Temsirolimus, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Tumors

Phase 1

Completed

• Conditions: Ovarian Sarcoma; Ovarian Stromal Cancer; Recurrent Endometrial Carcinoma; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Stage III Endometrial Carcinoma; Stage III Ovarian Epithelial Cancer; Stage III Ovarian Germ Cell Tumor; Stage IV Endometrial Carcinoma; Stage IV Ovarian Epithelial Cancer
• Interventions: Drug: paclitaxel; Drug: carboplatin; Drug: temsirolimus

• Registration Number: NCT00408655
• Lead Sponsor: National Cancer Institute (NCI)

Brief Summary

This phase I trial is studying the side effects and best dose of temsirolimus, carboplatin, and paclitaxel in treating patients with advanced solid tumors. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving temsirolimus together with chemotherapy may kill more tumor cells.

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose (MTD) and recommended phase II dose of temsirolimus, carboplatin, and paclitaxel in patients with advanced solid tumors.

SECONDARY OBJECTIVES:

I. Determine the frequency and severity of toxic effects of this regimen in these patients.

II. Document any evidence of objective antitumor activity of this regimen in patients with measurable disease.

III. Determine the pharmacokinetic profile of carboplatin and paclitaxel alone, temsirolimus alone, and carboplatin, paclitaxel, and temsirolimus in combination in these patients.

OUTLINE: This is a multicenter, open-label, dose-escalation study. Patients receive treatment in either part A or part B.

PART A: Patients receive paclitaxel IV over 3 hours followed by carboplatin IV over 30-60 minutes on day 1 and temsirolimus IV over 30 minutes on days 8 and 15. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

PART B: Patients receive paclitaxel and carboplatin as in part A. They also receive temsirolimus IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients in parts A and B receive escalating doses of temsirolimus, carboplatin, and paclitaxel until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. The recommended phase II dose (RPTD) is the dose that is one dose level below the MTD. Once the RPTD is determined in part A, patients are enrolled in part B. An expanded cohort of up to 10 patients with endometrial or ovarian cancer are treated at the RPTD determined in part B (final RPTD).

After completion of study treatment, patients are followed at 4 weeks and then every 3 months thereafter.

Study Timeline

• Study First Submitted: 2006-12-06
• Study First Submitted QC: 2006-12-06
• Study First Posted: 2006-12-07
• Study Start: 2007-02
• Primary Completion: 2012-01
• Status Verified: 2014-06
• Last Update Submitted: 2014-06-18
• Last Update Posted: 2014-06-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 38

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm I	paclitaxel	PART A: Patients receive paclitaxel IV over 3 hours followed by carboplatin IV over 30-60 minutes on day 1 and temsirolimus IV over 30 minutes on days 8 and 15. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. PART B: Patients receive paclitaxel and carboplatin as in part A. They also receive temsirolimus IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.
Arm I	temsirolimus	PART A: Patients receive paclitaxel IV over 3 hours followed by carboplatin IV over 30-60 minutes on day 1 and temsirolimus IV over 30 minutes on days 8 and 15. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. PART B: Patients receive paclitaxel and carboplatin as in part A. They also receive temsirolimus IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.
Arm I	carboplatin	PART A: Patients receive paclitaxel IV over 3 hours followed by carboplatin IV over 30-60 minutes on day 1 and temsirolimus IV over 30 minutes on days 8 and 15. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. PART B: Patients receive paclitaxel and carboplatin as in part A. They also receive temsirolimus IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Recommended phase II dose of temsirolimus, carboplatin, and paclitaxel	Up to 3 years
Safety	Up to 3 years
Tolerability	Up to 3 years
Dose-limiting toxicities	Up to 3 years

Secondary Outcome Measures

Name	Time	Method
Efficacy	Up to 3 years

Trial Locations

Locations (1)

National Cancer Institute of Canada Clinical Trials Group; 🇨🇦 Kingston, Ontario, Canada