Trial Outcomes & Findings for Phase 2 Study With Abraxane (Nab®Paclitaxel) in Metastatic Colorectal Cancer (NCT NCT02103062)

Last Updated: 2020-04-21

Results Overview

PFS rate was measured by Investigator Assessment according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 from the start of study treatment to disease progression or death from any cause, whichever occurred first.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

41 participants

Primary outcome timeframe

At week 8 assessment period; up to 56 days

Results posted on

2020-04-21

Participant Flow

Participants must have been previously treated and must have had radiologically documented measurable disease, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and disease progression ≤ 2 months after the last delivery of the last standard therapy. They were enrolled by family of oncogenic proteins (RAS) mutation status .

An efficacy analysis was conducted based on the data available for those accrued in each of the cohorts enrolled (Stage 1) between May-September 2014. The data from the primary efficacy endpoint met the stopping criteria defined by the Simon 2-stage design, which did not support further assessment of nab-paclitaxel; the study was stopped early.

Participant milestones

Participant milestones
Measure	RAS Wildtype: Nab®-Paclitaxel nab®-paclitaxel 125 mg/m\^2 on days 1, 8 and 15 of every 28 day cycle until disease progression, unacceptable toxicity, or withdrawal of consent.	RAS Mutated: Nab®-Paclitaxel nab®-paclitaxel 125 mg/m\^2 on days 1, 8 and 15 of every 28 day cycle until disease progression, unacceptable toxicity, or withdrawal of consent.
Overall Study STARTED	18	23
Overall Study Safety Population	18	23
Overall Study Intent to Treat Population	17	20
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	18	23

Reasons for withdrawal

Reasons for withdrawal
Measure	RAS Wildtype: Nab®-Paclitaxel nab®-paclitaxel 125 mg/m\^2 on days 1, 8 and 15 of every 28 day cycle until disease progression, unacceptable toxicity, or withdrawal of consent.	RAS Mutated: Nab®-Paclitaxel nab®-paclitaxel 125 mg/m\^2 on days 1, 8 and 15 of every 28 day cycle until disease progression, unacceptable toxicity, or withdrawal of consent.
Overall Study Adverse Event	1	2
Overall Study Progressive Disease	17	20
Overall Study Death	0	1

Baseline Characteristics

Phase 2 Study With Abraxane (Nab®Paclitaxel) in Metastatic Colorectal Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	RAS Wildtype: Nab®-Paclitaxel n=17 Participants nab®-paclitaxel 125 mg/m\^2 on days 1, 8 and 15 of every 28 day cycle until disease progression, unacceptable toxicity, or withdrawal of consent.	RAS Mutated: Nab®-Paclitaxel n=20 Participants nab®-paclitaxel 125 mg/m\^2 on days 1, 8 and 15 of every 28 day cycle until disease progression, unacceptable toxicity, or withdrawal of consent.	Total n=37 Participants Total of all reporting groups
Age, Continuous	64.3 years STANDARD_DEVIATION 12.34 • n=99 Participants	61.9 years STANDARD_DEVIATION 10.56 • n=107 Participants	63.0 years STANDARD_DEVIATION 11.31 • n=206 Participants
Sex: Female, Male Female	5 Participants n=99 Participants	10 Participants n=107 Participants	15 Participants n=206 Participants
Sex: Female, Male Male	12 Participants n=99 Participants	10 Participants n=107 Participants	22 Participants n=206 Participants

PRIMARY outcome

Timeframe: At week 8 assessment period; up to 56 days

Population: Per the Simon 2-stage design, only 30 participants from Stage 1 (the first 15 participants in the Intent to Treat (ITT) population from each cohort) were included. The ITT population was defined as those who received treatment and met all eligibility criteria; four ineligible participants were excluded based on the protocol deviations/violations

Outcome measures

Outcome measures
Measure	RAS Wildtype: Nab®-Paclitaxel n=15 Participants nab®-paclitaxel 125 mg/m\^2 on days 1, 8 and 15 of every 28 day cycle until disease progression, unacceptable toxicity, or withdrawal of consent.	RAS Mutated: Nab®-Paclitaxel n=15 Participants nab®-paclitaxel 125 mg/m\^2 on days 1, 8 and 15 of every 28 day cycle until disease progression, unacceptable toxicity, or withdrawal of consent.
Progression Free Survival (PFS) Rate as Measured at Week 8	20 percentage of participants Interval 4.0 to 48.0	20 percentage of participants Interval 4.0 to 48.0

SECONDARY outcome

Timeframe: At week 8 and later; up to day 241

Population: ITT Population defined as participants who received treatment and met all eligibility criteria

DCR was defined as the combined incidence of stable disease confirmed CR or PR and stable disease (SD) measured at the Week 8 assessment or later.

