arthralgia	4.5% 3/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	7.9% 5/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	3.0% 2/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	9.5% 6/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.
Musculoskeletal and connective tissue disorders Pain in extremity	7.5% 5/67 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.	1.6% 1/63 • All AEs and SAEs that occurred after any administration of the study medication were to be followed until the event resolved, until the subject began alternative treatment, or until 30 days after the last dose of study medication, up to 451 days. 2 subjects were randomized, but not treated in the Aldoxorubicin Arm. 3 subjects were randomized, but not treated in the Topotecan Arm. 135 subjects were enrolled in the intent to treat population, whereas 130 subjects were in the safety population. 5 subjects were discontinued prior to treatment start. Mortality was assessed in all enrolled subjects. AEs/SAEs were assessed in the safety population, all patients who received at least one dose of any study drug.

Additional Information

Sandeep Bobby Reddy, Chief Medical Officer

ImmunityBio

Phone: 855-797-9277

Email: Bobby.Reddy@Immunitybio.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place