Trial Outcomes & Findings for Nab-Paclitaxel and Bevacizumab or Ipilimumab as First-Line Therapy in Treating Patients With Stage IV Melanoma That Cannot Be Removed by Surgery (NCT NCT02158520)

Last Updated: 2020-01-21

Results Overview

Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study or a measurable increase in a non-target lesion, or the appearance of new lesions.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

24 participants

Primary outcome timeframe

From randomization to the earliest documentation of progression as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria (version 1.1) or death from any cause without the documentation of progression, assessed up to 4 years

Results posted on

2020-01-21

Participant Flow

This study was closed to enroll on November 19, 2015 after having enrolled 24 patients (12 patients per arm) due to the FDA approval of new agents for this patient population.

Participant milestones

Participant milestones
Measure	Arm A (Bevacizumab and Nab-paclitaxel) Patients receive bevacizumab 10mg/kg IV over 30-90 minutes on days 1 and 15 and nab-paclitaxel 150 mg/m\^2 IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients experiencing progressive disease may cross-over to Arm B within 2-4 weeks.	Arm B (Ipilimumab) Patients receive ipilimumab 3 mg/kg IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients experiencing progressive disease may cross-over to Arm A within 2-4 weeks.
Overall Study STARTED	12	12
Overall Study AE Evaluated Prior to Crossover	12	12
Overall Study Eligible for Crossover	8	8
Overall Study Eligible for Crossover With AE Evaluated	7	7
Overall Study Crossover Cohort	4	6
Overall Study COMPLETED	12	12
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Nab-Paclitaxel and Bevacizumab or Ipilimumab as First-Line Therapy in Treating Patients With Stage IV Melanoma That Cannot Be Removed by Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A (Bevacizumab and Nab-paclitaxel) n=12 Participants Patients receive bevacizumab 10mg/kg IV over 30-90 minutes on days 1 and 15 and nab-paclitaxel 150 mg/m\^2 IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients experiencing progressive disease may cross-over to Arm B within 2-4 weeks.	Arm B (Ipilimumab) n=12 Participants Patients receive ipilimumab 3 mg/kg IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients experiencing progressive disease may cross-over to Arm A within 2-4 weeks.	Total n=24 Participants Total of all reporting groups
Age, Continuous	60 years n=99 Participants	61 years n=107 Participants	61 years n=206 Participants
Sex/Gender, Customized Sex/Gender · Male	8 Participants n=99 Participants	7 Participants n=107 Participants	15 Participants n=206 Participants
Sex/Gender, Customized Sex/Gender · Female	4 Participants n=99 Participants	4 Participants n=107 Participants	8 Participants n=206 Participants
Sex/Gender, Customized Sex/Gender · Unknown	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) White	12 Participants n=99 Participants	12 Participants n=107 Participants	24 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Prior radiation therapy	4 Participants n=99 Participants	3 Participants n=107 Participants	7 Participants n=206 Participants

PRIMARY outcome

Timeframe: From randomization to the earliest documentation of progression as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria (version 1.1) or death from any cause without the documentation of progression, assessed up to 4 years

Outcome measures

Outcome measures
Measure	Arm A (Bevacizumab and Nab-paclitaxel) n=12 Participants Patients receive bevacizumab 10mg/kg IV over 30-90 minutes on days 1 and 15 and nab-paclitaxel 150 mg/m\^2 IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients experiencing progressive disease may cross-over to Arm B within 2-4 weeks.	Arm B (Ipilimumab) n=12 Participants Patients receive ipilimumab 3 mg/kg IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients experiencing progressive disease may cross-over to Arm A within 2-4 weeks.
Progression-free Survival (PFS)	139 days Interval 86.0 to The 95% confidence interval upper limit was not reached (below the level of detection).	94 days Interval 74.0 to The 95% confidence interval upper limit was not reached (below the level of detection).

SECONDARY outcome

Timeframe: From registration to death due to any cause, assessed up to 4 years

Overall survival time is defined as the time from randomization to death due to any cause. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.

