Trial Outcomes & Findings for Pazopanib and Paclitaxel as First-Line Treatment for Subjects With Unresectable Stage III and Stage IV Melanoma (NCT NCT01107665)

Results Overview

This is defined as the percentage of subjects who are free of RECIST-defined objective disease progression at 6 months after study treatment start. Subjects in the Intent-to-Treat (ITT) population who discontinue the study prior to 6 months will be included in the denominator when calculating the percentage. Progression is defined using the Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions or appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

60 participants

Primary outcome timeframe

6 Months

Results posted on

2019-08-07

Participant Flow

Participant milestones

Participant milestones
Measure	Pazopanib and Paclitaxel Treatment on study will be administered in 4-week cycles. Paclitaxel will be administered intravenously at a starting dose of 80mg/m2 weekly for 3 weeks followed by a 1-week rest. Pazopanib will be administered orally, in a continuous regimen, with a starting dose of 800mg daily. Pazopanib and Paclitaxel: Paclitaxel will be administered intravenously at a starting dose of 80mg/m2 weekly for 3 weeks followed by a 1-week rest. Pazopanib will be administered orally, in a continuous regimen, with a starting dose of 800mg daily.
Overall Study STARTED	60
Overall Study COMPLETED	11
Overall Study NOT COMPLETED	49

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pazopanib and Paclitaxel as First-Line Treatment for Subjects With Unresectable Stage III and Stage IV Melanoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pazopanib and Paclitaxel n=60 Participants Treatment on study will be administered in 4-week cycles. Paclitaxel will be administered intravenously at a starting dose of 80mg/m2 weekly for 3 weeks followed by a 1-week rest. Pazopanib will be administered orally, in a continuous regimen, with a starting dose of 800mg daily. Pazopanib and Paclitaxel: Paclitaxel will be administered intravenously at a starting dose of 80mg/m2 weekly for 3 weeks followed by a 1-week rest. Pazopanib will be administered orally, in a continuous regimen, with a starting dose of 800mg daily.
Age, Continuous	64 years n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants
Sex: Female, Male Male	45 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	54 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants
Race (NIH/OMB) White	54 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	60 participants n=5 Participants

PRIMARY outcome

Timeframe: 6 Months

This is defined as the percentage of subjects who are free of RECIST-defined objective disease progression at 6 months after study treatment start. Subjects in the Intent-to-Treat (ITT) population who discontinue the study prior to 6 months will be included in the denominator when calculating the percentage. Progression is defined using the Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions or appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

Outcome measures

Outcome measures
Measure	Pazopanib and Paclitaxel n=60 Participants Treatment on study will be administered in 4-week cycles. Paclitaxel will be administered intravenously at a starting dose of 80mg/m2 weekly for 3 weeks followed by a 1-week rest. Pazopanib will be administered orally, in a continuous regimen, with a starting dose of 800mg daily. Pazopanib and Paclitaxel: Paclitaxel will be administered intravenously at a starting dose of 80mg/m2 weekly for 3 weeks followed by a 1-week rest. Pazopanib will be administered orally, in a continuous regimen, with a starting dose of 800mg daily.	BRAF WT/Unknown Group Subset of subjects who are BRAF WT or unknown status.
Percentage of Participants With Progression-free Survival at 6 Months	68 percentage of participants	—

SECONDARY outcome

Timeframe: At 1 year after enrollment

This is defined as the percentage of subjects who are alive at 1 year after enrollment. For subjects who do not die, time to death will be censored at the time of last contact.

Outcome measures

Outcome measures
Measure	Pazopanib and Paclitaxel n=60 Participants Treatment on study will be administered in 4-week cycles. Paclitaxel will be administered intravenously at a starting dose of 80mg/m2 weekly for 3 weeks followed by a 1-week rest. Pazopanib will be administered orally, in a continuous regimen, with a starting dose of 800mg daily. Pazopanib and Paclitaxel: Paclitaxel will be administered intravenously at a starting dose of 80mg/m2 weekly for 3 weeks followed by a 1-week rest. Pazopanib will be administered orally, in a continuous regimen, with a starting dose of 800mg daily.	BRAF WT/Unknown Group Subset of subjects who are BRAF WT or unknown status.
Percentage of Participants Alive at 1 Year	48 percentage of participants	—

SECONDARY outcome

Timeframe: At 2 years after enrollment

This is defined as the percentage of subjects who are alive at 2 years after enrollment. For subjects who do not die, time to death will be censored at the time of last contact.

