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

NCT00523432 | Completed Phase 1

• 1 other identifier: 15424A
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Genital Neoplasms, Female

Keywords

ovarian cancer; cervical cancer; uterine cancer; fallopian tube cancer; endometrial cancer; vaginal cancer; peritoneal cancer; reproductive cancer

Outcome Measures

Primary Outcomes (1)

• Tolerability of regimen

  4 weeks

Study Arms (2)

A

EXPERIMENTAL

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; Drug: CCI-779 (temsirolimus)

B

EXPERIMENTAL

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; Drug: CCI-779 (temsirolimus)

Interventions

Topotecan DRUG

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

A; B

CCI-779 (temsirolimus) DRUG

Weekly 25mg dose via IV infusion.

A; B

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Chicago: lead
• Wyeth is now a wholly owned subsidiary of Pfizer: collaborator

Study Sites (1)

University of Chicago

Chicago, Illinois, 60637, United States

Location

Related Publications (2)

• 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.

  PMID: 20347480 RESULT

• Yap TA, Carden CP, Kaye SB. Beyond chemotherapy: targeted therapies in ovarian cancer. Nat Rev Cancer. 2009 Mar;9(3):167-81. doi: 10.1038/nrc2583.

  PMID: 19238149 DERIVED

MeSH Terms

Conditions

Genital Neoplasms, Female; Ovarian Neoplasms; Uterine Cervical Neoplasms; Uterine Neoplasms; Fallopian Tube Neoplasms; Endometrial Neoplasms; Vaginal Neoplasms

Interventions

Topotecan; temsirolimus

Condition Hierarchy (Ancestors)

Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Endocrine System Diseases; Gonadal Disorders; Uterine Cervical Diseases; Uterine Diseases; Fallopian Tube Diseases; Vaginal Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• Gini Fleming, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2007
• First Posted: August 31, 2007
• Study Start: August 1, 2007
• Primary Completion: September 1, 2009
• Study Completion: December 1, 2010
• Last Updated: September 5, 2013

Record last verified: 2013-09

Locations

US (1)