Temsirolimus in Treating Patients With Refractory or Recurrent Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer

Study Overview
=================
Brief Summary
-----------------
This phase II trial is studying the side effects and how well temsirolimus works in treating patients with refractory or recurrent ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Description
-----------------
OBJECTIVES: Primary I. Determine the 6-month progression-free survival (PFS) or objective tumor response in patients with refractory or recurrent ovarian epithelial, fallopian tube, or primary peritoneal cavity cancer treated with temsirolimus. II. Determine the toxicity of this drug in these patients. Secondary I. Determine the duration of PFS and overall survival of these patients. OUTLINE: This is a nonrandomized, multicenter study. Patients receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 3 years. PROJECTED ACCRUAL: A total of 52 patients will be accrued for this study.

Official Title
-----------------
A Phase II Evaluation of CCI-779 (Temsirolimus, NCI-Supplied Agent, NSC #683864, IND #61010) in the Treatment of Persistent or Recurrent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma

Conditions
-----------------
Fallopian Tube Cancer, Primary Peritoneal Cavity Cancer, Recurrent Ovarian Epithelial Cancer

Intervention / Treatment
-----------------
* Drug: temsirolimus


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically confirmed ovarian epithelial, fallopian tube or primary peritoneal cavity cancer Recurrent or refractory Prior treatment with ≥ 1 platinum-based chemotherapeutic regimen for management of primary disease (containing carboplatin, cisplatin, or another organoplatinum compound) required Initial treatment may have included any of the following: High-dose therapy Intraperitoneal therapy Consolidation therapy Noncytotoxic agents Extended therapy administered after surgical or nonsurgical assessment Patients must meet ≥ 1 of the following criteria: Treatment-free interval after platinum therapy of < 12 months for patients who received only 1 platinum-based regimen Progressed during platinum-based therapy Refractory disease after a platinum-based regimen Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan Must have ≥ 1 target lesion Tumors within a previously irradiated field will be designated as non-target lesions unless progression is documented or a biopsy is obtained ≥ 90 days after completion of radiotherapy Not eligible for a higher priority GOG protocol, if one exists GOG performance status (PS) 0-2 for patients who have receive one prior regimen OR GOG PS 0-1 for patients who have received 2-3 prior regimens Absolute neutrophil count ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Creatinine ≤ 1.5 times upper limit normal (ULN) Bilirubin ≤ 1.5 times ULN AST ≤ 2.5 times ULN Alkaline phosphatase ≤ 2.5 times ULN No neuropathy (sensory and motor) > grade 2 Fasting cholesterol < 350 mg/dL Fasting triglycerides < 400 mg/dL Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No active infection requiring antibiotics (with the exception of uncomplicated UTI) No other invasive malignancies within the past 5 years, except for non-melanoma skin cancer, breast cancer, or head and neck cancer See Disease Characteristics Recovered from prior surgery, radiotherapy, or chemotherapy At least 1 week since prior hormonal therapy directed at the malignant tumor At least 3 years since prior radiotherapy for localized cancer of the breast, head and neck, or skin Patient must remain free of recurrent or metastatic disease At least 3 years since prior adjuvant chemotherapy for localized breast cancer Patient must remain free of recurrent or metastatic disease At least 3 weeks since other prior therapy directed at the malignant tumor, including immunologic agents No prior temsirolimus No prior cancer treatment that would preclude study therapy No prior radiotherapy to > 25% of marrow-bearing areas No prior radiotherapy to any portion of the abdominal cavity or pelvis, except for the treatment of ovarian cancer No prior non-cytotoxic therapy for management of recurrent or persistent ovarian disease, except for therapy that was part of the primary treatment regimen Two additional cytotoxic regimens (defined as any agent that targets the genetic and/or mitotic apparatus of dividing cells, resulting in dose-limiting toxicity to the bone marrow and/or gastrointestinal mucosa) for management of recurrent or persistent ovarian disease allowed Concurrent low molecular weight heparin allowed provided PT/INR ≤ 1.5 Concurrent hormone replacement therapy allowed No concurrent amifostine or other protective reagents No concurrent prophylactic filgrastim (G-CSF)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (temsirolimus)<br>Patients receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Drug: temsirolimus<br>* Given IV<br>* Other names: Torisel;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6 Month Progression-free Survival (PFS) | Number of participants who survived progression-free for more than 6 months. | 6 months | 
| Objective Tumor Response Based on the Gynecologic Oncology Group (GOG) Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Number of participants who experienced an objective tumor response up to 5 years. Per RECIST version 1.0 criteria: each target lesion must be >= 20 mm when measured by conventional techniques, including palpation, plain x-ray, CT, and MRI, or >= 10 mm when measured by spiral CT. Complete Response is a disappearance of all target and non-target lesions. Partial Response is at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable lesions, taking as reference the baseline sum of LD. Increasing Disease is at least a 20% increase in the sum of LD of target lesions, taking as references the smallest sum LD or the appearance of new lesions. | Up to 5 years | 
| Frequency and Severity of Adverse Events as Assessed by the Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE v3.0) |  | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Progression-free Survival | Progression is defined according to RECIST v1.0 as at least a 20% increase in the sum of LD target lesions taking as reference the smallest sum LD recorded since study entry, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression, or unequivocal progression of existing non-target lesions. | CT scan or MRI if used to follow lesion for measurable disease every other cycle for the first 6 months up to 5 years | 
| Duration of Overall Survival | Overall survival is defined as the duration of time from study entry to time of death or the date of last contact. | Every cycle during treatment, then every 3 months for the first 2 years, then every six months for the next three years and then annually for the next 5 years. |