Outcome measures

Outcome measures
Measure	Pazopanib and Paclitaxel n=60 Participants Treatment on study will be administered in 4-week cycles. Paclitaxel will be administered intravenously at a starting dose of 80mg/m2 weekly for 3 weeks followed by a 1-week rest. Pazopanib will be administered orally, in a continuous regimen, with a starting dose of 800mg daily. Pazopanib and Paclitaxel: Paclitaxel will be administered intravenously at a starting dose of 80mg/m2 weekly for 3 weeks followed by a 1-week rest. Pazopanib will be administered orally, in a continuous regimen, with a starting dose of 800mg daily.	BRAF WT/Unknown Group Subset of subjects who are BRAF WT or unknown status.
Percentage of Participants Alive at 2 Years	27 percentage of participants	—

SECONDARY outcome

Timeframe: Up to 2 years

This is defined as the percentage of subjects achieving either a complete or partial tumor response per RECIST criteria. The response rate will be calculated from the review of best response which records confirmed cases of PR and CR only. Confirmation will occur at least 4 weeks after the initial response. Stable disease (SD) will also be defined by 8 weeks or greater and will be summarized by less than 6 months vs. equal or greater than 6 months. Subjects in the ITT population with unknown or missing response will be treated as non-responders, i.e. they will be included in the denominator when calculating the percentage. Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0): Complete Response (CR) is defined as the disappearance of all target lesions; Partial Response (PR) is defined as a 30% decrease in the sum of the longest diameter of target lesions; Overall Reponse (ORR) = CR + PR.

Outcome measures

Outcome measures
Measure	Pazopanib and Paclitaxel n=60 Participants Treatment on study will be administered in 4-week cycles. Paclitaxel will be administered intravenously at a starting dose of 80mg/m2 weekly for 3 weeks followed by a 1-week rest. Pazopanib will be administered orally, in a continuous regimen, with a starting dose of 800mg daily. Pazopanib and Paclitaxel: Paclitaxel will be administered intravenously at a starting dose of 80mg/m2 weekly for 3 weeks followed by a 1-week rest. Pazopanib will be administered orally, in a continuous regimen, with a starting dose of 800mg daily.	BRAF WT/Unknown Group Subset of subjects who are BRAF WT or unknown status.
Objective Response Rate (ORR)	36 percentage of participants	—

SECONDARY outcome

Timeframe: Up to 2 years

This is defined as the percentage of subjects achieving either a complete (CR), partial tumor (PR) or stable disease (SD) response per RECIST criteria. Confirmation will occur at least 4 weeks after the initial response for partial and complete responders. Stable disease will also be defined by 8 weeks or greater. Subjects in the ITT population with unknown or missing response will be treated as non-responders, i.e. they will be included in the denominator when calculating the percentage. Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0): Complete Response (CR) is defined as the disappearance of all target lesions; Partial Response (PR) is defined as a 30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD or the persistence of one ore more non-target lesions; Clinical Benefit Rate = (SD+PR+CR).

Outcome measures

Outcome measures
Measure	Pazopanib and Paclitaxel n=60 Participants Treatment on study will be administered in 4-week cycles. Paclitaxel will be administered intravenously at a starting dose of 80mg/m2 weekly for 3 weeks followed by a 1-week rest. Pazopanib will be administered orally, in a continuous regimen, with a starting dose of 800mg daily. Pazopanib and Paclitaxel: Paclitaxel will be administered intravenously at a starting dose of 80mg/m2 weekly for 3 weeks followed by a 1-week rest. Pazopanib will be administered orally, in a continuous regimen, with a starting dose of 800mg daily.	BRAF WT/Unknown Group Subset of subjects who are BRAF WT or unknown status.
Clinical Benefit Response (CBR)	91 percentage of participants	—

SECONDARY outcome

Timeframe: Time from first documented evidence of response (CR/PR) until the first documented sign of disease progression or death, assessed up to 2 years

Population: Duration of response analyses will be restricted to the subgroup of the population who experience a response during the study. Duration of response will be defined as the time from first documented evidence of response (CR/PR) until the first documented sign of disease progression or death, if sooner.

