Temsirolimus and Bevacizumab in Treating Patients With Advanced Endometrial, Ovarian, Liver, Carcinoid, or Islet Cell Cancer
A Phase 2 Trial of Temsirolimus and Bevacizumab in Patients With Endometrial, Ovarian, Hepatocellular Carcinoma, Carcinoid or Islet Cell Cancer
23 other identifiers
interventional
252
2 countries
61
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Sep 2009
Longer than P75 for phase_2
61 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
September 8, 2009
CompletedFirst Submitted
Initial submission to the registry
November 6, 2009
CompletedFirst Posted
Study publicly available on registry
November 9, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 13, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
March 13, 2017
CompletedResults Posted
Study results publicly available
January 25, 2019
CompletedJanuary 25, 2019
January 1, 2019
7.5 years
November 6, 2009
September 20, 2018
January 24, 2019
Conditions
Outcome Measures
Primary Outcomes (2)
Progression Free Survival Rate
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).
6 months
Tumor Response Rate
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.
Up to 3 years
Secondary Outcomes (5)
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
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
Study Arms (1)
Treatment (temsirolimus, bevacizumab)
EXPERIMENTALPatients 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.
Interventions
Given IV
Given IV
Eligibility Criteria
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
- +41 more criteria
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
- +27 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (61)
Mayo Clinic in Arizona
Scottsdale, Arizona, 85259, United States
Tower Cancer Research Foundation
Beverly Hills, California, 90211-1850, United States
City of Hope Comprehensive Cancer Center
Duarte, California, 91010, United States
Los Angeles County-USC Medical Center
Los Angeles, California, 90033, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
City of Hope South Pasadena
South Pasadena, California, 91030, United States
University of Connecticut
Farmington, Connecticut, 06030, United States
Hartford Hospital
Hartford, Connecticut, 06102, United States
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
Emory University/Winship Cancer Institute
Atlanta, Georgia, 30322, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
Cancer Care Center of Decatur
Decatur, Illinois, 62526, United States
Decatur Memorial Hospital
Decatur, Illinois, 62526, United States
Crossroads Cancer Center
Effingham, Illinois, 62401, United States
Ingalls Memorial Hospital
Harvey, Illinois, 60426, United States
Memorial Medical Center
Springfield, Illinois, 62781, United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242, United States
University of Maryland Saint Joseph Medical Center
Towson, Maryland, 21204, United States
Fairview Ridges Hospital
Burnsville, Minnesota, 55337, United States
Mercy Hospital
Coon Rapids, Minnesota, 55433, United States
Fairview-Southdale Hospital
Edina, Minnesota, 55435, United States
Unity Hospital
Fridley, Minnesota, 55432, United States
Hutchinson Area Health Care
Hutchinson, Minnesota, 55350, United States
Minnesota Oncology Hematology PA-Maplewood
Maplewood, Minnesota, 55109, United States
Saint John's Hospital - Healtheast
Maplewood, Minnesota, 55109, United States
Abbott-Northwestern Hospital
Minneapolis, Minnesota, 55407, United States
Hennepin County Medical Center
Minneapolis, Minnesota, 55415, United States
North Memorial Medical Health Center
Robbinsdale, Minnesota, 55422, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
Metro Minnesota Community Oncology Research Consortium
Saint Louis Park, Minnesota, 55416, United States
Park Nicollet Clinic - Saint Louis Park
Saint Louis Park, Minnesota, 55416, United States
Regions Hospital
Saint Paul, Minnesota, 55101, United States
United Hospital
Saint Paul, Minnesota, 55102, United States
Saint Francis Regional Medical Center
Shakopee, Minnesota, 55379, United States
Lakeview Hospital
Stillwater, Minnesota, 55082, United States
Ridgeview Medical Center
Waconia, Minnesota, 55387, United States
Rice Memorial Hospital
Willmar, Minnesota, 56201, United States
Minnesota Oncology Hematology PA-Woodbury
Woodbury, Minnesota, 55125, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Mercy Hospital Saint Louis
St Louis, Missouri, 63141, United States
Billings Clinic Cancer Center
Billings, Montana, 59101, United States
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, 07920, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065, United States
Weill Medical College of Cornell University
New York, New York, 10065, United States
Memorial Sloan Kettering Sleepy Hollow
Sleepy Hollow, New York, 10591, United States
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467-2490, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599, United States
Case Western Reserve University
Cleveland, Ohio, 44106, United States
Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia, 23298, United States
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton, Ontario, L8V 5C2, Canada
London Regional Cancer Program
London, Ontario, N6A 4L6, Canada
Trillium Health Partners - Credit Valley Hospital
Mississauga, Ontario, L5M 2N1, Canada
University Health Network-Princess Margaret Hospital
Toronto, Ontario, M5G 2M9, Canada
Related Publications (3)
Abuzakhm SM, Sukrithan V, Fruth B, Qin R, Strosberg J, Hobday TJ, Semrad T, Reidy-Lagunes D, Kindler HL, Kim GP, Knox JJ, Kaubisch A, Villalona-Calero M, Chen H, Erlichman C, Shah MH. A phase II study of bevacizumab and temsirolimus in advanced extra-pancreatic neuroendocrine tumors. Endocr Relat Cancer. 2023 Sep 13;30(11):e220301. doi: 10.1530/ERC-22-0301. Print 2023 Nov 1.
PMID: 37702588DERIVEDHobday TJ, Qin R, Reidy-Lagunes D, Moore MJ, Strosberg J, Kaubisch A, Shah M, Kindler HL, Lenz HJ, Chen H, Erlichman C. Multicenter Phase II Trial of Temsirolimus and Bevacizumab in Pancreatic Neuroendocrine Tumors. J Clin Oncol. 2015 May 10;33(14):1551-6. doi: 10.1200/JCO.2014.56.2082. Epub 2014 Dec 8.
PMID: 25488966DERIVEDKnox JJ, Qin R, Strosberg JR, Tan B, Kaubisch A, El-Khoueiry AB, Bekaii-Saab TS, Rousey SR, Chen HX, Erlichman C. A phase II trial of bevacizumab plus temsirolimus in patients with advanced hepatocellular carcinoma. Invest New Drugs. 2015 Feb;33(1):241-6. doi: 10.1007/s10637-014-0169-3. Epub 2014 Oct 16.
PMID: 25318437DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Henry Pitot, M.D.
- Organization
- Mayo Clinic
Study Officials
- PRINCIPAL INVESTIGATOR
Henry Pitot
Mayo Clinic
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 6, 2009
First Posted
November 9, 2009
Study Start
September 8, 2009
Primary Completion
March 13, 2017
Study Completion
March 13, 2017
Last Updated
January 25, 2019
Results First Posted
January 25, 2019
Record last verified: 2019-01