Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase I Study of CCI-779 (Temsirolimus) in Combination With Topotecan in Patients With Gynecologic Malignancies
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.


Options:
A: Inclusion Criteria:

* Histologically confirmed high grade serous and/or undifferentiated carcinoma of ovary, fallopian tube or peritoneum
* Oestrogen, progesterone and HER2 negative advanced adenocarcinoma of the breast
* Known BRCA positive breast cancer or ovarian cancer, that is not high grade serous or undifferentiated tubo-ovarian carcinoma.
* Performance status of no more than 2.

Exclusion Criteria:

* Any chemotherapy, radiotherapy ( except palliative), endocrine or immunotherapy within 4 weeks prior to entry
* Major surgery with 4 weeks of entering the study and must have recovered from effects of any major surgery .
B: 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.
C: Inclusion Criteria:

* Advanced ovarian cancer with positive BRCA1 or BRCA2 status
* Failed at least one prior chemotherapy
* In investigators opinion, no curative standard therapy exists
* Measurable disease

Exclusion Criteria:

* Brain metastases
* Less than 28 days since last treatment used to treat the disease
* Considered a poor medical risk due to a serious uncontrolled disorder
D: 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)

Answer: B