Outcome measures

Outcome measures
Measure	RAS Wildtype: Nab®-Paclitaxel n=17 Participants nab®-paclitaxel 125 mg/m\^2 on days 1, 8 and 15 of every 28 day cycle until disease progression, unacceptable toxicity, or withdrawal of consent.	RAS Mutated: Nab®-Paclitaxel n=20 Participants nab®-paclitaxel 125 mg/m\^2 on days 1, 8 and 15 of every 28 day cycle until disease progression, unacceptable toxicity, or withdrawal of consent.
Percentage of Participants With Stable Disease for ≥ 8 Weeks, or Complete or Partial Response According to RECIST Version 1.1; Disease Control Rate (DCR)	18 Percentage of participants Interval 4.0 to 43.0	15 Percentage of participants Interval 3.0 to 38.0

SECONDARY outcome

Timeframe: Up to 241 days

Population: The data from the primary efficacy endpoint met the stopping criteria defined by the Simon 2-stage design, which did not support further assessment of nab-paclitaxel as a monotherapy in the analysis of this group of participants. The study was stopped early and the analysis of overall survival was not performed.

Overall Survival was the time from the first dose of study drug to patient death from any cause.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 241 days

Population: ITT population defined as participants who received treatment and met all eligibility criteria.

ORR was defined as the combined incidence of Complete Response (CR) and Partial Response (PR), confirmed no less than 4 weeks after the criteria for response were first met based on RECIST 1.1. Tumor responses were assessed every 2 cycles using RECIST 1.1 and defined as: • Complete response-disappearance of all target lesions • Partial response- At least a 30% decrease in the sum of diameters of target lesions from baseline • Stable disease-neither sufficient shrinkage to qualify for PR nor sufficient increase of lesions to qualify for Progressive disease (PD) • Progressive Disease- At least a 20% increase in the sum of diameters of target lesions from nadir.

Outcome measures

Outcome measures
Measure	RAS Wildtype: Nab®-Paclitaxel n=17 Participants nab®-paclitaxel 125 mg/m\^2 on days 1, 8 and 15 of every 28 day cycle until disease progression, unacceptable toxicity, or withdrawal of consent.	RAS Mutated: Nab®-Paclitaxel n=20 Participants nab®-paclitaxel 125 mg/m\^2 on days 1, 8 and 15 of every 28 day cycle until disease progression, unacceptable toxicity, or withdrawal of consent.
Overall Response Rate (ORR)	0 percentage of participants NA because no participants experienced a CR or PR so the overall response rate in this study was zero.	0 percentage of participants NA because no participants experienced a CR or PR so the overall response rate in this study was zero.

SECONDARY outcome

Timeframe: Up to 241 days

Population: The data from the primary efficacy endpoint met the stopping criteria defined by the Simon 2-stage design, which did not support further assessment of nab-paclitaxel as a monotherapy in the analysis of this group of participants. Duration of response was not analyzed as there were no responders observed in the study.

Duration of response was defined as the time from the first tumor assessment when the confirmed CR/PR response criterion was met to the date of disease progression based on investigational assessment following RECIST 1.1.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Time of the first dose of study treatment to 28 days after the last dose of study drug; maximum treatment duration was 24 weeks

Population: Safety population includes all participants who received at least one dose of study treatment

A treatment emergent adverse events (TEAE) was defined as any AE occurring or worsening on or after the first dose of study drug and within 28 days after the last dose of study drug. A TESAE is defined as any serious adverse event (SAE) occurring or worsening on or after the first dose of study drug and within 28 days after the last dose of study drug. Safety and Severity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0; Severity of AEs were graded (including second primary malignancies) as Grade 1- Mild; Grade 2- Moderate; Grade 3- Severe; Grade 4- Lifethreatening; Grade 5-Fatal;