Duration of response analyses will be restricted to the subgroup of the population who experience a response during the study. Duration of response will be defined as the time from first documented evidence of response (CR/PR) until the first documented sign of disease progression or death, if sooner. For subjects who do not progress or die, duration of response will be censored on the date of last assessment. Duration of response will be summarized using the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Pazopanib and Paclitaxel n=20 Participants Treatment on study will be administered in 4-week cycles. Paclitaxel will be administered intravenously at a starting dose of 80mg/m2 weekly for 3 weeks followed by a 1-week rest. Pazopanib will be administered orally, in a continuous regimen, with a starting dose of 800mg daily. Pazopanib and Paclitaxel: Paclitaxel will be administered intravenously at a starting dose of 80mg/m2 weekly for 3 weeks followed by a 1-week rest. Pazopanib will be administered orally, in a continuous regimen, with a starting dose of 800mg daily.	BRAF WT/Unknown Group Subset of subjects who are BRAF WT or unknown status.
Duration of Response (DR)	351.7 days Standard Deviation 284.9	—

SECONDARY outcome

Timeframe: From baseline until date of first documented progression, until initiation of a subsequent anti-cancer therapy, until death, whichever came first, assessed until death, the patient withdraws consent, or the study ends, up to 2 years

Population: Please refer to the Adverse Event tables for specifics.

AEs and toxicities will be graded according to the National Cancer Institute-common toxicity criteria (NCI-CTC), Version 3.0. Summaries of the number of toxicity grades for both laboratory and non-laboratory data will be presented. If the AE is listed in the NCI-CTC, the maximum grade will be summarized. Otherwise, the maximum intensity will be summarized. AEs will be coded using the standard dictionary (MedDRA), and grouped by system organ class. They will be summarized by frequency and proportion of total subjects, by system organ class and preferred term. Separate summaries will be given for all AEs, for drug-related AEs, for SAEs, and for AEs leading to withdrawal from the study treatment. The incidence of deaths will also be reported. Please refer to the Adverse Event table for specifics.

Outcome measures

Outcome measures
Measure	Pazopanib and Paclitaxel n=60 Participants Treatment on study will be administered in 4-week cycles. Paclitaxel will be administered intravenously at a starting dose of 80mg/m2 weekly for 3 weeks followed by a 1-week rest. Pazopanib will be administered orally, in a continuous regimen, with a starting dose of 800mg daily. Pazopanib and Paclitaxel: Paclitaxel will be administered intravenously at a starting dose of 80mg/m2 weekly for 3 weeks followed by a 1-week rest. Pazopanib will be administered orally, in a continuous regimen, with a starting dose of 800mg daily.	BRAF WT/Unknown Group Subset of subjects who are BRAF WT or unknown status.
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Other Safety Parameters	60 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1

Population: Exploratory endpoints were not analyzed due to depletion of funds.

Categorical statistical analysis will be performed to determine the relationship between PD and pharmacokinetic (PK) markers and outcomes. Univariate summary statistics will be calculated, such as the sample median, standard deviation, minimum, and maximum observations. The dichotomized variables were tabulated as high and low levels or positive and negative expression. Changes over time in continuously distributed biomarker levels will be investigated with the sign's test because of the heavy degree of skewness observed in some of the marginal distributions. There are no results for this exploratory endpoint due to cuts in funding.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1

Population: Exploratory endpoints were not analyzed due to depletion of funds.

Categorical statistical analysis will be performed to determine the relationship between PD and PK markers and outcomes. Univariate summary statistics will be calculated, such as the sample median, standard deviation, minimum, and maximum observations. The dichotomized variables were tabulated as high and low levels or positive and negative expression. Changes over time in continuously distributed biomarker levels will be investigated with the sign's test because of the heavy degree of skewness observed in some of the marginal distributions. There are no results for this exploratory endpoint due to cuts in funding.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1

Population: Exploratory endpoints were not analyzed due to depletion of funds.

In vitro response of tumor cells grown in culture with vascular endothelial cells to pazopanib, paclitaxel, topotecan and resveratrol. There are no results for this exploratory endpoint due to cuts in funding.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 36 months

Population: Stage III/IV melanoma

Comparison of OS between BRAF mutant subset and BRAF WT/unknown group.

Outcome measures

Outcome measures
Measure	Pazopanib and Paclitaxel n=14 Participants Treatment on study will be administered in 4-week cycles. Paclitaxel will be administered intravenously at a starting dose of 80mg/m2 weekly for 3 weeks followed by a 1-week rest. Pazopanib will be administered orally, in a continuous regimen, with a starting dose of 800mg daily. Pazopanib and Paclitaxel: Paclitaxel will be administered intravenously at a starting dose of 80mg/m2 weekly for 3 weeks followed by a 1-week rest. Pazopanib will be administered orally, in a continuous regimen, with a starting dose of 800mg daily.	BRAF WT/Unknown Group n=46 Participants Subset of subjects who are BRAF WT or unknown status.
(BRAF) Mutation Status vs Survival	18 months Interval 12.6 to 22.6	11.3 months Interval 8.0 to 13.5

Adverse Events

Pazopanib and Paclitaxel

Serious events: 10 serious events

Other events: 44 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Pazopanib and Paclitaxel n=60 participants at risk Treatment on study will be administered in 4-week cycles. Paclitaxel will be administered intravenously at a starting dose of 80mg/m2 weekly for 3 weeks followed by a 1-week rest. Pazopanib will be administered orally, in a continuous regimen, with a starting dose of 800mg daily. Pazopanib and Paclitaxel: Paclitaxel will be administered intravenously at a starting dose of 80mg/m2 weekly for 3 weeks followed by a 1-week rest. Pazopanib will be administered orally, in a continuous regimen, with a starting dose of 800mg daily.
General disorders Fatigue	13.3% 8/60 • Adverse events were collected and recorded from receipt of first receipt of first of study drug until 28 days have elapsed following cessation of study drug, regardless of initiation of a new cancer therapy or transfer to hospice. AEs were collected systematically through regular investigator assessments and laboratory testing. SAEs were either grade 3 or 4 according to the NCI Common Terminology Criteria for Adverse Events, version 3.0.
Gastrointestinal disorders Diarrhea	5.0% 3/60 • Adverse events were collected and recorded from receipt of first receipt of first of study drug until 28 days have elapsed following cessation of study drug, regardless of initiation of a new cancer therapy or transfer to hospice. AEs were collected systematically through regular investigator assessments and laboratory testing. SAEs were either grade 3 or 4 according to the NCI Common Terminology Criteria for Adverse Events, version 3.0.
Cardiac disorders Hypertension	1.7% 1/60 • Adverse events were collected and recorded from receipt of first receipt of first of study drug until 28 days have elapsed following cessation of study drug, regardless of initiation of a new cancer therapy or transfer to hospice. AEs were collected systematically through regular investigator assessments and laboratory testing. SAEs were either grade 3 or 4 according to the NCI Common Terminology Criteria for Adverse Events, version 3.0.
Blood and lymphatic system disorders Transaminitis	16.7% 10/60 • Adverse events were collected and recorded from receipt of first receipt of first of study drug until 28 days have elapsed following cessation of study drug, regardless of initiation of a new cancer therapy or transfer to hospice. AEs were collected systematically through regular investigator assessments and laboratory testing. SAEs were either grade 3 or 4 according to the NCI Common Terminology Criteria for Adverse Events, version 3.0.
Blood and lymphatic system disorders Neutropenia	15.0% 9/60 • Adverse events were collected and recorded from receipt of first receipt of first of study drug until 28 days have elapsed following cessation of study drug, regardless of initiation of a new cancer therapy or transfer to hospice. AEs were collected systematically through regular investigator assessments and laboratory testing. SAEs were either grade 3 or 4 according to the NCI Common Terminology Criteria for Adverse Events, version 3.0.
General disorders Nausea	1.7% 1/60 • Adverse events were collected and recorded from receipt of first receipt of first of study drug until 28 days have elapsed following cessation of study drug, regardless of initiation of a new cancer therapy or transfer to hospice. AEs were collected systematically through regular investigator assessments and laboratory testing. SAEs were either grade 3 or 4 according to the NCI Common Terminology Criteria for Adverse Events, version 3.0.

