A Phase 2 Trial of Temsirolimus and Bevacizumab in Patients With Endometrial, Ovarian, Hepatocellular Carcinoma, Carcinoid or Islet Cell Cancer
Overview
- Phase
- Phase 2
- Intervention
- Bevacizumab
- Conditions
- Adult Hepatocellular Carcinoma
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 252
- Locations
- 61
- Primary Endpoint
- Progression Free Survival Rate
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
This phase II trial studies how well temsirolimus and bevacizumab work in treating patients with advanced endometrial, ovarian, liver, carcinoid, or islet cell cancer. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 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. Bevacizumab may also stop the growth of cancer by blocking blood flow to the tumor. Giving temsirolimus together with bevacizumab may kill more tumor cells.
Detailed Description
PRIMARY OBJECTIVES: I. To determine the response rate and progression-free survival at 6 months in patients with endometrial, ovarian, hepatocellular carcinoma, carcinoid or islet cell cancer. II. To determine the toxicity of the combination of temsirolimus and bevacizumab in patients with endometrial, ovarian, hepatocellular carcinoma, carcinoid or islet cell cancer. SECONDARY OBJECTIVES: I. To collect blood and tumor specimens from all patients entered on the trial for possible future analysis. OUTLINE: Patients receive temsirolimus intravenously (IV) on days 1, 8, 15, and 22, and bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 3 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically confirmed endometrial (endometrioid, uterine, papillary serous carcinoma, and carcinosarcoma), ovarian (primary peritoneal/fallopian tube, serous, endometrioid, mixed, and poorly differentiated epithelial ovarian cancers \[for purposes of eligibility, carcinosarcoma is considered a poorly differentiated carcinoma\]), hepatocellular carcinoma, carcinoid or islet cell (neuroendocrine: well- or moderately-differentiated neuroendocrine) cancer which are locally advanced, recurrent, or metastatic
- •Patients must have measurable disease; patients having only lesions measuring \>= 1 cm to \< 2 cm must use spiral computed tomography (CT) imaging for both pre- and post-treatment tumor assessments; patients who have had prior palliative radiotherapy to metastatic lesion(s) must have at least one measurable lesion(s) that have not been previously irradiated
- •Radiation therapy (adjuvant or palliative) must be completed \>= 4 weeks prior to registration, if applicable
- •Absolute neutrophil count (ANC) \>= 1500/mm\^3
- •Platelets \>= 75,000/mm\^3
- •Hemoglobin \>= 9.0 g/dL
- •Total bilirubin =\< 1.5 x upper limit of normal (ULN); Note: direct bilirubin and international normalized ratio (INR) for hepatocellular carcinoma (HCC) patients allowed as per Child-Turcotte-Pugh scoring
- •Alkaline phosphatase =\< 2.5 x ULN (=\< 5 x ULN if liver metastasis is present or patient is in HCC cohort)
- •Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) =\< 2.5 x ULN (=\< 5 x ULN if liver metastasis is present or patient is in HCC cohort)
- •Creatinine =\<1.5 x ULN
Exclusion Criteria
- •Prior therapy with vascular endothelial growth factor receptor (VEGFR) targeting agents or mammalian target of rapamycin (mTOR) inhibitors (except as in HCC and in the Islet cell single agent bevacizumab alone cohort where prior mTOR inhibitor is allowed); Note: prior use of bevacizumab is not allowed in any cohort
- •Invasive procedures defined as follows:
- •Major surgical procedure, open biopsy or significant traumatic injury =\< 4 weeks prior to registration
- •Anticipation of need for major surgical procedures during the course of the study
- •Core biopsy =\< 7 days prior to registration
- •Serious or non-healing wound, ulcer or bone fracture
- •History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess =\< 180 days prior to first date of bevacizumab therapy
- •Evidence of bleeding diathesis or coagulopathy in the absence of therapeutic anticoagulation
- •Evidence of a history bleeding =\< 6 months such as hemoptysis, or cerebrovascular accident =\< previous 6 months, or peripheral vascular disease with claudication on \< 1 block, or history of clinically significant bleeding, because of the potential bleeding and/or clotting risk with bevacizumab
- •Untreated central nervous system (CNS) metastases; exceptions: patients with known CNS metastases can be enrolled if the brain metastases have been adequately treated and there is no evidence of progression or hemorrhage after treatment as ascertained by clinical examination and brain imaging (MRI or CT) =\< 12 weeks prior to registration and no ongoing requirement for steroids
Arms & Interventions
Treatment (temsirolimus, bevacizumab)
Patients receive temsirolimus IV on days 1, 8, 15, and 22, and bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention: Bevacizumab
Treatment (temsirolimus, bevacizumab)
Patients receive temsirolimus IV on days 1, 8, 15, and 22, and bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention: Temsirolimus
Outcomes
Primary Outcomes
Progression Free Survival Rate
Time Frame: 6 months
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. The 6-month progression free survival rate is the proportion of evaluable patients progression-free 6 months from registration. The 6-month progression-free rate is defined as the total number of efficacy evaluable patients on study without documentation of disease progression 6 months from registration divided by the total number of evaluable patients enrolled on study. Kaplan-Meier methodology will be used to estimate the final success proportion (i.e. progression free at 6 months with a 95% confidence interval).
Tumor Response Rate
Time Frame: Up to 3 years
Tumor response rate defined as the total number of efficacy-evaluable patients who achieved a complete or partial response according to the RECIST criteria divided by the total number of efficacy evaluable patients enrolled on study. Patients were evaluated using the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. In brief, a Complete Response (CR) means the complete disappearance of all target lesions and a reduction in each lymph node to \<1 cm. A Partial Response (PR) is defined as a 30% decrease in the sum of the longest diameter of the non-nodal target lesion from baseline. Each requires no new lesions present at evaluation. The proportion of participants with a response is provided here for each cohort. The proportion was calculated as the number of patients that had a best response of CR or PR divided by the number of patients evaluated for a response in each cohort.
Secondary Outcomes
- Incidence of Adverse Events(Every cycle of treatment, up to 3 years)
- Overall Survival(Time from registration to death, assessed up to 3 years)
- Time to Disease Progression(Time from registration to disease progression, assessed up to 3 years)
- Time to Treatment Failure(Time from study entry to the date patients end treatment, assessed up to 3 years)
- Duration of Response(Time from date at which the patient's objective status is first noted to be either a complete response (CR) or partial response (PR) to the date progression is documented, assessed up to 3 years)