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

• ClinicalTrials.gov Identifier: NCT01407562
• Recruitment Status: Terminated
• First Posted: August 2, 2011
• Last Update Posted: September 28, 2022
• Sponsor: Rutgers, The State University of New Jersey
• Collaborators: National Cancer Institute (NCI); Rutgers Cancer Institute of New Jersey; GlaxoSmithKline
• Information provided by (Responsible Party): Nancy Chan, MD, Rutgers, The State University of New Jersey

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Unspecified Adult Solid Tumor - Protocol Specific; Breast Cancer - Female	Drug: Pazopanib; Drug: Paclitaxel; Drug: Carboplatin	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 34 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I Study of Pazopanib in Combination With Weekly Paclitaxel and Carboplatin to Assess the Safety and Tolerability in Patients With Advanced Solid Tumors
• Actual Study Start Date: September 17, 2010
• Actual Primary Completion Date: March 29, 2016
• Actual Study Completion Date: March 29, 2016

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Establish the maximum tolerated dose (MTD) of pazopanib with weekly paclitaxel and carboplatin on a 28- day cycle [ Time Frame: 4 years, 6 months ]

   Toxicity will be assessed every 28 days up to 30 days after the last dose of treatment. Dose limiting toxicity is defined as

   1. Non-hematological toxicity ≥ grade 3 (excluding alopecia, nausea, vomiting, or diarrhea for which adequate supportive therapy has not been instituted).

   2. Hematologic toxicity:

      • Grade 4 neutropenia lasting ≥ 7 days
      • Grade 4 neutropenia and fever of ≥ 38.5°C
      • ≥ Grade 3 neutropenia with ≥ Grade 3 infection
      • Grade 4 thrombocytopenia
      • Inability to start next cycle of treatment by more than 4 weeks due to unresolved toxicity

Secondary Outcome Measures :

1. Determine the drug-drug interactions with paclitaxel, carboplatin, and pazopanib [ Time Frame: 4 years, 3 months ]

   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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, New Jersey

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States, 08903

Sponsors and Collaborators

Rutgers, The State University of New Jersey

National Cancer Institute (NCI)

Rutgers Cancer Institute of New Jersey

GlaxoSmithKline

Investigators

• Principal Investigator: Nancy Chan, MD; Rutgers Cancer Institute of New Jersey

More Information

• Responsible Party: Nancy Chan, MD, Assistant Professor of Medicine, Rutgers, The State University of New Jersey
• ClinicalTrials.gov Identifier: NCT01407562
• 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 )
• First Posted: August 2, 2011
• Last Update Posted: September 28, 2022
• Last Verified: September 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Additional relevant MeSH terms:

Neoplasms; Paclitaxel; Carboplatin; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action