Clinical trial NCT00723255: Bevacizumab and Temsirolimus in Treating Patients With Recurrent or Persistent Endometrial Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Recurrent Endometrial Carcinoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: NRG Oncology
First posted: 2008-07-28
Enrollment: 53
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Tumor Response
timeFrame: 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
measure: Progression-free Survival at 6 Months
timeFrame: Every other cycle for 6 months
measure: Frequency and Severity of Adverse Events Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0
timeFrame: Every cycle and 30 days after the last treatment, an average of 5 years.
Secondary outcomes:
measure: Progression-Free Survival
timeFrame: 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.
measure: Overall Survival
timeFrame: From entry into the study to death or the date of last contact, up to 5 years
measure: Complete and Partial Tumor Response by RECIST 1.0 by Performance Status
timeFrame: 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
measure: Progression-free Survival at 6 Months by Performance Status
timeFrame: Every other cycle for 6 months
measure: Complete and Partial Tumor Response by RECIST 1.0 by Histologic Type
timeFrame: 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
measure: Progression-free Survival at 6 Months by Histologic Type
timeFrame: Every other cycle for 6 months
measure: Complete and Partial Tumor Response by RECIST 1.0 by Tumor Grade
timeFrame: 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
measure: Progression-free Survival at 6 Months by Tumor Grade
timeFrame: Every other cycle for 6 months
Other outcomes:
Locations:
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: New Britain
country: United States
facility: The Hospital of Central Connecticut
state: Connecticut
city: Washington
country: United States
facility: Washington Hospital Center
state: District of Columbia
city: Savannah
country: United States
facility: Memorial University Medical Center
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Hinsdale
country: United States
facility: Sudarshan K Sharma MD Limted-Gynecologic Oncology
state: Illinois
city: Elkhart
country: United States
facility: Elkhart General Hospital
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University Medical Center
state: Indiana
city: Indianapolis
country: United States
facility: Saint Vincent Hospital and Health Services
state: Indiana
city: Kokomo
country: United States
facility: Community Howard Regional Health
state: Indiana
city: La Porte
country: United States
facility: IU Health La Porte Hospital
state: Indiana
city: Mishawaka
country: United States
facility: Saint Joseph Regional Medical Center-Mishawaka
state: Indiana
city: South Bend
country: United States
facility: Memorial Hospital of South Bend
state: Indiana
city: South Bend
country: United States
facility: South Bend Clinic
state: Indiana
city: South Bend
country: United States
facility: Northern Indiana Cancer Research Consortium
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Grand Rapids
country: United States
facility: Gynecologic Oncology of West Michigan PLLC
state: Michigan
city: Saint Joseph
country: United States
facility: Lakeland Hospital
state: Michigan
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Independence
country: United States
facility: Centerpoint Medical Center LLC
state: Missouri
city: Kansas City
country: United States
facility: Truman Medical Center
state: Missouri
city: Saint Louis
country: United States
facility: Saint Louis University Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Springfield
country: United States
facility: Mercy Hospital Springfield
state: Missouri
city: Springfield
country: United States
facility: Ozark Health Ventures LLC-Cancer Research for The Ozarks Springfield
state: Missouri
city: Camden
country: United States
facility: Cooper Hospital University Medical Center
state: New Jersey
city: Albany
country: United States
facility: Women's Cancer Care Associates LLC
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Greenville
country: United States
facility: Gynecologic Oncology Network
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Cleveland
country: United States
facility: MetroHealth Medical Center
state: Ohio
city: Columbus
country: United States
facility: Riverside Methodist Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Tulsa
country: United States
facility: Tulsa Cancer Institute
state: Oklahoma
city: Abington
country: United States
facility: Abington Memorial Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Providence
country: United States
facility: Women and Infants Hospital
state: Rhode Island
city: Anderson
country: United States
facility: AnMed Health Cancer Center
state: South Carolina
city: Roanoke
country: United States
facility: Carilion Clinic Gynecological Oncology
state: Virginia
Study officials:
affiliation: Gynecologic Oncology Group
name: Edwin Alvarez
role: PRINCIPAL_INVESTIGATOR
References: