Trial Outcomes & Findings for Paclitaxel With or Without Cixutumumab as Second-Line Therapy in Treating Patients With Metastatic Esophageal Cancer or Gastroesophageal Junction Cancer (NCT NCT01142388)

Last Updated: 2025-11-25

Results Overview

Progression-free survival (PFS) is defined as the time from randomization to progression or death without evidence of progression. For cases without documentation of progression, follow-up was censored at the date of last disease assessment without progression, unless death occurred within a short period of time (4 months) following the date last known progression-free, in which case the death was counted as an event, or in the case of death within 4 months of randomization in the absence of disease evaluation before that time. PFS was estimated using the Kaplan-Meier method, with 90% confidence intervals calculated using Greenwood's formula, and compared by the log rank test.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

94 participants

Primary outcome timeframe

assessed every 3 months for 2 years after registration

Results posted on

2025-11-25

Participant Flow

This study was activated on September 21, 2010 and closed to accrual on October 15, 2012 with total accrual of 94 patients from 27 ECOG-ACRIN affiliated institutions.

Participant milestones

Participant milestones
Measure	Arm I (Paclitaxel) Patients receive paclitaxel IV over 1 hour at a dose of 80 mg/m\^2 on days 1, 8, and 15 of every 28 day cycle. paclitaxel: Given IV	Arm II (Cixutumumab, Paclitaxel) Patients receive cixutumumab IV over 1 hour at a dose of 10 mg/kg on days 1 and 15 of every 28 day cycle, and paclitaxel as in Arm I. cixutumumab: Given IV, administered prior to chemotherapy, doses were based on actual body weight paclitaxel: Given IV
Overall Study STARTED	47	47
Overall Study Eligible	43	44
Overall Study Treated	40	44
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	47	47

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm I (Paclitaxel) Patients receive paclitaxel IV over 1 hour at a dose of 80 mg/m\^2 on days 1, 8, and 15 of every 28 day cycle. paclitaxel: Given IV	Arm II (Cixutumumab, Paclitaxel) Patients receive cixutumumab IV over 1 hour at a dose of 10 mg/kg on days 1 and 15 of every 28 day cycle, and paclitaxel as in Arm I. cixutumumab: Given IV, administered prior to chemotherapy, doses were based on actual body weight paclitaxel: Given IV
Overall Study Lack of Efficacy	21	31
Overall Study Adverse Event	9	5
Overall Study Death	3	2
Overall Study Withdrawal by Subject	5	3
Overall Study Alternative therapy	1	0
Overall Study Other complications	0	2
Overall Study Other	1	1
Overall Study Never started therapy	7	3

Baseline Characteristics

Paclitaxel With or Without Cixutumumab as Second-Line Therapy in Treating Patients With Metastatic Esophageal Cancer or Gastroesophageal Junction Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I (Paclitaxel) n=43 Participants Patients receive paclitaxel IV over 1 hour at a dose of 80 mg/m\^2 on days 1, 8, and 15 of every 28 day cycle. paclitaxel: Given IV	Arm II (Cixutumumab, Paclitaxel) n=44 Participants Patients receive cixutumumab IV over 1 hour at a dose of 10 mg/kg on days 1 and 15 of every 28 day cycle, and paclitaxel as in Arm I. cixutumumab: Given IV, administered prior to chemotherapy, doses were based on actual body weight paclitaxel: Given IV	Total n=87 Participants Total of all reporting groups
Age, Continuous	63 years n=45 Participants	62 years n=12929 Participants	62 years n=6349 Participants
Sex: Female, Male Female	8 Participants n=45 Participants	11 Participants n=12929 Participants	19 Participants n=6349 Participants
Sex: Female, Male Male	35 Participants n=45 Participants	33 Participants n=12929 Participants	68 Participants n=6349 Participants
Region of Enrollment United States	43 participants n=45 Participants	44 participants n=12929 Participants	87 participants n=6349 Participants

PRIMARY outcome

Timeframe: assessed every 3 months for 2 years after registration

Population: Eligible patients.

Outcome measures

Outcome measures
Measure	Arm I (Paclitaxel) n=43 Participants Patients receive paclitaxel IV over 1 hour at a dose of 80 mg/m\^2 on days 1, 8, and 15 of every 28 day cycle. paclitaxel: Given IV	Arm II (Cixutumumab, Paclitaxel) n=44 Participants Patients receive cixutumumab IV over 1 hour at a dose of 10 mg/kg on days 1 and 15 of every 28 day cycle, and paclitaxel as in Arm I. cixutumumab: Given IV, administered prior to chemotherapy, doses were based on actual body weight paclitaxel: Given IV
Progression-free Survival	2.6 months Interval 1.8 to 4.1	2.3 months Interval 2.0 to 3.6

SECONDARY outcome

Timeframe: assessed every 3 months for 2 years after registration

Population: Eligible patients

Overall survival (OS) is defined as the time from randomization until death (event), or censored at last date known alive. OS was estimated using the Kaplan-Meier method, with 90% confidence intervals calculated using Greenwood's formula, and compared by the log rank test.