Outcome measures

Outcome measures
Measure	RAS Wildtype: Nab®-Paclitaxel n=18 Participants nab®-paclitaxel 125 mg/m\^2 on days 1, 8 and 15 of every 28 day cycle until disease progression, unacceptable toxicity, or withdrawal of consent.	RAS Mutated: Nab®-Paclitaxel n=23 Participants nab®-paclitaxel 125 mg/m\^2 on days 1, 8 and 15 of every 28 day cycle until disease progression, unacceptable toxicity, or withdrawal of consent.
Number of Participants With Adverse Events ≥1 or more related TEAE	17 participants	21 participants
Number of Participants With Adverse Events ≥1 TEAE with Grade 3-4	12 participants	18 participants
Number of Participants With Adverse Events ≥1 treatment related TEAE with Grade 3 or 4	9 participants	12 participants
Number of Participants With Adverse Events ≥1 or TEAE Grade 3 or higher	12 participants	18 participants
Number of Participants With Adverse Events ≥1 treatment related TEAE with Grade 3 or higher	9 participants	12 participants
Number of Participants With Adverse Events Any Serious TEAE	5 participants	10 participants
Number of Participants With Adverse Events ≥1 or more related serious TEAE	2 participants	0 participants
Number of Participants With Adverse Events ≥1TEAE with Action of Study Drug Withdrawn	1 participants	2 participants
Number of Participants With Adverse Events ≥1 treatment related TEAE Where Study Drug Reduced	6 participants	4 participants
Number of Participants With Adverse Events ≥1TEAE with study dose Interrupted	7 participants	8 participants
Number of Participants With Adverse Events ≥1 treatment related TEAE w Study Drug Interrupted	6 participants	6 participants
Number of Participants With Adverse Events ≥1TEAE with outcome of death	0 participants	1 participants
Number of Participants With Adverse Events Any TEAE	18 participants	23 participants
Number of Participants With Adverse Events ≥1treatment related TEAE WhereStudy Drug Withdrawn	1 participants	0 participants
Number of Participants With Adverse Events ≥1TEAE with Action of Study Drug Reduced	7 participants	4 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 241 days

Population: Intent-to-treat Population defined as participants who received treatment and met all eligibility criteria

PFS was measured as time from the date of first dose to the date of disease progression according to RECIST 1.1 or death from any cause, whichever was earlier.

Outcome measures

Outcome measures
Measure	RAS Wildtype: Nab®-Paclitaxel n=17 Participants nab®-paclitaxel 125 mg/m\^2 on days 1, 8 and 15 of every 28 day cycle until disease progression, unacceptable toxicity, or withdrawal of consent.	RAS Mutated: Nab®-Paclitaxel n=20 Participants nab®-paclitaxel 125 mg/m\^2 on days 1, 8 and 15 of every 28 day cycle until disease progression, unacceptable toxicity, or withdrawal of consent.
Kaplan Meier Estimate of PFS by Investigator Assessment	8.1 weeks Interval 7.71 to 8.57	7.9 weeks Interval 7.57 to 8.0

Adverse Events

RAS Wildtype: Nab®-Paclitaxel

Serious events: 5 serious events

Other events: 18 other events

Deaths: 0 deaths

RAS Mutated: Nab®-Paclitaxel

Serious events: 10 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Anne McClain, Senior Manager, Clinical Trial Disclosure

Celgene Corporation

Phone: 888-260-1599

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The investigator shall have the right to publish and/or present study data provided that the investigator shall (i) furnish the sponsor a copy of any proposed publication or presentation generally sixty (60) days in advance of the submission, (ii) delete any confidential information of the sponsor, and (iii) delay submission for generally up to ninety (90) days to permit the preparation and filing of intellectual property applications or until sponsor gives its consent in a timely manner.
Publication restrictions are in place