Outcome measures

Outcome measures
Measure	Arm A (Bevacizumab and Nab-paclitaxel) n=12 Participants Patients receive bevacizumab 10mg/kg IV over 30-90 minutes on days 1 and 15 and nab-paclitaxel 150 mg/m\^2 IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients experiencing progressive disease may cross-over to Arm B within 2-4 weeks.	Arm B (Ipilimumab) n=12 Participants Patients receive ipilimumab 3 mg/kg IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients experiencing progressive disease may cross-over to Arm A within 2-4 weeks.
Overall Survival (OS)	18.4 months Interval 11.4 to The 95% confidence interval upper limit was not reached (below the level of detection).	27.0 months Interval 11.3 to The 95% confidence interval upper limit was not reached (below the level of detection).

SECONDARY outcome

Timeframe: Up to 4 years

Tumor response defined as complete or partial response using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Complete response (CR): Disappearance of all evidence of disease, Partial response (PR): Regression of measurable disease and no new sites.

Outcome measures

Outcome measures
Measure	Arm A (Bevacizumab and Nab-paclitaxel) n=12 Participants Patients receive bevacizumab 10mg/kg IV over 30-90 minutes on days 1 and 15 and nab-paclitaxel 150 mg/m\^2 IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients experiencing progressive disease may cross-over to Arm B within 2-4 weeks.	Arm B (Ipilimumab) n=12 Participants Patients receive ipilimumab 3 mg/kg IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients experiencing progressive disease may cross-over to Arm A within 2-4 weeks.
Number of Patients With Tumor Response CR	2 Participants	0 Participants
Number of Patients With Tumor Response PR	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to 4 years

The number of patients who experienced toxicity (grade 3 or higher adverse events considered at least possibly related to treatment) are reported below.

Outcome measures

Outcome measures
Measure	Arm A (Bevacizumab and Nab-paclitaxel) n=12 Participants Patients receive bevacizumab 10mg/kg IV over 30-90 minutes on days 1 and 15 and nab-paclitaxel 150 mg/m\^2 IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients experiencing progressive disease may cross-over to Arm B within 2-4 weeks.	Arm B (Ipilimumab) n=12 Participants Patients receive ipilimumab 3 mg/kg IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients experiencing progressive disease may cross-over to Arm A within 2-4 weeks.
The Number of Patients Who Experienced Toxicity	9 Participants	7 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to up to 5 years

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to up to 5 years

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, prior to the end of paclitaxel albumin-stabilized nanoparticle formulation infusion, and the morning after nab-paclitaxel infusion on days 1 and 8 of course 1

Outcome measures

Outcome data not reported

Adverse Events

Arm A (Bevacizumab and Nab-paclitaxel)

Serious events: 2 serious events

Other events: 11 other events

Deaths: 10 deaths

Arm B (Ipilimumab)

