A PHASE II EVALUATION OF TEMSIROLIMUS (CCI-779) (NCI SUPPLIED AGENT:NSC# 683864, IND# 61010) IN COMBINATION WITH CARBOPLATIN AND PACLITAXEL FOLLOWED BY TEMSIROLIMUS (CCI-779) CONSOLIDATION AS FIRST-LINE THERAPY IN THE TREATMENT OF STAGE III-IV CLEAR CELL CARCINOMA OF THE OVARY
- Conditions
- Stage III or IV clear cell ovarian cancer
- Registration Number
- JPRN-jRCT2091220076
- Lead Sponsor
- Gynecologic Oncology Group
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 45
1)Patients must have Stage III or IV clear cell ovarian cancer. Primary tumors must be at least 50% clear cell histomorphology in order to be eligible. In addition, the tumors should be negative for expression of WT-1 antigen and Estrogen Receptor (ER) antigen by immunohistochemistry.
2)Patients must have signed an approved informed consent and authorization permitting release of personal health information.
3)Patients with a GOG Performance Status of 0, 1, or 2.
4)Patients must be entered between 2 and 12 weeks after initial surgery performed for the combined purpose of diagnosis, staging and cytoreduction.
5)Patients must be > 18 years of age.
6)Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated UTI).
7)Patients must have adequate organ and marrow function as defined below:
Absolute neutrophil count >=1,500/mcl.
Platelets >=100,000/mcl.
Total bilirubin within normal institutional limits.
AST (SGOT) and alkaline phosphatase <=2.5 times institutional upper limit of normal (< 5 times ULN for subjects with liver metastases).
Creatinine <= 1.5 x institutional upper limit of normal, grade 1 per CTCAE v. 4.0.
Cholesterol <= 350 mg/dL (fasting) and Triglycerides <= 400 mg/dL (fasting).
Albumin >= 3.0 mg/dL.
Blood coagulation parameters: PT such that international normalized ratio (INR) is <= 1.5 (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin for management of venous thrombosis including pulmonary thrombo-embolus) and a PTT < 1.2 times the upper limit of normal.
8)Neurologic function (sensory and motor) <= CTCAE grade 1.
1)Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer, are excluded if there is any evidence of other malignancy being present within the last five years. Patients are also excluded if their previous cancer treatment contraindicates this protocol therapy.
2)Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis are excluded. Prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than five years prior to registration, and the patient remains free of recurrent or metastatic disease.
3)Patients who have received prior chemotherapy for any abdominal or pelvic tumor including neo-adjuvant chemotherapy for their clear cell ovarian cancer.
4)Patients with primary peritoneal and fallopian tube carcinoma are not eligible.
5)Previous treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus), paclitaxel, or carboplatin.
6)Patients receiving any CYP3A4 inducer.
7)Patients receiving any investigational agents.
8)Patients with severely impaired lung function defined as a diffusion lung capacity for carbon monoxide (DLCO) <= 50% of the normal predicted value and/or O2 saturation <= 88% at rest on room air.
9)Patients with symptomatic congestive heart failure of New York Heart Association Class III or IV (See Appendix III), unstable angina pectoris,symptomatic congestive heart failure, myocardial infarction <= 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant disease.
10)Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels.
11)Because of the theoretical risk of immunosuppression from mTOR inhibitors, patients on maintenance corticosteroids are ineligible with the exception of short term use (fewer than 5 days).
12)Patients with baseline requirement for oxygen.
13)Patients with serious concomitant illness which, in the opinion of the treating physician, will place patient at unreasonable risk from therapy on this protocol.
14)Patients who are pregnant or nursing. Patients of childbearing potential must agree to use contraceptive measures during study therapy and for at least six months after completion of study therapies.
15)Patients with poorly controlled diabetes.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Progression-free survival
- Secondary Outcome Measures
Name Time Method 1)Frequency and severity of adverse events<br>2)Duration of progression-free survival and overall survival<br>3)The proportion of patients who have objective tumor response(complete or partial)