Clinical trial NCT00429793: Temsirolimus in Treating Patients With Refractory or Recurrent Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Fallopian Tube Cancer
Primary Peritoneal Cavity Cancer
Recurrent Ovarian Epithelial Cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: Gynecologic Oncology Group
First posted: 2007-02-01
Enrollment: 60
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: 6 Month Progression-free Survival (PFS)
timeFrame: 6 months
measure: Objective Tumor Response Based on the Gynecologic Oncology Group (GOG) Response Evaluation Criteria in Solid Tumors (RECIST) Criteria
timeFrame: Up to 5 years
measure: Frequency and Severity of Adverse Events as Assessed by the Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE v3.0)
timeFrame: Up to 5 years
Secondary outcomes:
measure: Duration of Progression-free Survival
timeFrame: CT scan or MRI if used to follow lesion for measurable disease every other cycle for the first 6 months up to 5 years
measure: Duration of Overall Survival
timeFrame: 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.
Other outcomes:
measure: Reason Off Study Therapy
timeFrame: from study entry until end of study treatment
measure: Patient Vital Status
timeFrame: Study entry up to 2 years
Locations:
city: Philadelphia
country: United States
facility: Gynecologic Oncology Group
state: Pennsylvania
Study officials:
affiliation: Gynecologic Oncology Group
name: Kian Behbakht
role: PRINCIPAL_INVESTIGATOR
References:
citation: Behbakht K, Sill MW, Darcy KM, Rubin SC, Mannel RS, Waggoner S, Schilder RJ, Cai KQ, Godwin AK, Alpaugh RK. Phase II trial of the mTOR inhibitor, temsirolimus and evaluation of circulating tumor cells and tumor biomarkers in persistent and recurrent epithelial ovarian and primary peritoneal malignancies: a Gynecologic Oncology Group study. Gynecol Oncol. 2011 Oct;123(1):19-26. doi: 10.1016/j.ygyno.2011.06.022. Epub 2011 Jul 12.
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.