Restriction type: OTHER

Measure	RAS Wildtype: Nab®-Paclitaxel n=18 participants at risk nab®-paclitaxel 125 mg/m\^2 on days 1, 8 and 15 of every 28 day cycle until disease progression, unacceptable toxicity, or withdrawal of consent.	RAS Mutated: Nab®-Paclitaxel n=23 participants at risk nab®-paclitaxel 125 mg/m\^2 on days 1, 8 and 15 of every 28 day cycle until disease progression, unacceptable toxicity, or withdrawal of consent.
Blood and lymphatic system disorders Neutropenia	5.6% 1/18 • All adverse events were recorded and monitored by the investigator from the time the informed consent was signed to 28 days after the last dose of study treatment or the End of Treatment, whichever was later; maximum treatment duration was 24 weeks	0.00% 0/23 • All adverse events were recorded and monitored by the investigator from the time the informed consent was signed to 28 days after the last dose of study treatment or the End of Treatment, whichever was later; maximum treatment duration was 24 weeks
Cardiac disorders Cardio-respiratory arrest	5.6% 1/18 • All adverse events were recorded and monitored by the investigator from the time the informed consent was signed to 28 days after the last dose of study treatment or the End of Treatment, whichever was later; maximum treatment duration was 24 weeks	0.00% 0/23 • All adverse events were recorded and monitored by the investigator from the time the informed consent was signed to 28 days after the last dose of study treatment or the End of Treatment, whichever was later; maximum treatment duration was 24 weeks
Gastrointestinal disorders Abdominal pain	5.6% 1/18 • All adverse events were recorded and monitored by the investigator from the time the informed consent was signed to 28 days after the last dose of study treatment or the End of Treatment, whichever was later; maximum treatment duration was 24 weeks	0.00% 0/23 • All adverse events were recorded and monitored by the investigator from the time the informed consent was signed to 28 days after the last dose of study treatment or the End of Treatment, whichever was later; maximum treatment duration was 24 weeks
Gastrointestinal disorders Ileus	0.00% 0/18 • All adverse events were recorded and monitored by the investigator from the time the informed consent was signed to 28 days after the last dose of study treatment or the End of Treatment, whichever was later; maximum treatment duration was 24 weeks	4.3% 1/23 • All adverse events were recorded and monitored by the investigator from the time the informed consent was signed to 28 days after the last dose of study treatment or the End of Treatment, whichever was later; maximum treatment duration was 24 weeks
Gastrointestinal disorders Intestinal obstruction	0.00% 0/18 • All adverse events were recorded and monitored by the investigator from the time the informed consent was signed to 28 days after the last dose of study treatment or the End of Treatment, whichever was later; maximum treatment duration was 24 weeks	4.3% 1/23 • All adverse events were recorded and monitored by the investigator from the time the informed consent was signed to 28 days after the last dose of study treatment or the End of Treatment, whichever was later; maximum treatment duration was 24 weeks
Gastrointestinal disorders Vomiting	0.00% 0/18 • All adverse events were recorded and monitored by the investigator from the time the informed consent was signed to 28 days after the last dose of study treatment or the End of Treatment, whichever was later; maximum treatment duration was 24 weeks	4.3% 1/23 • All adverse events were recorded and monitored by the investigator from the time the informed consent was signed to 28 days after the last dose of study treatment or the End of Treatment, whichever was later; maximum treatment duration was 24 weeks
General disorders Catheter site haematoma	0.00% 0/18 • All adverse events were recorded and monitored by the investigator from the time the informed consent was signed to 28 days after the last dose of study treatment or the End of Treatment, whichever was later; maximum treatment duration was 24 weeks	4.3% 1/23 • All adverse events were recorded and monitored by the investigator from the time the informed consent was signed to 28 days after the last dose of study treatment or the End of Treatment, whichever was later; maximum treatment duration was 24 weeks
General disorders Death	0.00% 0/18 • All adverse events were recorded and monitored by the investigator from the time the informed consent was signed to 28 days after the last dose of study treatment or the End of Treatment, whichever was later; maximum treatment duration was 24 weeks	4.3% 1/23 • All adverse events were recorded and monitored by the investigator from the time the informed consent was signed to 28 days after the last dose of study treatment or the End of Treatment, whichever was later; maximum treatment duration was 24 weeks
General disorders General physical health deterioration	0.00% 0/18 • All adverse events were recorded and monitored by the investigator from the time the informed consent was signed to 28 days after the last dose of study treatment or the End of Treatment, whichever was later; maximum treatment duration was 24 weeks	13.0% 3/23 • All adverse events were recorded and monitored by the investigator from the time the informed consent was signed to 28 days after the last dose of study treatment or the End of Treatment, whichever was later; maximum treatment duration was 24 weeks
