Study of Pazopanib, Paclitaxel, and Carboplatin in Patients With Advanced Solid Tumors

Phase I Study of Pazopanib in Combination With Weekly Paclitaxel and Carboplatin to Assess the Safety and Tolerability in Patients With Advanced Solid Tumors

This is an open label, dose escalation study to determine the safety and tolerability and maximum tolerated dose of pazopanib combined with weekly paclitaxel and carboplatin in patients with advanced solid tumors.

Study Overview

• Status: Terminated
• Conditions: Breast Cancer - Female; Unspecified Adult Solid Tumor - Protocol Specific
• Intervention / Treatment: Drug: Pazopanib; Drug: Paclitaxel; Drug: Carboplatin

Detailed Description

This is an open label, dose escalation study to determine the maximum tolerated dose (MTD) of pazopanib combined with weekly paclitaxel and carboplatin in patients with advanced solid tumors. There will be a dose expansion cohort of thirty patients to assess detailed pharmacokinetics and to assess any signal of activity in patients with solid tumors and in a portion who have breast cancer that is triple negative (ER-negative, PR-negative, and HER2-negative).

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Confirmed diagnosis of a solid malignancy with advanced disease that has relapsed, that is refractory to standard therapies, or for which there is not standard therapy, or for which the patient opts not to receive standard therapy.
• At the recommended phase II dose level, triple-negative breast cancer defined as ER-negative, PR-negative, and HER2-negative, will be enrolled and another 10 patients with a solid malignancy who would benefit from a paclitaxel and carboplatin-based regimen, will also be enrolled.
• Male or female ≥ 18 years of age
• Able to swallow and retain oral medications

Exclusion Criteria:

• Major surgery within last 28 days or cytotoxic chemotherapy, biologic therapy, investigational agents, or radiotherapy within last 21 days. Patients who have completed therapy with mitomycin C or nitrosurea will have to wait 42 days.
• More than 3 prior lines of cytotoxic chemotherapy for metastatic disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pazopanib with paclitaxel and carboplatin	Drug: Pazopanib; Starting dose is 400 given on Days 2-5, 9-12, and 16-26 of each 28 day cycle; Drug: Paclitaxel; Starting dose is 60 mg/m2 IV on days 1, 8, and 15 of each 28 day cycle; Drug: Carboplatin; Starting dose of carboplatin that corresponds to an AUC of 2, IV on days 1, 8, and 15 of each 28 day cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Establish the maximum tolerated dose (MTD) of pazopanib with weekly paclitaxel and carboplatin on a 28- day cycle	Toxicity will be assessed every 28 days up to 30 days after the last dose of treatment. Dose limiting toxicity is defined as; Non-hematological toxicity ≥ grade 3 (excluding alopecia, nausea, vomiting, or diarrhea for which adequate supportive therapy has not been instituted).; Hematologic toxicity:Grade 4 neutropenia lasting ≥ 7 daysGrade 4 neutropenia and fever of ≥ 38.5°C≥ Grade 3 neutropenia with ≥ Grade 3 infectionGrade 4 thrombocytopeniaInability to start next cycle of treatment by more than 4 weeks due to unresolved toxicity	4 years, 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine the drug-drug interactions with paclitaxel, carboplatin, and pazopanib	The first 15 patients enrolled in the dose expansion cohort will undergo PK sampling as this is felt to be an adequate sample size. 4 blood samples (2 mL each) for the analysis of paclitaxel will be obtained in Cycle 1 Day 1 and Cycle 2 Day 1 2 blood samples (2 mL each) for the analysis of carboplatin will be obtained in Cycle 1 Day 1 and Cycle 2 Day 1 1 blood sample (2 mL) for the analysis of pazopanib will be collected in Cycle 2 Day 1	4 years, 3 months

Collaborators and Investigators

• Sponsor: Rutgers, The State University of New Jersey
• Collaborators: National Cancer Institute (NCI); GlaxoSmithKline; Rutgers Cancer Institute of New Jersey
• Investigators: Principal Investigator: Nancy Chan, MD, Rutgers Cancer Institute of New Jersey

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2010
• Primary Completion (Actual): March 29, 2016
• Study Completion (Actual): March 29, 2016

Study Registration Dates

• First Submitted: July 20, 2011
• First Submitted That Met QC Criteria: July 29, 2011
• First Posted (Estimate): August 2, 2011

Study Record Updates

• Last Update Posted (Actual): September 28, 2022
• Last Update Submitted That Met QC Criteria: September 26, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Carboplatin; Paclitaxel
• Other Study ID Numbers: Pro0220110062; P30CA072720 (U.S. NIH Grant/Contract); NCI-2011-02448 (Other Identifier: CTRP (Clinical Trails Reporting Program)); 051101 (Other Identifier: Rutgers Cancer Institute of New Jersey)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO