Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

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.

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

John Fruehauf, MD, PhD

This is a Phase II single-arm, open-label, clinical trial evaluating the efficacy and safety of pazopanib in combination with paclitaxel as first line therapy for subjects with unresectable Stage III and Stage IV melanoma. Previous cytokine therapy is permitted. Subjects must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST). Subjects who are not candidates for curative intent treatments are eligible for this study.

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.

Approximately 60 eligible subjects will be enrolled over a 24 month period. 21 subjects will be entered into the first stage of a 2-stage Simon Minimax design. If there are 3 or more responses, 39 additional subjects will be enrolled in Stage 2. The minimum number of responses required to move to the second stage, \> 3, were noted after the first 9 patients on treatment, and the study then proceeded towards the goal of accruing 60 total patients. Subjects are permitted to receive supportive care throughout the study including transfusion of blood and blood products, treatment with antibiotics, anti-emetics, anti-diarrheal agents, analgesics, erythropoietin, filgrastim (Neupogen), or bisphosphonates, when appropriate. Subjects should continue treatment on study until objective disease progression is documented according to RECIST or withdrawal from the study for other reasons. Subjects discontinuing treatment with paclitaxel prior to disease progression should continue treatment with pazopanib. Subjects discontinuing both agents prior to progressive disease (PD) will be followed for tumor assessment until PD, or until the initiation of a subsequent anti-cancer therapy in the absence of documented PD, or until death, whichever occurs first. Subjects may continue treatment beyond the time of RECIST-defined progression at the discretion of the investigator if the subject is perceived to be experiencing clinical benefit. Overall survival will be assessed for 2 years from first study treatment.

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

A Phase II, Single-Arm Study of Pazopanib and Paclitaxel as First-Line Treatment for Subjects With Unresectable Stage III and Stage IV Melanoma

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.

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.

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.

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

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.

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.

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.

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.

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).

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.

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.

GlaxoSmithKline

University of California, Irvine

Professor of Clinical Medicine

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.

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

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Analysis on one secondary outcome and other exploratory outcomes were not performed due to depleted funding.

UC Irvine Health / Chao Family Comprehensive Cancer Center

Percentage of Participants With Progression-free Survival at 6 Months

Percentage of Participants Alive at 1 Year

Percentage of Participants Alive at 2 Years

Objective Response Rate (ORR)

Clinical Benefit Response (CBR)

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 (DR)

Please refer to the Adverse Event tables for specifics.

Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Other Safety Parameters

Exploratory endpoints were not analyzed due to depletion of funds.

Concentrations of Plasma Proteins (Serum VEGF, Soluble VEGF Receptor 2, Serum Hypoxia-inducible Factor (HIF) and Serum TSP1) That May be Associated to Angiogenesis and Tumor Proliferation

Tissue Levels of Angiogenic Markers Including Protein (p)53, HIF, Cluster of Differentiation (CD)31, Neuronal Nitric Oxide Synthase (nNOS), TSP1, and VEGF

In Vitro Response of Tumor Cells Grown in Culture With Vascular Endothelial Cells to Pazopanib, Paclitaxel, Topotecan and Resveratrol

Subset of subjects who are BRAF mutant positive

BRAF Mutant Subset

Subset of subjects who are BRAF WT or unknown status.

BRAF WT/Unknown Group

(BRAF) Mutation Status vs Survival

Overall Study

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Ovarian Cancer

Ovarian Epithelial Cancer

Pazopanib 800mg od for 7 days, followed by 18 weeks of combination therapy (paclitaxel 80mg/m2 weekly and pazopanib 800mg od). Following the completion of combination therapy, patients will continue on maintenance pazopanib 800mg od until disease progression.

Pazopanib and paclitaxel

Rohini Sharma, MD

Timothy Crook, MD

The purpose of this study is to assess \[18F\] -fluciclatide as a biomarker of response to pazopanib and to evaluate the efficacy and safety of the combination of pazopanib and paclitaxel in platinum-resistant ovarian cancer patients.

[18F]Fluciclatide-PET, Pazopanib and Paclitaxel in Ovarian Cancer

Phase 1b Exploratory Study of [18F]Fluciclatide-PET as a Marker of Angiogenic Response to Combination Therapy With the Pan-VEGF Inhibitor, Pazopanib, and Weekly Paclitaxel in Platinum Resistant Ovarian Cancer

Semi-quantitative standardized uptake value and fully quantitative net irreversible plasma to tumour transfer constant

Core study assessments including physical examination, vital signs, ECG, and adverse event reporting

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Pazopanib and Paclitaxel as First-Line Treatment for Subjects With Unresectable Stage III and Stage IV Melanoma	NCT01107665	Stage III Melan... Stage IV Melano... Unresectable Me...	Pazopanib and P...	18 Years -	University of California, Irvine
[18F]Fluciclatide-PET, Pazopanib and Paclitaxel in Ovarian Cancer	NCT01608009	Ovarian Neoplas...	Pazopanib and p...	18 Years -	Imperial College London

Spots Global Cancer Trial Database for pazopanib and paclitaxel