Trial Outcomes & Findings for Topotecan and Bevacizumab in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer That Did Not Respond to Previous Systemic Chemotherapy (NCT NCT00365547)

Last Updated: 2017-12-28

Results Overview

Assessed by Response Evaluation Criteria In Solid Tumor (RECIST criteria). Progression is defined as a measureable increase in the smallest dimension of any target or non-target lesion, or the appearance of new lesions since baseline.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

46 participants

Primary outcome timeframe

From Day 1 Until First Documented Disease Progression or Date of Death (Whichever Occurred First)

Results posted on

2017-12-28

Participant Flow

46 patients were enrolled, only 43 patients received study medication

Participant milestones

Participant milestones
Measure	Intent-To-Treat Population Patients who enrolled and were scheduled to receive weekly topotecan (4 mg/m\^2 will be given as a 30-minute intravenous infusion on days 1, 8, and 15 with a rest on day 22 and repeated every 28 days) and bi-weekly Avastin (bevacizumab given by IV infusion at the dose of 10 mg/kg on days 1 and 15 after topotecan administration)in patients with non-small cell lung cancer (NSCLC) who have failed prior systemic chemotherapy.
Overall Study STARTED	46
Overall Study COMPLETED	43
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Intent-To-Treat Population Patients who enrolled and were scheduled to receive weekly topotecan (4 mg/m\^2 will be given as a 30-minute intravenous infusion on days 1, 8, and 15 with a rest on day 22 and repeated every 28 days) and bi-weekly Avastin (bevacizumab given by IV infusion at the dose of 10 mg/kg on days 1 and 15 after topotecan administration)in patients with non-small cell lung cancer (NSCLC) who have failed prior systemic chemotherapy.
Overall Study Insurance did not cover Avastin	1
Overall Study Screen failure	1
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Topotecan and Bevacizumab in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer That Did Not Respond to Previous Systemic Chemotherapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Intent-To-Treat Population n=46 Participants Patients who enrolled and were scheduled to receive weekly topotecan (4 mg/m\^2 will be given as a 30-minute intravenous infusion on days 1, 8, and 15 with a rest on day 22 and repeated every 28 days) and bi-weekly Avastin (bevacizumab given by IV infusion at the dose of 10 mg/kg on days 1 and 15 after topotecan administration)in patients with non-small cell lung cancer (NSCLC) who have failed prior systemic chemotherapy.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	26 Participants n=5 Participants
Age, Categorical >=65 years	20 Participants n=5 Participants
Age, Continuous	60.5 years STANDARD_DEVIATION 11.8 • n=5 Participants
Sex: Female, Male Female	25 Participants n=5 Participants
Sex: Female, Male Male	21 Participants n=5 Participants
Region of Enrollment United States	46 participants n=5 Participants

PRIMARY outcome

Timeframe: From Day 1 Until First Documented Disease Progression or Date of Death (Whichever Occurred First)

Population: All intent-to-treat patients enrolled were analyzed. Maximum number of days was 1349.

Outcome measures

Outcome measures
Measure	Intent-To-Treat Population n=46 Participants Patients who enrolled and were scheduled to receive weekly topotecan (4 mg/m\^2 will be given as a 30-minute intravenous infusion on days 1, 8, and 15 with a rest on day 22 and repeated every 28 days) and bi-weekly Avastin (bevacizumab) given by intravenous (IV) infusion at the dose of 10 mg/kg on days 1 and 15 after topotecan administration)in patients with non-small cell lung cancer (NSCLC) who have failed prior systemic chemotherapy.
Median Time to Disease Progression	152 Days Interval 112.0 to 233.0

SECONDARY outcome

Timeframe: From Day 1 Until Disease Progression or Date of Death (Whichever Occurred First), Up to 1 Year

Patients that met Solid Tumor Response Criteria (RECIST) criteria for partial response (at least a 30% decrease in the sum of the longest diameters of target lesions) and complete response (disappearance of all target lesions).

Outcome measures

Outcome measures
Measure	Intent-To-Treat Population n=41 Participants Patients who enrolled and were scheduled to receive weekly topotecan (4 mg/m\^2 will be given as a 30-minute intravenous infusion on days 1, 8, and 15 with a rest on day 22 and repeated every 28 days) and bi-weekly Avastin (bevacizumab) given by intravenous (IV) infusion at the dose of 10 mg/kg on days 1 and 15 after topotecan administration)in patients with non-small cell lung cancer (NSCLC) who have failed prior systemic chemotherapy.
Number of Tumor Responders Partial Response	6 Participants
Number of Tumor Responders Complete Response	0 Participants

SECONDARY outcome

Timeframe: From Day 1 Until Tumor Response

Population: Maximum number of days for analysis was 104.

Defined as the time from the start of treatment until first documented evidence of at least a partial tumor response.