Other adverse events

Other adverse events
Measure	Pazopanib and Paclitaxel n=60 participants at risk Treatment on study will be administered in 4-week cycles. Paclitaxel will be administered intravenously at a starting dose of 80mg/m2 weekly for 3 weeks followed by a 1-week rest. Pazopanib will be administered orally, in a continuous regimen, with a starting dose of 800mg daily. Pazopanib and Paclitaxel: Paclitaxel will be administered intravenously at a starting dose of 80mg/m2 weekly for 3 weeks followed by a 1-week rest. Pazopanib will be administered orally, in a continuous regimen, with a starting dose of 800mg daily.
General disorders Fatigue	73.3% 44/60 • Adverse events were collected and recorded from receipt of first receipt of first of study drug until 28 days have elapsed following cessation of study drug, regardless of initiation of a new cancer therapy or transfer to hospice. AEs were collected systematically through regular investigator assessments and laboratory testing. SAEs were either grade 3 or 4 according to the NCI Common Terminology Criteria for Adverse Events, version 3.0.
Gastrointestinal disorders Diarrhea	61.7% 37/60 • Adverse events were collected and recorded from receipt of first receipt of first of study drug until 28 days have elapsed following cessation of study drug, regardless of initiation of a new cancer therapy or transfer to hospice. AEs were collected systematically through regular investigator assessments and laboratory testing. SAEs were either grade 3 or 4 according to the NCI Common Terminology Criteria for Adverse Events, version 3.0.
Cardiac disorders Hypertension	58.3% 35/60 • Adverse events were collected and recorded from receipt of first receipt of first of study drug until 28 days have elapsed following cessation of study drug, regardless of initiation of a new cancer therapy or transfer to hospice. AEs were collected systematically through regular investigator assessments and laboratory testing. SAEs were either grade 3 or 4 according to the NCI Common Terminology Criteria for Adverse Events, version 3.0.
General disorders Nausea	48.3% 29/60 • Adverse events were collected and recorded from receipt of first receipt of first of study drug until 28 days have elapsed following cessation of study drug, regardless of initiation of a new cancer therapy or transfer to hospice. AEs were collected systematically through regular investigator assessments and laboratory testing. SAEs were either grade 3 or 4 according to the NCI Common Terminology Criteria for Adverse Events, version 3.0.
Blood and lymphatic system disorders Transaminitis	35.0% 21/60 • Adverse events were collected and recorded from receipt of first receipt of first of study drug until 28 days have elapsed following cessation of study drug, regardless of initiation of a new cancer therapy or transfer to hospice. AEs were collected systematically through regular investigator assessments and laboratory testing. SAEs were either grade 3 or 4 according to the NCI Common Terminology Criteria for Adverse Events, version 3.0.
Blood and lymphatic system disorders Anemia	21.7% 13/60 • Adverse events were collected and recorded from receipt of first receipt of first of study drug until 28 days have elapsed following cessation of study drug, regardless of initiation of a new cancer therapy or transfer to hospice. AEs were collected systematically through regular investigator assessments and laboratory testing. SAEs were either grade 3 or 4 according to the NCI Common Terminology Criteria for Adverse Events, version 3.0.
Blood and lymphatic system disorders Thrombocytopenia	6.7% 4/60 • Adverse events were collected and recorded from receipt of first receipt of first of study drug until 28 days have elapsed following cessation of study drug, regardless of initiation of a new cancer therapy or transfer to hospice. AEs were collected systematically through regular investigator assessments and laboratory testing. SAEs were either grade 3 or 4 according to the NCI Common Terminology Criteria for Adverse Events, version 3.0.
Blood and lymphatic system disorders Neutropenia	30.0% 18/60 • Adverse events were collected and recorded from receipt of first receipt of first of study drug until 28 days have elapsed following cessation of study drug, regardless of initiation of a new cancer therapy or transfer to hospice. AEs were collected systematically through regular investigator assessments and laboratory testing. SAEs were either grade 3 or 4 according to the NCI Common Terminology Criteria for Adverse Events, version 3.0.

Additional Information

UC Irvine Health / Chao Family Comprehensive Cancer Center

Phone: 1-877-UC-STUDY

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place