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

Genital Neoplasms, Female Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00523432
• Other study ID #: 15424A
• Status: Completed
• Phase: Phase 1
• First received: August 29, 2007
• Last updated: September 4, 2013
• Start date: August 2007
• Est. completion date: December 2010

Study information

• Verified date: September 2013
• Source: University of Chicago
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: December 2010
• Est. primary completion date: September 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Genital Neoplasms, Female

Intervention

Drug:
• Topotecan
Weekly doses via IV infusion. Dose will be assigned based on time of study entry.
• CCI-779 (temsirolimus)
Weekly 25mg dose via IV infusion.

Locations

Country	Name	City	State
United States	University of Chicago	Chicago	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
University of Chicago	Wyeth is now a wholly owned subsidiary of Pfizer

Country where clinical trial is conducted

United States, 

References & Publications (1)

Temkin SM, Yamada SD, Fleming GF. A phase I study of weekly temsirolimus and topotecan in the treatment of advanced and/or recurrent gynecologic malignancies. Gynecol Oncol. 2010 Jun;117(3):473-6. doi: 10.1016/j.ygyno.2010.02.022. Epub 2010 Mar 28. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tolerability of regimen		4 weeks	Yes