Outcome measures

Outcome measures
Measure	Arm I (Paclitaxel) n=43 Participants Patients receive paclitaxel IV over 1 hour at a dose of 80 mg/m\^2 on days 1, 8, and 15 of every 28 day cycle. paclitaxel: Given IV	Arm II (Cixutumumab, Paclitaxel) n=44 Participants Patients receive cixutumumab IV over 1 hour at a dose of 10 mg/kg on days 1 and 15 of every 28 day cycle, and paclitaxel as in Arm I. cixutumumab: Given IV, administered prior to chemotherapy, doses were based on actual body weight paclitaxel: Given IV
Overall Survival	6.5 months Interval 4.6 to 9.5	6.4 months Interval 4.9 to 8.0

SECONDARY outcome

Timeframe: assessed every 8 weeks while on treatment and every 3 months after treatment for 2 years

Population: Eligible patients

Objective response rate is defined as number of patients with complete response (CR) or partial response (PR) divided by all eligible patients. Responses are evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline. CR is defined as disappearance of all target and non-target lesions and normalization of tumor marker level. PR is defined as disappearance of target lesions or at least a 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameters), and persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits.

Outcome measures

Outcome measures
Measure	Arm I (Paclitaxel) n=43 Participants Patients receive paclitaxel IV over 1 hour at a dose of 80 mg/m\^2 on days 1, 8, and 15 of every 28 day cycle. paclitaxel: Given IV	Arm II (Cixutumumab, Paclitaxel) n=44 Participants Patients receive cixutumumab IV over 1 hour at a dose of 10 mg/kg on days 1 and 15 of every 28 day cycle, and paclitaxel as in Arm I. cixutumumab: Given IV, administered prior to chemotherapy, doses were based on actual body weight paclitaxel: Given IV
Objective Response Rate	12 percentage of participants Interval 5.0 to 23.0	14 percentage of participants Interval 6.0 to 25.0

Adverse Events

Arm I (Paclitaxel)

Serious events: 21 serious events

Other events: 39 other events

Deaths: 0 deaths

Arm II (Cixutumumab, Paclitaxel)

Serious events: 23 serious events

Other events: 43 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Statistician

ECOG-ACRIN Statistical Office

Phone: 617-632-3012

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Serious adverse events
Measure	Arm I (Paclitaxel) n=40 participants at risk Patients receive paclitaxel IV over 1 hour at a dose of 80 mg/m\^2 on days 1, 8, and 15 of every 28 day cycle. paclitaxel: Given IV	Arm II (Cixutumumab, Paclitaxel) n=44 participants at risk Patients receive cixutumumab IV over 1 hour at a dose of 10 mg/kg on days 1 and 15 of every 28 day cycle, and paclitaxel as in Arm I. cixutumumab: Given IV, administered prior to chemotherapy, doses were based on actual body weight paclitaxel: Given IV
Blood and lymphatic system disorders Anemia	10.0% 4/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	9.1% 4/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Blood and lymphatic system disorders Leukocytosis	2.5% 1/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	2.3% 1/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Cardiac disorders Atrial fibrillation	0.00% 0/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	2.3% 1/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Cardiac disorders Left ventricular systolic dysfunction	0.00% 0/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	2.3% 1/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
General disorders Death NOS	2.5% 1/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	0.00% 0/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
General disorders Fatigue	10.0% 4/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	2.3% 1/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
General disorders Infusion related reaction	2.5% 1/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	0.00% 0/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Skin and subcutaneous tissue disorders Rash maculo-papular	2.5% 1/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	0.00% 0/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Gastrointestinal disorders Abdominal pain	2.5% 1/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	0.00% 0/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Gastrointestinal disorders Gastric perforation	2.5% 1/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	0.00% 0/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Gastrointestinal disorders Mucositis oral	0.00% 0/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	4.5% 2/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Gastrointestinal disorders Nausea	2.5% 1/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	2.3% 1/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Gastrointestinal disorders Upper gastrointestinal hemorrhage	2.5% 1/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	0.00% 0/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Gastrointestinal disorders Vomiting	0.00% 0/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	4.5% 2/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Infections and infestations Sepsis	2.5% 1/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	0.00% 0/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Investigations Alkaline phosphatase increased	2.5% 1/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	0.00% 0/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Investigations Aspartate aminotransferase increased	2.5% 1/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	0.00% 0/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Investigations Blood bilirubin increased	2.5% 1/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	0.00% 0/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Investigations Lymphocyte count decreased	20.0% 8/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	18.2% 8/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Investigations Neutrophil count decreased	7.5% 3/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	18.2% 8/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Investigations Platelet count decreased	0.00% 0/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	2.3% 1/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Investigations Weight loss	0.00% 0/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	2.3% 1/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Investigations White blood cell decreased	5.0% 2/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	13.6% 6/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Metabolism and nutrition disorders Dehydration	0.00% 0/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	2.3% 1/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Metabolism and nutrition disorders Glucose intolerance	0.00% 0/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	2.3% 1/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Metabolism and nutrition disorders Hyperglycemia	5.0% 2/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	11.4% 5/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Metabolism and nutrition disorders Hypokalemia	2.5% 1/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	0.00% 0/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Metabolism and nutrition disorders Hyponatremia	0.00% 0/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	2.3% 1/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Metabolism and nutrition disorders Hypophosphatemia	5.0% 2/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	2.3% 1/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	0.00% 0/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	4.5% 2/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Musculoskeletal and connective tissue disorders Myalgia	2.5% 1/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	0.00% 0/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Musculoskeletal and connective tissue disorders Neck pain	2.5% 1/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	0.00% 0/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Nervous system disorders Peripheral motor neuropathy	0.00% 0/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	2.3% 1/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Nervous system disorders Peripheral sensory neuropathy	2.5% 1/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	2.3% 1/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Nervous system disorders Syncope	2.5% 1/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	0.00% 0/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	2.3% 1/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Respiratory, thoracic and mediastinal disorders Pneumonitis	2.5% 1/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	0.00% 0/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	2.3% 1/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Vascular disorders Hypertension	0.00% 0/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	2.3% 1/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Vascular disorders Hypotension	0.00% 0/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	2.3% 1/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.

