Bevacizumab and Temsirolimus in Treating Patients With Recurrent or Persistent Endometrial Cancer
- Conditions
- Recurrent Endometrial Carcinoma
- Interventions
- Biological: bevacizumab
- Registration Number
- NCT00723255
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief 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.
- Detailed 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 53
-
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
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment (bevacizumab, temsirolimus) bevacizumab Patients receive bevacizumab IV on days 1 and 15 and temsirolimus IV on days 1, 8, 15, and 22. Treatment (bevacizumab, temsirolimus) temsirolimus Patients receive bevacizumab IV on days 1 and 15 and temsirolimus IV on days 1, 8, 15, and 22.
- Primary Outcome Measures
Name Time Method Progression-free Survival at 6 Months Every other cycle for 6 months Percentage of patients who are progression-free 6 months after study entry. Progression-Free Survival is the period from study entry until disease progression, death or date of last contact.
Tumor Response 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 Complete and Partial Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) 1.0
Frequency and Severity of Adverse Events Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 Every cycle and 30 days after the last treatment, an average of 5 years.
- Secondary Outcome Measures
Name Time Method Complete and Partial Tumor Response by RECIST 1.0 by Tumor Grade 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 Complete and Partial Tumor Response by RECIST 1.0
Overall Survival From entry into the study to death or the date of last contact, up to 5 years The observed length of life from entry into the study to death or the date of last contact.
Progression-free Survival at 6 Months by Performance Status Every other cycle for 6 months Percentage of patients who are progression-free 6 months after study entry. Progression-Free Survival is the period from study entry until disease progression, death or date of last contact.
Complete and Partial Tumor Response by RECIST 1.0 by Histologic Type 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 Complete and Partial Tumor Response by RECIST 1.0
Progression-free Survival at 6 Months by Tumor Grade Every other cycle for 6 months Percentage of patients who are progression-free 6 months after study entry. Progression-Free Survival is the period from study entry until disease progression, death or date of last contact.
Progression-Free Survival 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 is the period from study entry until disease progression, death or date of last contact.
Complete and Partial Tumor Response by RECIST 1.0 by Performance Status 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 Complete and Partial Tumor Response by RECIST 1.0
Progression-free Survival at 6 Months by Histologic Type Every other cycle for 6 months Percentage of patients who are progression-free 6 months after study entry. Progression-Free Survival is the period from study entry until disease progression, death or date of last contact.
Trial Locations
- Locations (41)
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
MetroHealth Medical Center
🇺🇸Cleveland, Ohio, United States
Indiana University Medical Center
🇺🇸Indianapolis, Indiana, United States
Saint Vincent Hospital and Health Services
🇺🇸Indianapolis, Indiana, United States
Mercy Hospital Springfield
🇺🇸Springfield, Missouri, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
Cooper Hospital University Medical Center
🇺🇸Camden, New Jersey, United States
Women's Cancer Care Associates LLC
🇺🇸Albany, New York, United States
Riverside Methodist Hospital
🇺🇸Columbus, Ohio, United States
Memorial University Medical Center
🇺🇸Savannah, Georgia, United States
Lakeland Hospital
🇺🇸Saint Joseph, Michigan, United States
Gynecologic Oncology Network
🇺🇸Greenville, North Carolina, United States
Truman Medical Center
🇺🇸Kansas City, Missouri, United States
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
Centerpoint Medical Center LLC
🇺🇸Independence, Missouri, United States
Ozark Health Ventures LLC-Cancer Research for The Ozarks Springfield
🇺🇸Springfield, Missouri, United States
Women and Infants Hospital
🇺🇸Providence, Rhode Island, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Tulsa Cancer Institute
🇺🇸Tulsa, Oklahoma, United States
Saint Louis University Hospital
🇺🇸Saint Louis, Missouri, United States
Hartford Hospital
🇺🇸Hartford, Connecticut, United States
Washington Hospital Center
🇺🇸Washington, District of Columbia, United States
The Hospital of Central Connecticut
🇺🇸New Britain, Connecticut, United States
Elkhart General Hospital
🇺🇸Elkhart, Indiana, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Sudarshan K Sharma MD Limted-Gynecologic Oncology
🇺🇸Hinsdale, Illinois, United States
IU Health La Porte Hospital
🇺🇸La Porte, Indiana, United States
Community Howard Regional Health
🇺🇸Kokomo, Indiana, United States
Saint Joseph Regional Medical Center-Mishawaka
🇺🇸Mishawaka, Indiana, United States
Memorial Hospital of South Bend
🇺🇸South Bend, Indiana, United States
Northern Indiana Cancer Research Consortium
🇺🇸South Bend, Indiana, United States
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
Abington Memorial Hospital
🇺🇸Abington, Pennsylvania, United States
Carilion Clinic Gynecological Oncology
🇺🇸Roanoke, Virginia, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Carolinas Medical Center
🇺🇸Charlotte, North Carolina, United States
Gynecologic Oncology of West Michigan PLLC
🇺🇸Grand Rapids, Michigan, United States
AnMed Health Cancer Center
🇺🇸Anderson, South Carolina, United States
South Bend Clinic
🇺🇸South Bend, Indiana, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States