Overview

This trial is active, not recruiting.

Condition recurrent endometrial carcinoma
Treatments bevacizumab, temsirolimus
Phase phase 2
Targets mTOR, VEGF
Sponsor National Cancer Institute (NCI)
Start date September 2008
End date July 2011
Trial size 53 participants
Trial identifier NCT00723255, CDR0000601291, GOG-0229G, NCI-2009-00598, U10CA027469

Summary

This phase II trial is studying the side effects of giving bevacizumab together with temsirolimus and to see how well it works in treating patients with recurrent or persistent endometrial cancer. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for their growth. Giving bevacizumab together with temsirolimus may kill more tumor cells.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Patients receive bevacizumab IV on days 1 and 15 and temsirolimus IV on days 1, 8, 15, and 22.
bevacizumab anti-VEGF humanized monoclonal antibody
Given IV
temsirolimus CCI-779
Given IV

Primary Outcomes

Measure
Tumor Response
time frame: Scans are done while patient is on study therapy every other cycle for the first 6 months; then every 3 cycles thereafter; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease
Progression-free Survival at 6 Months
time frame: Every other cycle for 6 months
Frequency and Severity of Adverse Events Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0
time frame: Up to 5 years

Secondary Outcomes

Measure
Progression-Free Survival
time frame: Scans are done while patient is on study therapy every other cycle for the first 6 months; then every 3 cycles thereafter; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease.
Overall Survival
time frame: From entry into the study to death or the date of last contact, up to 5 years
Complete and Partial Tumor Response by RECIST 1.0 by Performance Status
time frame: Scans are done while patient is on study therapy every other cycle for the first 6 months; then every 3 cycles thereafter; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease
Progression-free Survival at 6 Months by Performance Status
time frame: Every other cycle for 6 months
Complete and Partial Tumor Response by RECIST 1.0 by Histologic Type
time frame: Scans are done while patient is on study therapy every other cycle for the first 6 months; then every 3 cycles thereafter; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease
Progression-free Survival at 6 Months by Histologic Type
time frame: Every other cycle for 6 months
Complete and Partial Tumor Response by RECIST 1.0 by Tumor Grade
time frame: Scans are done while patient is on study therapy every other cycle for the first 6 months; then every 3 cycles thereafter; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease
Progression-free Survival at 6 Months by Tumor Grade
time frame: Every other cycle for 6 months
The Frequency and Severity of Adverse Effects as Assessed by CTCAE v3.0
time frame: Up to 5 years

Eligibility Criteria

Female participants at least 18 years old.

