Bevacizumab and Temsirolimus in Treating Patients With Recurrent or Persistent Endometrial Cancer

NCT ID: NCT00723255

Last Updated: 2019-07-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 53 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-09-30
• Study Completion Date: 2016-01-25

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.

Conditions

Recurrent Endometrial Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (bevacizumab, temsirolimus)

Patients receive bevacizumab IV on days 1 and 15 and temsirolimus IV on days 1, 8, 15, and 22.

Group Type: EXPERIMENTAL

bevacizumab

Intervention Type: BIOLOGICAL

Given IV

temsirolimus

Intervention Type: DRUG

Given IV

Interventions

bevacizumab

Given IV

Intervention Type: BIOLOGICAL

temsirolimus

Given IV

Intervention Type: DRUG

Other Intervention Names

anti-VEGF humanized monoclonal antibody; anti-VEGF monoclonal antibody; Avastin; rhuMAb VEGF; CCI-779; cell cycle inhibitor 779; Torisel

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

NRG Oncology

OTHER

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Edwin Alvarez

Role: PRINCIPAL_INVESTIGATOR

Gynecologic Oncology Group

Locations

Hartford Hospital

Hartford, Connecticut, United States

The Hospital of Central Connecticut

New Britain, Connecticut, United States

Washington Hospital Center

Washington D.C., District of Columbia, United States

Memorial University Medical Center

Savannah, Georgia, United States

Rush University Medical Center

Chicago, Illinois, United States

University of Chicago

Chicago, Illinois, United States

Sudarshan K Sharma MD Limted-Gynecologic Oncology

Hinsdale, Illinois, United States

Elkhart General Hospital

Elkhart, Indiana, United States

Indiana University Medical Center

Indianapolis, Indiana, United States

Saint Vincent Hospital and Health Services

Indianapolis, Indiana, United States

Community Howard Regional Health

Kokomo, Indiana, United States

IU Health La Porte Hospital

La Porte, Indiana, United States

Saint Joseph Regional Medical Center-Mishawaka

Mishawaka, Indiana, United States

Memorial Hospital of South Bend

South Bend, Indiana, United States

South Bend Clinic

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

Gynecologic Oncology of West Michigan PLLC

Grand Rapids, Michigan, United States

Lakeland Hospital

Saint Joseph, Michigan, United States

University of Mississippi Medical Center

Jackson, Mississippi, United States

Centerpoint Medical Center LLC

Independence, Missouri, United States

Truman Medical Center

Kansas City, Missouri, United States

Mercy Hospital Springfield

Springfield, Missouri, United States

Ozark Health Ventures LLC-Cancer Research for The Ozarks Springfield

Springfield, Missouri, United States

Saint Louis University Hospital

St Louis, Missouri, United States

Washington University School of Medicine

St Louis, Missouri, United States

Cooper Hospital University Medical Center

Camden, New Jersey, United States

Women's Cancer Care Associates LLC

Albany, New York, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Carolinas Medical Center

Charlotte, North Carolina, United States

Gynecologic Oncology Network

Greenville, North Carolina, United States

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

MetroHealth Medical Center

Cleveland, Ohio, United States

Riverside Methodist Hospital

Columbus, Ohio, United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Tulsa Cancer Institute

Tulsa, Oklahoma, United States

Abington Memorial Hospital

Abington, Pennsylvania, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Women and Infants Hospital

Providence, Rhode Island, United States

AnMed Health Cancer Center

Anderson, South Carolina, United States

Carilion Clinic Gynecological Oncology

Roanoke, Virginia, United States

Countries

United States

Other Identifiers

NCI-2009-00598

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000601291

Identifier Type: -

Identifier Source: secondary_id

GOG-0229G

Identifier Type: OTHER

Identifier Source: secondary_id

GOG-0229G

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA027469

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00598

Identifier Type: -

Identifier Source: org_study_id