Other adverse events
Measure	Arm I (Paclitaxel) n=40 participants at risk Patients receive paclitaxel IV over 1 hour at a dose of 80 mg/m\^2 on days 1, 8, and 15 of every 28 day cycle. paclitaxel: Given IV	Arm II (Cixutumumab, Paclitaxel) n=44 participants at risk Patients receive cixutumumab IV over 1 hour at a dose of 10 mg/kg on days 1 and 15 of every 28 day cycle, and paclitaxel as in Arm I. cixutumumab: Given IV, administered prior to chemotherapy, doses were based on actual body weight paclitaxel: Given IV
Blood and lymphatic system disorders Anemia	72.5% 29/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	65.9% 29/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
General disorders Edema limbs	10.0% 4/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	2.3% 1/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
General disorders Fatigue	67.5% 27/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	61.4% 27/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Skin and subcutaneous tissue disorders Alopecia	32.5% 13/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	27.3% 12/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Skin and subcutaneous tissue disorders Pruritus	7.5% 3/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	11.4% 5/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Skin and subcutaneous tissue disorders Rash acneiform	2.5% 1/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	11.4% 5/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Skin and subcutaneous tissue disorders Rash maculo-papular	5.0% 2/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	18.2% 8/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Gastrointestinal disorders Constipation	10.0% 4/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	4.5% 2/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Gastrointestinal disorders Diarrhea	20.0% 8/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	22.7% 10/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Gastrointestinal disorders Mucositis oral	5.0% 2/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	11.4% 5/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Gastrointestinal disorders Nausea	20.0% 8/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	31.8% 14/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Gastrointestinal disorders Vomiting	15.0% 6/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	20.5% 9/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Investigations Alanine aminotransferase increased	12.5% 5/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	9.1% 4/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Investigations Alkaline phosphatase increased	12.5% 5/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	22.7% 10/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Investigations Aspartate aminotransferase increased	12.5% 5/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	18.2% 8/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Investigations Creatinine increased	0.00% 0/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	9.1% 4/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Investigations Lymphocyte count decreased	42.5% 17/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	34.1% 15/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Investigations Neutrophil count decreased	25.0% 10/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	31.8% 14/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Investigations Platelet count decreased	15.0% 6/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	22.7% 10/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Investigations Weight loss	20.0% 8/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	18.2% 8/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Investigations White blood cell decreased	32.5% 13/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	40.9% 18/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Metabolism and nutrition disorders Anorexia	17.5% 7/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	27.3% 12/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Metabolism and nutrition disorders Glucose intolerance	7.5% 3/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	11.4% 5/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Metabolism and nutrition disorders Hyperglycemia	22.5% 9/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	38.6% 17/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Metabolism and nutrition disorders Hypoalbuminemia	7.5% 3/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	9.1% 4/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Metabolism and nutrition disorders Hypocalcemia	0.00% 0/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	11.4% 5/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Metabolism and nutrition disorders Hypokalemia	7.5% 3/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	6.8% 3/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Metabolism and nutrition disorders Hypomagnesemia	12.5% 5/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	13.6% 6/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Metabolism and nutrition disorders Hyponatremia	7.5% 3/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	18.2% 8/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Metabolism and nutrition disorders Hypophosphatemia	7.5% 3/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	4.5% 2/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Musculoskeletal and connective tissue disorders Arthralgia	2.5% 1/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	6.8% 3/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Musculoskeletal and connective tissue disorders Myalgia	2.5% 1/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	11.4% 5/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	9.1% 4/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Nervous system disorders Dizziness	5.0% 2/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	11.4% 5/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Nervous system disorders Dysgeusia	2.5% 1/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	11.4% 5/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Nervous system disorders Headache	2.5% 1/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	9.1% 4/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Nervous system disorders Paresthesia	7.5% 3/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	0.00% 0/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Nervous system disorders Peripheral sensory neuropathy	35.0% 14/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	36.4% 16/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Eye disorders Flashing lights	0.00% 0/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	15.9% 7/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.
Eye disorders Floaters	0.00% 0/40 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.	6.8% 3/44 • Assessed at the end of each cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.