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

National Cancer Institute (NCI)

Status and phase

Completed

Phase 2

Conditions

Recurrent Endometrial Carcinoma

Treatments

Biological: bevacizumab

Drug: temsirolimus

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00723255

U10CA027469 (U.S. NIH Grant/Contract)

CDR0000601291

NCI-2009-00598 (Registry Identifier)

GOG-0229G (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

53 patients

Sex

Female

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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