A Phase I Study of CCI-779 (Temsirolimus) in Combination With Topotecan in Patients With Gynecologic Malignancies

Sponsor

University of Chicago (Other)

Overall Status

Completed

CT.gov ID

NCT00523432

Collaborator

Wyeth is now a wholly owned subsidiary of Pfizer (Industry)

Enrollment

Location

Arms

Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The aim of the trial is to determine the recommended phase II dose of weekly intravenous topotecan in combination with a fixed dose (25 mg or 15 mg) of weekly intravenous temsirolimus in patients with and without prior pelvic radiation.

Condition or Disease	Intervention/Treatment	Phase
Genital Neoplasms, Female	Drug: Topotecan Drug: CCI-779 (temsirolimus)	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

15 participants

Allocation:

Non-Randomized

Intervention Model:

Factorial Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Study of CCI-779 (Temsirolimus) in Combination With Topotecan in Patients With Gynecologic Malignancies

Study Start Date :

Aug 1, 2007

Actual Primary Completion Date :

Sep 1, 2009

Actual Study Completion Date :

Dec 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A Arm A will consist of subjects without prior pelvic radiation or with radiation to a field smaller than the whole pelvis. Subjects will receive weekly CCI-779 and topotecan at the assigned dose.	Drug: Topotecan Weekly doses via IV infusion. Dose will be assigned based on time of study entry. Drug: CCI-779 (temsirolimus) Weekly 25mg dose via IV infusion.
Experimental: B Arm A will consist of subjects with prior whole pelvic radiation. Subjects will receive weekly CCI-779 and topotecan at the assigned dose.	Drug: Topotecan Weekly doses via IV infusion. Dose will be assigned based on time of study entry. Drug: CCI-779 (temsirolimus) Weekly 25mg dose via IV infusion.

Arm

Intervention/Treatment

Experimental: A

Arm A will consist of subjects without prior pelvic radiation or with radiation to a field smaller than the whole pelvis. Subjects will receive weekly CCI-779 and topotecan at the assigned dose.

Drug: Topotecan

Weekly doses via IV infusion. Dose will be assigned based on time of study entry.

Drug: CCI-779 (temsirolimus)

Weekly 25mg dose via IV infusion.

Experimental: B

Arm A will consist of subjects with prior whole pelvic radiation. Subjects will receive weekly CCI-779 and topotecan at the assigned dose.

Drug: Topotecan

Weekly doses via IV infusion. Dose will be assigned based on time of study entry.

Drug: CCI-779 (temsirolimus)

Weekly 25mg dose via IV infusion.

Outcome Measures

Primary Outcome Measures

Tolerability of regimen [4 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed recurrent or metastatic ovarian carcinoma, fallopian tube carcinoma, primary peritoneal carcinoma, cervical carcinoma, endometrial carcinoma, vulvar carcinoma, vaginal carcinoma, or carcinosarcoma of the ovary, endometrium or cervix.
Prior Therapy: at least one and may have up to three prior cytotoxic chemotherapeutic regimens for the management of primary disease.
Must be at least 18 years of age.
GOG performance status must be 0 or 1.
Patients must have adequate organ and marrow function as defined below:
hemoglobin ≥10g/dL
absolute neutrophil count ≥1,500/uL
platelets ≥100,000/uL
total bilirubin below the institutional upper limit of normal
AST(SGOT)/ALT(SGPT) below the institutional upper limit of normal
creatinine below the institutional upper limit of normal
cholesterol ≤ 350 mg/dL (fasting)
triglycerides ≤ 400 mg/dL (fasting)
albumin ≥ 3.0 mg/dL
negative pregnancy test for women able to have children
Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

Prior therapy with topotecan
More than 3 prior cytotoxic chemotherapeutic regimens or treatment with temsirolimus or any other mTOR inhibitor
Concomitant hormonal therapy or radiation therapy
Clinically significant infections or other medical problems of significant severity
History of unstable angina or myocardial infarction within the past six months
Known brain metastases unless the metastases have been controlled by prior surgery or radiotherapy, and the patient has been neurologically stable and off of steroids for at least 4 weeks.
Any requirement for oxygen
Cannot be receiving potent enzyme-inducing antiepileptic drugs (EIAEDs; e.g., phenytoin, carbamazepine, phenobarbital) nor any other potent CYP3A4 inducer such as rifampin or St. John's wort, as these may decrease temsirolimus levels. Use of agents that potently inhibit CYP3A4 (and hence may raise temsirolimus levels), such as ketoconazole, is discouraged, but not specifically prohibited.