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

Recurrent Endometrial Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00723255
• Other study ID #: NCI-2009-00598
• Secondary ID: NCI-2009-00598CD
• Status: Completed
• Phase: Phase 2
• Start date: September 2008
• Est. completion date: January 25, 2016

Study information

• Verified date: July 2019
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: January 25, 2016
• Est. primary completion date: July 15, 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Endometrial Neoplasms
• Recurrent Endometrial Carcinoma

Intervention

Biological:
• bevacizumab
Given IV

Drug:
• temsirolimus
Given IV

Locations

Country	Name	City	State
United States	Abington Memorial Hospital	Abington	Pennsylvania
United States	Women's Cancer Care Associates LLC	Albany	New York
United States	AnMed Health Cancer Center	Anderson	South Carolina
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Carolinas Medical Center	Charlotte	North Carolina
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Gynecologic Oncology of West Michigan PLLC	Grand Rapids	Michigan
United States	Gynecologic Oncology Network	Greenville	North Carolina
United States	Hartford Hospital	Hartford	Connecticut
United States	Sudarshan K Sharma MD Limted-Gynecologic Oncology	Hinsdale	Illinois
United States	Centerpoint Medical Center LLC	Independence	Missouri
United States	Indiana University Medical Center	Indianapolis	Indiana
United States	Saint Vincent Hospital and Health Services	Indianapolis	Indiana
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Truman Medical Center	Kansas City	Missouri
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	The Hospital of Central Connecticut	New Britain	Connecticut
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Women and Infants Hospital	Providence	Rhode Island
United States	Carilion Clinic Gynecological Oncology	Roanoke	Virginia
United States	Lakeland Hospital	Saint Joseph	Michigan
United States	Saint Louis University Hospital	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Memorial University Medical Center	Savannah	Georgia
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Northern Indiana Cancer Research Consortium	South Bend	Indiana
United States	South Bend Clinic	South Bend	Indiana
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Ozark Health Ventures LLC-Cancer Research for The Ozarks Springfield	Springfield	Missouri
United States	Tulsa Cancer Institute	Tulsa	Oklahoma
United States	Washington Hospital Center	Washington	District of Columbia
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	NRG Oncology

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tumor Response	Complete and Partial Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) 1.0	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
Primary	Progression-free Survival at 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.	Every other cycle for 6 months
Primary	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	Progression-Free Survival	Progression-Free Survival is the period from study entry until disease progression, death or date of last contact.	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.
Secondary	Overall Survival	The observed length of life from entry into the study to death or the date of last contact.	From entry into the study to death or the date of last contact, up to 5 years
Secondary	Complete and Partial Tumor Response by RECIST 1.0 by Performance Status	Complete and Partial Tumor Response by RECIST 1.0	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
Secondary	Progression-free Survival at 6 Months by Performance Status	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.	Every other cycle for 6 months
Secondary	Complete and Partial Tumor Response by RECIST 1.0 by Histologic Type	Complete and Partial Tumor Response by RECIST 1.0	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
Secondary	Progression-free Survival at 6 Months by Histologic Type	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.	Every other cycle for 6 months
Secondary	Complete and Partial Tumor Response by RECIST 1.0 by Tumor Grade	Complete and Partial Tumor Response by RECIST 1.0	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
Secondary	Progression-free Survival at 6 Months by Tumor Grade	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.	Every other cycle for 6 months