Outcome measures

Outcome measures
Measure	Intent-To-Treat Population n=6 Participants Patients who enrolled and were scheduled to receive weekly topotecan (4 mg/m\^2 will be given as a 30-minute intravenous infusion on days 1, 8, and 15 with a rest on day 22 and repeated every 28 days) and bi-weekly Avastin (bevacizumab) given by intravenous (IV) infusion at the dose of 10 mg/kg on days 1 and 15 after topotecan administration)in patients with non-small cell lung cancer (NSCLC) who have failed prior systemic chemotherapy.
Median Time to Response	62.5 Days Interval 55.0 to 104.0

SECONDARY outcome

Timeframe: Day of 1st Response Until Disease Progression of Death/Last Contact

Population: Maximum number of days was 1277.

Defined to be the time from first documented evidence of response until the first documented sign of disease progression or death due to progressive disease. For subjects who do not progress or die, duration of response will be censored at the time of last contact.

Outcome measures

Outcome measures
Measure	Intent-To-Treat Population n=6 Participants Patients who enrolled and were scheduled to receive weekly topotecan (4 mg/m\^2 will be given as a 30-minute intravenous infusion on days 1, 8, and 15 with a rest on day 22 and repeated every 28 days) and bi-weekly Avastin (bevacizumab) given by intravenous (IV) infusion at the dose of 10 mg/kg on days 1 and 15 after topotecan administration)in patients with non-small cell lung cancer (NSCLC) who have failed prior systemic chemotherapy.
Median Duration of Response	186.5 Days Interval 105.0 to 1277.0

SECONDARY outcome

Timeframe: From Day 1 Until Death Occurred

Population: Maximum number of days was 1349.

Defined as the time from the start of treatment until death due to whatever cause. For subjects alive at study completion, time to death will be censored at the time of last contact.

Outcome measures

Outcome measures
Measure	Intent-To-Treat Population n=46 Participants Patients who enrolled and were scheduled to receive weekly topotecan (4 mg/m\^2 will be given as a 30-minute intravenous infusion on days 1, 8, and 15 with a rest on day 22 and repeated every 28 days) and bi-weekly Avastin (bevacizumab) given by intravenous (IV) infusion at the dose of 10 mg/kg on days 1 and 15 after topotecan administration)in patients with non-small cell lung cancer (NSCLC) who have failed prior systemic chemotherapy.
Median Overall Survival	345 Days Interval 213.0 to 464.0