Inclusion Criteria: - Histologically confirmed endometrial carcinoma (from primary tumor) including any of the following cell types: - Endometrioid adenocarcinoma - Serous adenocarcinoma - Undifferentiated carcinoma - Clear cell adenocarcinoma - Mixed epithelial carcinoma - Adenocarcinoma not otherwise specified - Mucinous adenocarcinoma - Squamous cell carcinoma - Transitional cell carcinoma - Mesonephric carcinoma - Recurrent or persistent disease that is refractory to curative therapy or established treatments - 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 to assess response as defined by RECIST - Tumors within a previously irradiated field are designated as "non-target" lesions in the absence of documented disease progression or a biopsy to confirm persistence for ≥ 90 days after completion of radiotherapy - Must have received 1 prior chemotherapeutic regimen for management of endometrial carcinoma - May have received 1 additional cytotoxic regimen for management of this disease - Not eligible for a higher priority Gynecologic Oncology Group (GOG) protocol, including any active GOG Phase III protocol for patients with endometrial carcinoma - No history or evidence of CNS disease, including primary brain tumor or any brain metastases upon physical examination - GOG performance status (PS) 0-2 (for patients who have received 1 prior regimen) OR PS 0-1 (for patients who have received 2 prior regimens) - ANC ≥ 1,500/mcL - Platelet count ≥ 100,000/mcL - Creatinine ≤ 1.5 times upper limit of normal (ULN) - Bilirubin ≤ 1.5 times ULN - SGOT ≤ 2.5 times ULN - Alkaline phosphatase ≤ 2.5 times ULN - Urine protein:creatinine ratio < 1.0 OR urine protein < 1,000 mg by 24-hour urine collection - INR ≤ 1.5 OR in-range INR between 2 and 3 if patient is on a stable dose of therapeutic warfarin - PTT ≤ 1.5 times ULN - Fasting cholesterol < 350 mg/dL - Fasting triglycerides < 400 mg/dL - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception - Seizures allowed provided they are controlled with standard medical therapy - No active infection requiring antibiotics, except uncomplicated urinary tract infection - No active bleeding or pathologic conditions that carry high risk of bleeding, (e.g., known bleeding disorder, coagulopathy, or tumor involving major vessels) - No serious, non-healing wound, ulcer, or bone fracture, including abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 3 months - No prior underlying lesions that caused the fistula or perforation that have not been corrected - No prior interstitial pneumonitis - No clinically significant cardiovascular disease, including any of the following: - Uncontrolled hypertension, defined as systolic blood pressure (BP) > 150 mm Hg or diastolic BP > 90 mm Hg - Myocardial infarction or unstable angina within the past 6 months - New York Heart Association class II-IV congestive heart failure - Serious cardiac arrhythmia requiring medication - Peripheral vascular disease ≥ grade 2 - No cerebrovascular accident, transient ischemic attack, or subarachnoid hemorrhage within the past 6 months - No uncontrolled diabetes - Hemoglobin A1C < 10 - No other invasive malignancies within the past 5 years, except nonmelanoma skin cancer and other specific malignancies (e.g., localized breast, head and neck, or skin cancer that completed treatment > 3 years prior to study and remain disease-free) - No significant traumatic injury within the past 28 days - No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies - Concurrent prophylactic or therapeutic anticoagulation* (e.g., warfarin) allowed - Recovered from recent surgery, radiotherapy, or chemotherapy - No prior bevacizumab or other VEGF pathway-targeted therapy - No prior temsirolimus, everolimus, deforolimus, sirolimus, or any other mTor/PI3K pathway-targeted therapy - No prior non-cytotoxic chemotherapy for management of this disease, except hormonal therapy - At least 1 week since prior hormonal therapy directed at the malignant tumor - No prior therapy that contraindicates this protocol therapy - No prior radiotherapy to any portion of the abdominal cavity or pelvis within the past 5 years, except treatment of endometrial cancer - Prior radiotherapy for localized cancer of the breast, head and neck, or skin is allowed, provided it was completed > 3 years prior to study entry and patient remains free of recurrent or metastatic disease - No prior chemotherapy for any abdominal or pelvic tumor within the past 5 years, except treatment of endometrial cancer - Prior adjuvant chemotherapy for localized breast cancer allowed, provided it was completed > 3 years prior to study entry and the patient remains free of recurrent or metastatic disease - Prior treatment with an anthracycline (i.e., doxorubicin and/or liposomal doxorubicin) allowed provided ejection fraction < 50% - More than 28 days since prior major surgery or open biopsy - More than 7 days since minor surgical procedures, fine needle aspirates, or core biopsies - At least 3 weeks since prior therapy directed at the malignant tumor, including immunologic agents - No concurrent major surgery - No concurrent prophylactic filgrastim (G-CSF) or thrombopoietic agents - No concurrent amifostine or other protective reagents

Additional Information

Official title A Phase II Evaluation of Combination Bevacizumab (NCI-Supplied Agent: NSC #70486) and Temsirolimus (CCI-779, NCI-Supplied Agent, NSC #683864) in the Treatment of Recurrent or Persistent Endometrial Carcinoma
Principal investigator Edwin Alvarez
Description PRIMARY OBJECTIVES: I. To assess the activity of bevacizumab and temsirolimus, in terms of 6-month progression-free survival (PFS) and objective tumor response, in patients with recurrent or persistent endometrial cancer. II. To determine the nature and degree of toxicity of this regimen in these patients. SECONDARY OBJECTIVES: I. To determine the duration of PFS and overall survival of patients treated with this regimen. II. To determine the effects of prognostic factors (i.e., performance status, histological subtype, and grade) in patients treated with this regimen. TERTIARY OBJECTIVES: I. To compare the proportion of patients with objective tumor response and PFS at 6 months receiving the combination of bevacizumab and temsirolimus with those for the single agents bevacizumab and temsirolimus using historical controls. OUTLINE: This is a multicenter study. Patients receive bevacizumab IV on days 1 and 15 and temsirolimus IV 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 therapy, patients are followed every 3 months for 2 years, then every 6 months for 3 years, for a total of 5 years.
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by National Cancer Institute (NCI).