Temsirolimus and Bevacizumab in Treating Patients With Advanced Endometrial, Ovarian, Liver, Carcinoid, or Islet Cell Cancer

Completed · Phase 2

Conditions studied: Adult Hepatocellular Carcinoma, Advanced Adult Hepatocellular Carcinoma, Endometrial Serous Adenocarcinoma, Localized Non-Resectable Adult Liver Carcinoma, Lung Carcinoid Tumor, Malignant Pancreatic Gastrinoma, Malignant Pancreatic Glucagonoma, Malignant Pancreatic Insulinoma, Malignant Pancreatic Somatostatinoma, Metastatic Digestive System Neuroendocrine Tumor G1, Ovarian Carcinosarcoma, Ovarian Endometrioid Adenocarcinoma, Ovarian Seromucinous Carcinoma, Ovarian Serous Surface Papillary Adenocarcinoma, Pancreatic Alpha Cell Adenoma, Pancreatic Beta Cell Adenoma, Pancreatic Delta Cell Adenoma, Pancreatic G-Cell Adenoma, Pancreatic Polypeptide Tumor, Recurrent Adult Liver Carcinoma, Recurrent Digestive System Neuroendocrine Tumor G1, Recurrent Fallopian Tube Carcinoma, Recurrent Ovarian Carcinoma, Recurrent Pancreatic Neuroendocrine Carcinoma, Recurrent Primary Peritoneal Carcinoma, Recurrent Uterine Corpus Carcinoma, Regional Digestive System Neuroendocrine Tumor G1, Stage IIIA Fallopian Tube Cancer, Stage IIIA Ovarian Cancer, Stage IIIA Primary Peritoneal Cancer, Stage IIIA Uterine Corpus Cancer, Stage IIIB Fallopian Tube Cancer, Stage IIIB Ovarian Cancer, Stage IIIB Primary Peritoneal Cancer, Stage IIIB Uterine Corpus Cancer, Stage IIIC Fallopian Tube Cancer, Stage IIIC Ovarian Cancer, Stage IIIC Primary Peritoneal Cancer, Stage IIIC Uterine Corpus Cancer, Stage IV Fallopian Tube Cancer, Stage IV Ovarian Cancer, Stage IV Primary Peritoneal Cancer, Stage IVA Uterine Corpus Cancer, Stage IVB Uterine Corpus Cancer, Uterine Carcinosarcoma

In brief

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.

Key facts

Study ID

NCT01010126

Run by

National Cancer Institute (NCI)

People needed

252

Starts

2009-09-08

Expected to finish

2017-03-13

Last updated by the study team

2019-01-25

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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
• Urinalysis < 2+ protein; urine protein should be screened by dipstick or urine analysis; for proteinuria >= 2+, 24-hour urine protein should be obtained and the level should be < 2 g for patient enrollment
• Fasting serum cholesterol =< 350 mg/dL (=< 9.0 mmol/L)
• Triglycerides =< 1.5 x ULN (mg/dL or mmol/L); patients with triglyceride levels > 1.5 x ULN can be started on lipid lowering agents and reevaluated within 1 week; if levels go to =< 1.5 x ULN, they can be considered for the trial and continue the lipid lowering agents; NOTE: cholesterol and triglyceride measurement and management are not required for single-agent bevacizumab cohort with islet cell carcinoma
• International normalized ratio (INR) =< 1.5 (unless the patient is on full dose warfarin)
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
• Capable of understanding the investigational nature, potential risks and benefits of the study and able to provide valid informed consent
• Negative serum pregnancy test done =< 7 days prior to registration, for women of childbearing potential only; NOTE: patients and their partners should be practicing an effective form of contraception during the study and for at least 3 months following the last dose of this combined therapy
• Full-dose anticoagulants, if a patient is receiving full-dose anticoagulants (except carcinoid tumors), the following criteria should be met for enrollment: the subject must have an in-range INR (usually between 2 and 3) on a stable dose of warfarin or on stable dose of low molecular weight (LMW) heparin
• Prior systemic treatments for metastatic disease are permitted, including targeted therapies, biologic response modifiers, chemotherapy, hormonal therapy, or investigational therapy; exception: in the case of endometrial cancer no prior chemotherapy for metastatic or recurrent disease is allowed; prior planned adjuvant chemotherapy is allowed
• Patients who have had prior anthracycline must have a normal ejection fraction on left ventricular ejection fraction (LVEF) assessment by multigated acquisition scan (MUGA) or echocardiogram (Echo) =< 4 weeks prior to registration
• Availability of tissue if applicable (from the primary tumor or metastases) for tumor studies for banking; Note: in the case of hepatocellular cancer if diagnosed by clinical and radiologic criteria only, availability of tissue not applicable
• Willingness to donate blood for biomarker studies related to the type of therapies used in this trial and the tumor types being treated
• ENDOMETRIAL CANCER (PERMANENTLY CLOSED TO ENROLLMENT)
• Any hormonal therapy directed at the malignant tumor is allowed; NOTE: therapy must be discontinued at least one week prior to registration
• Prior systemic therapy including biologic and immunologic agents as adjuvant treatment, must be discontinued at least 3 weeks prior to registration