General disorders Pyrexia	0.00% 0/18 • All adverse events were recorded and monitored by the investigator from the time the informed consent was signed to 28 days after the last dose of study treatment or the End of Treatment, whichever was later; maximum treatment duration was 24 weeks	8.7% 2/23 • All adverse events were recorded and monitored by the investigator from the time the informed consent was signed to 28 days after the last dose of study treatment or the End of Treatment, whichever was later; maximum treatment duration was 24 weeks
Hepatobiliary disorders Biliary dilatation	0.00% 0/18 • All adverse events were recorded and monitored by the investigator from the time the informed consent was signed to 28 days after the last dose of study treatment or the End of Treatment, whichever was later; maximum treatment duration was 24 weeks	4.3% 1/23 • All adverse events were recorded and monitored by the investigator from the time the informed consent was signed to 28 days after the last dose of study treatment or the End of Treatment, whichever was later; maximum treatment duration was 24 weeks
Infections and infestations Abdominal abscess	5.6% 1/18 • All adverse events were recorded and monitored by the investigator from the time the informed consent was signed to 28 days after the last dose of study treatment or the End of Treatment, whichever was later; maximum treatment duration was 24 weeks	0.00% 0/23 • All adverse events were recorded and monitored by the investigator from the time the informed consent was signed to 28 days after the last dose of study treatment or the End of Treatment, whichever was later; maximum treatment duration was 24 weeks
Infections and infestations Sepsis	11.1% 2/18 • All adverse events were recorded and monitored by the investigator from the time the informed consent was signed to 28 days after the last dose of study treatment or the End of Treatment, whichever was later; maximum treatment duration was 24 weeks	0.00% 0/23 • All adverse events were recorded and monitored by the investigator from the time the informed consent was signed to 28 days after the last dose of study treatment or the End of Treatment, whichever was later; maximum treatment duration was 24 weeks
Nervous system disorders Peripheral motor neuropathy	5.6% 1/18 • All adverse events were recorded and monitored by the investigator from the time the informed consent was signed to 28 days after the last dose of study treatment or the End of Treatment, whichever was later; maximum treatment duration was 24 weeks	0.00% 0/23 • All adverse events were recorded and monitored by the investigator from the time the informed consent was signed to 28 days after the last dose of study treatment or the End of Treatment, whichever was later; maximum treatment duration was 24 weeks
Nervous system disorders Peripheral sensory neuropathy	5.6% 1/18 • All adverse events were recorded and monitored by the investigator from the time the informed consent was signed to 28 days after the last dose of study treatment or the End of Treatment, whichever was later; maximum treatment duration was 24 weeks	0.00% 0/23 • All adverse events were recorded and monitored by the investigator from the time the informed consent was signed to 28 days after the last dose of study treatment or the End of Treatment, whichever was later; maximum treatment duration was 24 weeks
Renal and urinary disorders Renal failure	0.00% 0/18 • All adverse events were recorded and monitored by the investigator from the time the informed consent was signed to 28 days after the last dose of study treatment or the End of Treatment, whichever was later; maximum treatment duration was 24 weeks	4.3% 1/23 • All adverse events were recorded and monitored by the investigator from the time the informed consent was signed to 28 days after the last dose of study treatment or the End of Treatment, whichever was later; maximum treatment duration was 24 weeks
Renal and urinary disorders Urinary tract obstruction	0.00% 0/18 • All adverse events were recorded and monitored by the investigator from the time the informed consent was signed to 28 days after the last dose of study treatment or the End of Treatment, whichever was later; maximum treatment duration was 24 weeks	4.3% 1/23 • All adverse events were recorded and monitored by the investigator from the time the informed consent was signed to 28 days after the last dose of study treatment or the End of Treatment, whichever was later; maximum treatment duration was 24 weeks
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/18 • All adverse events were recorded and monitored by the investigator from the time the informed consent was signed to 28 days after the last dose of study treatment or the End of Treatment, whichever was later; maximum treatment duration was 24 weeks	4.3% 1/23 • All adverse events were recorded and monitored by the investigator from the time the informed consent was signed to 28 days after the last dose of study treatment or the End of Treatment, whichever was later; maximum treatment duration was 24 weeks
Vascular disorders Hypotension	5.6% 1/18 • All adverse events were recorded and monitored by the investigator from the time the informed consent was signed to 28 days after the last dose of study treatment or the End of Treatment, whichever was later; maximum treatment duration was 24 weeks	0.00% 0/23 • All adverse events were recorded and monitored by the investigator from the time the informed consent was signed to 28 days after the last dose of study treatment or the End of Treatment, whichever was later; maximum treatment duration was 24 weeks