Adverse Events

Safety Population

Serious events: 10 serious events

Other events: 36 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Safety Population n=43 participants at risk Patients who received treatment with weekly topotecan (4 mg/m\^2 will be given as a 30-minute intravenous infusion on days 1, 8, and 15 with a rest on day 22 and repeated every 28 days) and bi-weekly Avastin (bevacizumab given by IV infusion at the dose of 10 mg/kg on days 1 and 15 after topotecan administration)in patients with non-small cell lung cancer (NSCLC) who have failed prior systemic chemotherapy.
Musculoskeletal and connective tissue disorders Pain, muscle	2.3% 1/43 • Number of events 1 • Adverse events (AEs) were collected from Day 1 of treatment through 4 weeks post treatment. AEs were not collected for 3 patients who were enrolled but never received treatment.
General disorders Fatigue	2.3% 1/43 • Number of events 1 • Adverse events (AEs) were collected from Day 1 of treatment through 4 weeks post treatment. AEs were not collected for 3 patients who were enrolled but never received treatment.
General disorders Headache	4.7% 2/43 • Number of events 2 • Adverse events (AEs) were collected from Day 1 of treatment through 4 weeks post treatment. AEs were not collected for 3 patients who were enrolled but never received treatment.
Gastrointestinal disorders Nausea	2.3% 1/43 • Number of events 1 • Adverse events (AEs) were collected from Day 1 of treatment through 4 weeks post treatment. AEs were not collected for 3 patients who were enrolled but never received treatment.
Infections and infestations Infection with normal ANC or G1/2 neutrophils-blood	2.3% 1/43 • Number of events 1 • Adverse events (AEs) were collected from Day 1 of treatment through 4 weeks post treatment. AEs were not collected for 3 patients who were enrolled but never received treatment.
Infections and infestations Infection with normal ANC or G1/2 neutrophils - lung	2.3% 1/43 • Number of events 1 • Adverse events (AEs) were collected from Day 1 of treatment through 4 weeks post treatment. AEs were not collected for 3 patients who were enrolled but never received treatment.
General disorders Fever in absence of neutropenia	2.3% 1/43 • Number of events 1 • Adverse events (AEs) were collected from Day 1 of treatment through 4 weeks post treatment. AEs were not collected for 3 patients who were enrolled but never received treatment.
General disorders Progressive disease	2.3% 1/43 • Number of events 1 • Adverse events (AEs) were collected from Day 1 of treatment through 4 weeks post treatment. AEs were not collected for 3 patients who were enrolled but never received treatment.
General disorders Death	2.3% 1/43 • Number of events 1 • Adverse events (AEs) were collected from Day 1 of treatment through 4 weeks post treatment. AEs were not collected for 3 patients who were enrolled but never received treatment.
Gastrointestinal disorders Dehydration	2.3% 1/43 • Number of events 1 • Adverse events (AEs) were collected from Day 1 of treatment through 4 weeks post treatment. AEs were not collected for 3 patients who were enrolled but never received treatment.
Respiratory, thoracic and mediastinal disorders Pneumonitis	2.3% 1/43 • Number of events 1 • Adverse events (AEs) were collected from Day 1 of treatment through 4 weeks post treatment. AEs were not collected for 3 patients who were enrolled but never received treatment.
Blood and lymphatic system disorders Hemorrhage, pulmonary	2.3% 1/43 • Number of events 1 • Adverse events (AEs) were collected from Day 1 of treatment through 4 weeks post treatment. AEs were not collected for 3 patients who were enrolled but never received treatment.
General disorders Pain, pleura	2.3% 1/43 • Number of events 1 • Adverse events (AEs) were collected from Day 1 of treatment through 4 weeks post treatment. AEs were not collected for 3 patients who were enrolled but never received treatment.
General disorders Pain, abdomen	2.3% 1/43 • Number of events 1 • Adverse events (AEs) were collected from Day 1 of treatment through 4 weeks post treatment. AEs were not collected for 3 patients who were enrolled but never received treatment.
Gastrointestinal disorders Obstruction, small bowel	2.3% 1/43 • Number of events 1 • Adverse events (AEs) were collected from Day 1 of treatment through 4 weeks post treatment. AEs were not collected for 3 patients who were enrolled but never received treatment.
General disorders Pain, chest wall	2.3% 1/43 • Number of events 1 • Adverse events (AEs) were collected from Day 1 of treatment through 4 weeks post treatment. AEs were not collected for 3 patients who were enrolled but never received treatment.
Respiratory, thoracic and mediastinal disorders Hypoxia	2.3% 1/43 • Number of events 1 • Adverse events (AEs) were collected from Day 1 of treatment through 4 weeks post treatment. AEs were not collected for 3 patients who were enrolled but never received treatment.
Respiratory, thoracic and mediastinal disorders Dyspnea	2.3% 1/43 • Number of events 1 • Adverse events (AEs) were collected from Day 1 of treatment through 4 weeks post treatment. AEs were not collected for 3 patients who were enrolled but never received treatment.
Cardiac disorders Atrial fibrillation	2.3% 1/43 • Number of events 1 • Adverse events (AEs) were collected from Day 1 of treatment through 4 weeks post treatment. AEs were not collected for 3 patients who were enrolled but never received treatment.
Musculoskeletal and connective tissue disorders Pain, bone	2.3% 1/43 • Number of events 1 • Adverse events (AEs) were collected from Day 1 of treatment through 4 weeks post treatment. AEs were not collected for 3 patients who were enrolled but never received treatment.
Musculoskeletal and connective tissue disorders Pain, joint	2.3% 1/43 • Number of events 1 • Adverse events (AEs) were collected from Day 1 of treatment through 4 weeks post treatment. AEs were not collected for 3 patients who were enrolled but never received treatment.
Nervous system disorders Seizure	2.3% 1/43 • Number of events 1 • Adverse events (AEs) were collected from Day 1 of treatment through 4 weeks post treatment. AEs were not collected for 3 patients who were enrolled but never received treatment.

