A Phase I Study of CCI-779 (Temsirolimus) in Combination With Topotecan in Patients With Gynecologic Malignancies
Primary Purpose
Genital Neoplasms, Female
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Topotecan
CCI-779 (temsirolimus)
Sponsored by
About this trial
This is an interventional treatment trial for Genital Neoplasms, Female focused on measuring ovarian cancer, cervical cancer, uterine cancer, fallopian tube cancer, endometrial cancer, vaginal cancer, peritoneal cancer, reproductive cancer
Eligibility Criteria
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.
Sites / Locations
- University of Chicago
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
A
B
Arm Description
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.
Arm A will consist of subjects with prior whole pelvic radiation. Subjects will receive weekly CCI-779 and topotecan at the assigned dose.
Outcomes
Primary Outcome Measures
Tolerability of regimen
Secondary Outcome Measures
Full Information
NCT ID
NCT00523432
First Posted
August 29, 2007
Last Updated
September 4, 2013
Sponsor
University of Chicago
Collaborators
Wyeth is now a wholly owned subsidiary of Pfizer
1. Study Identification
Unique Protocol Identification Number
NCT00523432
Brief Title
A Phase I Study of CCI-779 (Temsirolimus) in Combination With Topotecan in Patients With Gynecologic Malignancies
Official Title
A Phase I Study of CCI-779 (Temsirolimus) in Combination With Topotecan in Patients With Gynecologic Malignancies
Study Type
Interventional
2. Study Status
Record Verification Date
September 2013
Overall Recruitment Status
Completed
Study Start Date
August 2007 (undefined)
Primary Completion Date
September 2009 (Actual)
Study Completion Date
December 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Chicago
Collaborators
Wyeth is now a wholly owned subsidiary of Pfizer
4. Oversight
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Genital Neoplasms, Female
Keywords
ovarian cancer, cervical cancer, uterine cancer, fallopian tube cancer, endometrial cancer, vaginal cancer, peritoneal cancer, reproductive cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Factorial Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
15 (Actual)
8. Arms, Groups, and Interventions
Arm Title
A
Arm Type
Experimental
Arm Description
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.
Arm Title
B
Arm Type
Experimental
Arm Description
Arm A will consist of subjects with prior whole pelvic radiation. Subjects will receive weekly CCI-779 and topotecan at the assigned dose.
Intervention Type
Drug
Intervention Name(s)
Topotecan
Intervention Description
Weekly doses via IV infusion. Dose will be assigned based on time of study entry.
Intervention Type
Drug
Intervention Name(s)
CCI-779 (temsirolimus)
Intervention Description
Weekly 25mg dose via IV infusion.
Primary Outcome Measure Information:
Title
Tolerability of regimen
Time Frame
4 weeks
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gini Fleming, MD
Organizational Affiliation
University of Chicago
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
20347480
Citation
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.
Results Reference
result
PubMed Identifier
19238149
Citation
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.
Results Reference
derived
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A Phase I Study of CCI-779 (Temsirolimus) in Combination With Topotecan in Patients With Gynecologic Malignancies
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