You may not qualify if…

• 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
• Anticonvulsants (stable dose) are allowed
• Patients who had surgical resection of CNS metastases or brain biopsy =< 3 months prior to registration will be excluded
• Significant cardiovascular disease defined as congestive heart failure (New York Heart Association class II, III or IV), angina pectoris requiring nitrate therapy, or recent myocardial infarction (=< 6 months prior to registration)
• Uncontrolled hypertension (defined as a blood pressure of >= 150 mmHg systolic and/or >= 90 mmHg diastolic)
• Patient is on angiotensin-converting-enzyme (ACE) inhibitors (benazapril, captopril, enalopril, fosonopril, lisinopril, moexipril, perindopril, quinopril, ramipril, and trandolapril); (patients may have an alternate antihypertensive substituted); NOTE: ACE inhibitors are allowed in single agent bevacizumab cohort
• Currently active, second malignancy other than non-melanoma skin cancers; NOTE: patients are not considered to have a 'currently active' malignancy if they have completed anti-cancer therapy and are considered by their physician to be at less than 30% risk of relapse
• Any of the following, as this regimen may be harmful to a developing fetus or nursing child:
• Pregnant women
• Breastfeeding women
• Men or women of childbearing potential or their sexual partners who are unwilling to employ adequate contraception (diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, subcutaneous implants, or abstinence, etc.) NOTE: the effects of the agent(s) on the developing human fetus at the recommended therapeutic dose are unknown
• Known hypersensitivity to other recombinant human antibodies or Chinese hamster ovary cell products
• Other uncontrolled serious medical or psychiatric condition (e.g. cardiac arrhythmias, diabetes, etc.)
• Current therapy with a cytochrome P450 3A4 (CYP3A4) inhibitor or inducer; NOTE: these agents are allowed in the single-agent bevacizumab islet cell carcinoma cohort
• Active infection requiring antibiotics
• Active bleeding or pathological conditions that carry high risk of bleeding (e.g. tumor involving major vessels, known varices)

Where it is running

• Tower Cancer Research Foundation — Beverly Hills, California, United States
• City of Hope Comprehensive Cancer Center — Duarte, California, United States
• Los Angeles County-USC Medical Center — Los Angeles, California, United States
• USC / Norris Comprehensive Cancer Center — Los Angeles, California, United States
• University of California Davis Comprehensive Cancer Center — Sacramento, California, United States
• City of Hope South Pasadena — South Pasadena, California, United States
• University of Connecticut — Farmington, Connecticut, United States
• Hartford Hospital — Hartford, Connecticut, United States
• Mayo Clinic in Florida — Jacksonville, Florida, United States
• Moffitt Cancer Center — Tampa, Florida, United States
• Emory University/Winship Cancer Institute — Atlanta, Georgia, United States
• University of Chicago Comprehensive Cancer Center — Chicago, Illinois, United States
• Cancer Care Center of Decatur — Decatur, Illinois, United States
• Decatur Memorial Hospital — Decatur, Illinois, United States
• Crossroads Cancer Center — Effingham, Illinois, United States
• Ingalls Memorial Hospital — Harvey, Illinois, United States
• Memorial Medical Center — Springfield, Illinois, United States
• University of Iowa/Holden Comprehensive Cancer Center — Iowa City, Iowa, United States
• University of Maryland Saint Joseph Medical Center — Towson, Maryland, United States
• Fairview Ridges Hospital — Burnsville, Minnesota, United States
• Mercy Hospital — Coon Rapids, Minnesota, United States
• Fairview-Southdale Hospital — Edina, Minnesota, United States
• Unity Hospital — Fridley, Minnesota, United States
• Hutchinson Area Health Care — Hutchinson, Minnesota, United States
• Mayo Clinic in Arizona — Scottsdale, Arizona, United States

Full record on ClinicalTrials.gov

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