Other adverse events

Other adverse events
Measure	Safety Population n=43 participants at risk Patients who received treatment with weekly topotecan (4 mg/m\^2 will be given as a 30-minute intravenous infusion on days 1, 8, and 15 with a rest on day 22 and repeated every 28 days) and bi-weekly Avastin (bevacizumab given by IV infusion at the dose of 10 mg/kg on days 1 and 15 after topotecan administration)in patients with non-small cell lung cancer (NSCLC) who have failed prior systemic chemotherapy.
Musculoskeletal and connective tissue disorders Achy, muscle aches	7.0% 3/43 • Number of events 3 • Adverse events (AEs) were collected from Day 1 of treatment through 4 weeks post treatment. AEs were not collected for 3 patients who were enrolled but never received treatment.
Blood and lymphatic system disorders Anemia	25.6% 11/43 • Number of events 25 • Adverse events (AEs) were collected from Day 1 of treatment through 4 weeks post treatment. AEs were not collected for 3 patients who were enrolled but never received treatment.
Gastrointestinal disorders Diarrhea	16.3% 7/43 • Number of events 7 • Adverse events (AEs) were collected from Day 1 of treatment through 4 weeks post treatment. AEs were not collected for 3 patients who were enrolled but never received treatment.
General disorders Fatigue	39.5% 17/43 • Number of events 28 • Adverse events (AEs) were collected from Day 1 of treatment through 4 weeks post treatment. AEs were not collected for 3 patients who were enrolled but never received treatment.
General disorders Headache	27.9% 12/43 • Number of events 13 • Adverse events (AEs) were collected from Day 1 of treatment through 4 weeks post treatment. AEs were not collected for 3 patients who were enrolled but never received treatment.
Infections and infestations Upper respiratory infection	7.0% 3/43 • Number of events 4 • Adverse events (AEs) were collected from Day 1 of treatment through 4 weeks post treatment. AEs were not collected for 3 patients who were enrolled but never received treatment.
General disorders Malaise	7.0% 3/43 • Number of events 12 • Adverse events (AEs) were collected from Day 1 of treatment through 4 weeks post treatment. AEs were not collected for 3 patients who were enrolled but never received treatment.
Blood and lymphatic system disorders Neutropenia	14.0% 6/43 • Number of events 8 • Adverse events (AEs) were collected from Day 1 of treatment through 4 weeks post treatment. AEs were not collected for 3 patients who were enrolled but never received treatment.
Gastrointestinal disorders Nausea	39.5% 17/43 • Number of events 20 • Adverse events (AEs) were collected from Day 1 of treatment through 4 weeks post treatment. AEs were not collected for 3 patients who were enrolled but never received treatment.
Musculoskeletal and connective tissue disorders Back pain	14.0% 6/43 • Number of events 6 • Adverse events (AEs) were collected from Day 1 of treatment through 4 weeks post treatment. AEs were not collected for 3 patients who were enrolled but never received treatment.
Musculoskeletal and connective tissue disorders Rib pain	7.0% 3/43 • Number of events 3 • Adverse events (AEs) were collected from Day 1 of treatment through 4 weeks post treatment. AEs were not collected for 3 patients who were enrolled but never received treatment.
Gastrointestinal disorders Abdominal pain	7.0% 3/43 • Number of events 3 • Adverse events (AEs) were collected from Day 1 of treatment through 4 weeks post treatment. AEs were not collected for 3 patients who were enrolled but never received treatment.
General disorders Chest pain	7.0% 3/43 • Number of events 3 • Adverse events (AEs) were collected from Day 1 of treatment through 4 weeks post treatment. AEs were not collected for 3 patients who were enrolled but never received treatment.
Musculoskeletal and connective tissue disorders Shoulder pain	14.0% 6/43 • Number of events 6 • Adverse events (AEs) were collected from Day 1 of treatment through 4 weeks post treatment. AEs were not collected for 3 patients who were enrolled but never received treatment.
Skin and subcutaneous tissue disorders Rash	7.0% 3/43 • Number of events 3 • Adverse events (AEs) were collected from Day 1 of treatment through 4 weeks post treatment. AEs were not collected for 3 patients who were enrolled but never received treatment.
Respiratory, thoracic and mediastinal disorders Congestion, sinus/nasal	7.0% 3/43 • Number of events 3 • Adverse events (AEs) were collected from Day 1 of treatment through 4 weeks post treatment. AEs were not collected for 3 patients who were enrolled but never received treatment.
Blood and lymphatic system disorders Thrombocytopenia	39.5% 17/43 • Number of events 31 • Adverse events (AEs) were collected from Day 1 of treatment through 4 weeks post treatment. AEs were not collected for 3 patients who were enrolled but never received treatment.
Gastrointestinal disorders Vomiting	11.6% 5/43 • Number of events 9 • Adverse events (AEs) were collected from Day 1 of treatment through 4 weeks post treatment. AEs were not collected for 3 patients who were enrolled but never received treatment.
Respiratory, thoracic and mediastinal disorders Cough	34.9% 15/43 • Number of events 18 • Adverse events (AEs) were collected from Day 1 of treatment through 4 weeks post treatment. AEs were not collected for 3 patients who were enrolled but never received treatment.
Gastrointestinal disorders Epitaxis	7.0% 3/43 • Number of events 5 • Adverse events (AEs) were collected from Day 1 of treatment through 4 weeks post treatment. AEs were not collected for 3 patients who were enrolled but never received treatment.
Respiratory, thoracic and mediastinal disorders Dyspnea, shortness of breath	16.3% 7/43 • Number of events 11 • Adverse events (AEs) were collected from Day 1 of treatment through 4 weeks post treatment. AEs were not collected for 3 patients who were enrolled but never received treatment.

Additional Information

Arkadiusz Dudek, M.D.

Masonic Cancer Center, University of Minnesota

Phone: 612-624-0123

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place