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A Phase II Evaluation of Combination Bevacizumab (NCI-Supplied Agent: NSC #704865, IND #7921) and Temsirolimus (CCI-779, NCI-Supplied Agent, NSC #683864, IND #61010) in the Treatment of Recurrent or Persistent Endometrial Carcinoma

Phase 2
18 Years
Open (Enrolling)
Recurrent Endometrial Carcinoma

Thank you

Trial Information

A Phase II Evaluation of Combination Bevacizumab (NCI-Supplied Agent: NSC #704865, IND #7921) and Temsirolimus (CCI-779, NCI-Supplied Agent, NSC #683864, IND #61010) in the Treatment of Recurrent or Persistent Endometrial Carcinoma


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.


I. To determine the duration of PFS and overall survival of patients treated with this

II. To determine the effects of prognostic factors (i.e., performance status, histological
subtype, and grade) in patients treated with this regimen.


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

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.

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

- 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

- 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

- 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

- 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

- 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

- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Proportion of patients who survive progression-free

Outcome Time Frame:

At 6 months

Safety Issue:


Principal Investigator

Edwin Alvarez

Investigator Role:

Principal Investigator

Investigator Affiliation:

Gynecologic Oncology Group


United States: Food and Drug Administration

Study ID:




Start Date:

September 2008

Completion Date:

Related Keywords:

  • Recurrent Endometrial Carcinoma
  • Carcinoma
  • Adenoma
  • Endometrial Neoplasms



Memorial Sloan Kettering Cancer Center New York, New York  10021
University of Iowa Hospitals and Clinics Iowa City, Iowa  52242
University of Mississippi Medical Center Jackson, Mississippi  39216-4505
Washington University School of Medicine Saint Louis, Missouri  63110
Abington Memorial Hospital Abington, Pennsylvania  19001
Fox Chase Cancer Center Philadelphia, Pennsylvania  19111
Memorial Hospital of South Bend South Bend, Indiana  46601
Rush University Medical Center Chicago, Illinois  60612-3824
Gynecologic Oncology Network Greenville, North Carolina  27858
Hartford Hospital Hartford, Connecticut  06102-5037
Carolinas Medical Center Charlotte, North Carolina  28232-2861
University of Oklahoma Health Sciences Center Oklahoma City, Oklahoma  73104
MetroHealth Medical Center Cleveland, Ohio  44109
Elkhart General Hospital Elkhart, Indiana  46515
South Bend Clinic South Bend, Indiana  46617
AnMed Health Cancer Center Anderson, South Carolina  29621
Washington Hospital Center Washington, District of Columbia  20010
Independence Regional Health Center Independence, Missouri  64050
Saint Louis University Hospital St. Louis, Missouri  63110-0250
Riverside Methodist Hospital Columbus, Ohio  43214
Indiana University Medical Center Indianapolis, Indiana  46202
Memorial Health University Medical Center Savannah, Georgia  31404
University of Chicago Comprehensive Cancer Center Chicago, Illinois  60637-1470
Northern Indiana Cancer Research Consortium South Bend, Indiana  
Wake Forest University Health Sciences Winston-Salem, North Carolina  27157
The Hospital of Central Connecticut New Britain, Connecticut  06050
Saint Vincent Hospital and Health Services Indianapolis, Indiana  46260
Lakeland Hospital St. Joseph, Michigan  49085
Truman Medical Center Kansas City, Missouri  64108
Ozark Health Ventures LLC dba Cancer Research for The Ozarks Springfield Springfield, Missouri  65802
Saint John's Hospital Springfield, Missouri  65804
Cooper Hospital University Medical Center Camden, New Jersey  08103
Cancer Care Associates-Yale Tulsa, Oklahoma  74136-1929
Women and Infants Hospital Providence, Rhode Island  02905
Gynecologic Oncology of West Michigan PLLC Grand Rapids, Michigan  49546
Carilion Clinic Gynecological Oncology Roanoke, Virginia  24016
Community Howard Regional Health Kokomo, Indiana  46904
Indiana University Health La Porte Hospital La Porte, Indiana  46350
Saint Joseph Regional Medical Center-Mishawaka Mishawaka, Indiana  46545-1470
Women's Cancer Care Associates LLC Albany, New York  12208