Serious events: 4 serious events

Other events: 9 other events

Deaths: 8 deaths

Arm A Eligible for Crossover

Serious events: 2 serious events

Other events: 7 other events

Deaths: 6 deaths

Arm B Eligible for Crossover

Serious events: 2 serious events

Other events: 7 other events

Deaths: 5 deaths

Serious adverse events

Serious adverse events
Measure	Arm A (Bevacizumab and Nab-paclitaxel) n=12 participants at risk Patients receive bevacizumab 10mg/kg IV over 30-90 minutes on days 1 and 15 and nab-paclitaxel 150 mg/m\^2 IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients experiencing progressive disease may cross-over to Arm B within 2-4 weeks.	Arm B (Ipilimumab) n=12 participants at risk Patients receive ipilimumab 3 mg/kg IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients experiencing progressive disease may cross-over to Arm A within 2-4 weeks.	Arm A Eligible for Crossover n=7 participants at risk Arm A patients who experienced progressive disease and eligible for crossover to Arm B AND evaluated for adverse events.	Arm B Eligible for Crossover n=7 participants at risk Arm B patients who experienced progressive disease and eligible for crossover to Arm A AND evaluated for adverse events.
Blood and lymphatic system disorders Hemolytic uremic syndrome	8.3% 1/12 • Number of events 1 • Up to 4 years Adverse events are reported for each arm group (i.e. Arm A, Arm B, Arm A Eligible for Crossover, and Arm B Eligible for Crossover)	0.00% 0/12 • Up to 4 years Adverse events are reported for each arm group (i.e. Arm A, Arm B, Arm A Eligible for Crossover, and Arm B Eligible for Crossover)	14.3% 1/7 • Number of events 1 • Up to 4 years Adverse events are reported for each arm group (i.e. Arm A, Arm B, Arm A Eligible for Crossover, and Arm B Eligible for Crossover)	0.00% 0/7 • Up to 4 years Adverse events are reported for each arm group (i.e. Arm A, Arm B, Arm A Eligible for Crossover, and Arm B Eligible for Crossover)
Gastrointestinal disorders Rectal hemorrhage	8.3% 1/12 • Number of events 1 • Up to 4 years Adverse events are reported for each arm group (i.e. Arm A, Arm B, Arm A Eligible for Crossover, and Arm B Eligible for Crossover)	0.00% 0/12 • Up to 4 years Adverse events are reported for each arm group (i.e. Arm A, Arm B, Arm A Eligible for Crossover, and Arm B Eligible for Crossover)	0.00% 0/7 • Up to 4 years Adverse events are reported for each arm group (i.e. Arm A, Arm B, Arm A Eligible for Crossover, and Arm B Eligible for Crossover)	0.00% 0/7 • Up to 4 years Adverse events are reported for each arm group (i.e. Arm A, Arm B, Arm A Eligible for Crossover, and Arm B Eligible for Crossover)
Injury, poisoning and procedural complications Wound dehiscence	0.00% 0/12 • Up to 4 years Adverse events are reported for each arm group (i.e. Arm A, Arm B, Arm A Eligible for Crossover, and Arm B Eligible for Crossover)	0.00% 0/12 • Up to 4 years Adverse events are reported for each arm group (i.e. Arm A, Arm B, Arm A Eligible for Crossover, and Arm B Eligible for Crossover)	0.00% 0/7 • Up to 4 years Adverse events are reported for each arm group (i.e. Arm A, Arm B, Arm A Eligible for Crossover, and Arm B Eligible for Crossover)	14.3% 1/7 • Number of events 1 • Up to 4 years Adverse events are reported for each arm group (i.e. Arm A, Arm B, Arm A Eligible for Crossover, and Arm B Eligible for Crossover)
Investigations Creatinine increased	0.00% 0/12 • Up to 4 years Adverse events are reported for each arm group (i.e. Arm A, Arm B, Arm A Eligible for Crossover, and Arm B Eligible for Crossover)	0.00% 0/12 • Up to 4 years Adverse events are reported for each arm group (i.e. Arm A, Arm B, Arm A Eligible for Crossover, and Arm B Eligible for Crossover)	14.3% 1/7 • Number of events 1 • Up to 4 years Adverse events are reported for each arm group (i.e. Arm A, Arm B, Arm A Eligible for Crossover, and Arm B Eligible for Crossover)	0.00% 0/7 • Up to 4 years Adverse events are reported for each arm group (i.e. Arm A, Arm B, Arm A Eligible for Crossover, and Arm B Eligible for Crossover)
