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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00408655
First received: December 6, 2006
Last updated: December 13, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
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
Stage IV Ovarian Germ Cell Tumor
Unspecified Adult Solid Tumor, Protocol Specific
Drug: paclitaxel
Drug: carboplatin
Drug: temsirolimus
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of CCI-779 (NSC 683864, IND #61010) in Combination With Carboplatin and Paclitaxel in Patients With Advanced Solid Tumours

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Recommended phase II dose of temsirolimus, carboplatin, and paclitaxel [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Safety [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Tolerability [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Dose-limiting toxicities [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Efficacy [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]

Enrollment: 30
Study Start Date: February 2007
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I

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.

Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Drug: temsirolimus
Given IV
Other Names:
  • CCI-779
  • cell cycle inhibitor 779
  • Torisel

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Criteria:

  • Histologically confirmed solid tumors
  • Measurable or nonmeasurable disease: No serum tumor marker elevation as the only evidence of disease; Patients with ovarian or endometrial cancer must have measurable disease, defined as >= 1 lesion >= 20 mm by conventional techniques OR >= 10 mm by spiral CT scan
  • Advanced disease; Refractory to standard therapy OR no standard therapy is available
  • Carboplatin and paclitaxel considered reasonable therapeutic option
  • No known brain metastases
  • ECOG performance status 0-1
  • Life expectancy >= 12 weeks
  • Absolute granulocyte count >= 1,500/mm^3
  • Platelet count >= 100,000/mm^3
  • Bilirubin =< 1.5 times upper limit of normal (ULN)
  • AST and ALT =< 3 times ULN (5 times ULN if documented liver metastases)
  • Fasting serum cholesterol =< 9.0 mmol/L
  • Fasting triglycerides =< 4.56 mmol/L
  • Creatinine normal OR creatinine clearance >= 50 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Accessible for treatment and follow up
  • No serious cardiovascular illness, including any of the following:

myocardial infarction within the past 6 months, congestive heart failure (even if medically controlled), unstable angina, active cardiomyopathy, cardiac arrhythmia, uncontrolled hypertension

  • No preexisting sensory or motor neuropathy >= grade 2 due to previous chemotherapy; Local or regional neurological findings related to previous injury or disease allowed
  • No hearing loss >= grade 2 from any cause
  • No history of allergic reactions attributed to compounds of similar chemical or biological composition to temsirolimus
  • No serious illness or medical condition that would preclude study treatment including, but not limited to, any of the following: History of significant neurologic or psychiatric disorder that would impair the ability to obtain consent or limit study compliance, Active uncontrolled infection or nonhealing wounds, OR;
  • At least 4 weeks since prior radiotherapy (except low-dose, palliative radiotherapy) and recovered
  • At least 4 weeks since prior chemotherapy and recovered
  • No more than 2 prior chemotherapy regimens
  • Prior therapy with carboplatin and/or paclitaxel allowed provided the patient has no persistent related toxicity >= grade 1 AND retreatment with the combination is clinically indicated (e.g., second-line therapy for ovarian cancer with > 6-month treatment-free interval)
  • At least 21 days since prior major surgery and recovered
  • No prior mTOR inhibitor
  • No concurrent prophylactic hematopoietic colony-stimulating factors
  • No other concurrent anticancer therapy or investigational agents
  • Active peptic ulcer disease, Any other medical condition that might be aggravated by treatment
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00408655

Locations
Canada, Ontario
National Cancer Institute of Canada Clinical Trials Group
Kingston, Ontario, Canada, K7L 3N6
Sponsors and Collaborators
Investigators
Principal Investigator: Amit Oza NCIC Clinical Trials Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00408655     History of Changes
Other Study ID Numbers: NCI-2009-00691, NCI-2009-00691, CDR0000652060, IND.179, NCIC-179
Study First Received: December 6, 2006
Last Updated: December 13, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Neoplasms, Germ Cell and Embryonal
Germinoma
Ovarian Neoplasms
Neoplasms
Endometrial Neoplasms
Neoplasms, Glandular and Epithelial
Sarcoma
Neoplasms by Histologic Type
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Uterine Neoplasms
Uterine Diseases
Neoplasms, Connective and Soft Tissue
Sirolimus
Everolimus
Carboplatin
Paclitaxel
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antifungal Agents

ClinicalTrials.gov processed this record on April 16, 2014