Investigations Lymphocyte count decreased	0.00% 0/12 • Up to 4 years Adverse events are reported for each arm group (i.e. Arm A, Arm B, Arm A Eligible for Crossover, and Arm B Eligible for Crossover)	8.3% 1/12 • Number of events 1 • Up to 4 years Adverse events are reported for each arm group (i.e. Arm A, Arm B, Arm A Eligible for Crossover, and Arm B Eligible for Crossover)	0.00% 0/7 • Up to 4 years Adverse events are reported for each arm group (i.e. Arm A, Arm B, Arm A Eligible for Crossover, and Arm B Eligible for Crossover)	0.00% 0/7 • Up to 4 years Adverse events are reported for each arm group (i.e. Arm A, Arm B, Arm A Eligible for Crossover, and Arm B Eligible for Crossover)
Investigations Platelet count decreased	0.00% 0/12 • Up to 4 years Adverse events are reported for each arm group (i.e. Arm A, Arm B, Arm A Eligible for Crossover, and Arm B Eligible for Crossover)	0.00% 0/12 • Up to 4 years Adverse events are reported for each arm group (i.e. Arm A, Arm B, Arm A Eligible for Crossover, and Arm B Eligible for Crossover)	14.3% 1/7 • Number of events 1 • Up to 4 years Adverse events are reported for each arm group (i.e. Arm A, Arm B, Arm A Eligible for Crossover, and Arm B Eligible for Crossover)	0.00% 0/7 • Up to 4 years Adverse events are reported for each arm group (i.e. Arm A, Arm B, Arm A Eligible for Crossover, and Arm B Eligible for Crossover)
Metabolism and nutrition disorders Dehydration	0.00% 0/12 • Up to 4 years Adverse events are reported for each arm group (i.e. Arm A, Arm B, Arm A Eligible for Crossover, and Arm B Eligible for Crossover)	0.00% 0/12 • Up to 4 years Adverse events are reported for each arm group (i.e. Arm A, Arm B, Arm A Eligible for Crossover, and Arm B Eligible for Crossover)	14.3% 1/7 • Number of events 1 • Up to 4 years Adverse events are reported for each arm group (i.e. Arm A, Arm B, Arm A Eligible for Crossover, and Arm B Eligible for Crossover)	0.00% 0/7 • Up to 4 years Adverse events are reported for each arm group (i.e. Arm A, Arm B, Arm A Eligible for Crossover, and Arm B Eligible for Crossover)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, mal, uncpec - Oth spec	0.00% 0/12 • Up to 4 years Adverse events are reported for each arm group (i.e. Arm A, Arm B, Arm A Eligible for Crossover, and Arm B Eligible for Crossover)	16.7% 2/12 • Number of events 2 • Up to 4 years Adverse events are reported for each arm group (i.e. Arm A, Arm B, Arm A Eligible for Crossover, and Arm B Eligible for Crossover)	0.00% 0/7 • Up to 4 years Adverse events are reported for each arm group (i.e. Arm A, Arm B, Arm A Eligible for Crossover, and Arm B Eligible for Crossover)	0.00% 0/7 • Up to 4 years Adverse events are reported for each arm group (i.e. Arm A, Arm B, Arm A Eligible for Crossover, and Arm B Eligible for Crossover)
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/12 • Up to 4 years Adverse events are reported for each arm group (i.e. Arm A, Arm B, Arm A Eligible for Crossover, and Arm B Eligible for Crossover)	0.00% 0/12 • Up to 4 years Adverse events are reported for each arm group (i.e. Arm A, Arm B, Arm A Eligible for Crossover, and Arm B Eligible for Crossover)	0.00% 0/7 • Up to 4 years Adverse events are reported for each arm group (i.e. Arm A, Arm B, Arm A Eligible for Crossover, and Arm B Eligible for Crossover)	14.3% 1/7 • Number of events 1 • Up to 4 years Adverse events are reported for each arm group (i.e. Arm A, Arm B, Arm A Eligible for Crossover, and Arm B Eligible for Crossover)
Renal and urinary disorders Acute kidney injury	0.00% 0/12 • Up to 4 years Adverse events are reported for each arm group (i.e. Arm A, Arm B, Arm A Eligible for Crossover, and Arm B Eligible for Crossover)	25.0% 3/12 • Number of events 3 • Up to 4 years Adverse events are reported for each arm group (i.e. Arm A, Arm B, Arm A Eligible for Crossover, and Arm B Eligible for Crossover)	0.00% 0/7 • Up to 4 years Adverse events are reported for each arm group (i.e. Arm A, Arm B, Arm A Eligible for Crossover, and Arm B Eligible for Crossover)	0.00% 0/7 • Up to 4 years Adverse events are reported for each arm group (i.e. Arm A, Arm B, Arm A Eligible for Crossover, and Arm B Eligible for Crossover)

Other adverse events

Additional Information

Svetomir N. Markovic MD, PhD

Mayo Clinic

Phone: 507/266-0800

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place