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CompletedNCT01010126Updated Jan 25, 2019Results posted

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

A Phase 2 interventional study of Bevacizumab and Temsirolimus in Adult Hepatocellular Carcinoma, Advanced Adult Hepatocellular Carcinoma and Endometrial Serous Adenocarcinoma, sponsored by National Cancer Institute (NCI). Completed at 61 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-01-25.

Sponsored by National Cancer Institute (NCI) · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
252
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

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
03

In context

Carcinoma

6,741 studies on the registry are indexed under Carcinoma; 1,163 are open to participants now.

This study's enrollment of 252 is above the median of 45 across 5,174 interventional studies indexed under Carcinoma.

Browse Carcinoma studies →

Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.

Of its 402 completed or terminated interventional studies of FDA-regulated products, 365 (91%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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
  • 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
  • Recurrent or persistent endometrial adenocarcinoma, uterine papillary serous carcinoma and carcinosarcoma which is refractory to curative therapy or established treatments; NOTE: histologic or cytologic confirmation of original primary tumor is required
  • HEPATOCELLULAR CANCER (PERMANENTLY CLOSED TO ENROLLMENT)
  • HCC confirmed by biopsy OR diagnosed by clinical and radiologic criteria; all of the following criteria must be met or a biopsy is required:

    • Known cirrhosis or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
    • Hypervascular liver masses > 2 cm, and either serum alpha-fetoprotein (AFP) > 400 ng/ml, or
    • AFP > three times normal and doubling in value in the antecedent 3 months
  • Child-Pugh A (=\< 6 points) or better liver status
  • Prior regional treatments for liver metastasis are permitted including:

    • Selective internal radiation therapy such as brachytherapy, cyberknife, radiolabeled microsphere embolization, etc.
    • Hepatic artery chemoembolization
    • Hepatic artery embolization
    • Hepatic artery infusional chemotherapy
    • Radiofrequency ablation NOTE: patients must be >= 4 weeks from treatment and show progressive disease in the liver after regional therapy or must have measurable disease outside the liver
  • Concomitant anti-viral therapy is allowed
  • History of prior varices or evidence of varices on pre-study CT/magnetic resonance imaging (MRI) imaging are required to undergo endoscopy =\< 4 weeks prior to registration; those who had received specific therapy (banding and/or sclerotherapy) and had not bled within the prior 6 months are eligible
  • Suitably recovered from prior localized therapy, in the opinion of the investigator
  • ISLET CELL CANCER AND CARCINOID TUMOR (PERMANENTLY CLOSED TO ENROLLMENT)
  • Patient has evidence of progressive disease as documented by Response Evaluation Criteria in Solid Tumors (RECIST) =\< 7 months prior to study entry
  • Carcinoid tumor cohort: prior and concurrent long-acting somatostatin analogue therapy is required; patient has to be on a stable dose of a long-acting somatostatin analogue >= 2 months prior to study entry with documentation of progressive disease on current dose
  • Islet cell tumor cohort: prior and/or concurrent long-acting somatostatin analogue therapy is allowed, but not required; if patient is continued on a long-acting somatostatin analogue, a stable dose for >= 2 months prior to study entry is required with documentation of progressive disease on current dose
  • Prior therapies allowed include:

    • =\< 2 prior chemotherapy regimens
    • Prior interferon >= 4 weeks prior to registration
    • Radiolabeled octreotide therapy (patients with prior radiolabeled octreotide therapy should have progressive disease after such therapy)
    • Other investigational therapy NOTE: islet Cell Single Agent Bevacizumab Cohort: Prior mammalian target of rapamycin (mTOR) inhibitor is allowed
  • Prior regional treatments for liver metastasis are permitted including:

    • Selective internal radiation therapy such as brachytherapy, cyberknife, radiolabeled microsphere embolization, etc.
    • Hepatic artery chemoembolization
    • Hepatic artery embolization
    • Hepatic artery infusional chemotherapy
    • Radiofrequency ablation NOTE: patients must be >= 12 weeks from treatment and show progressive disease in the liver after regional therapy or must have measurable disease outside the liver

Exclusion criteria

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

    • 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)
  • Known human immunodeficiency virus (HIV)-positive
  • ENDOMETRIAL CANCER (PERAMANENTLY CLOSED TO ENROLLMENT)
  • Received prior radiotherapy to any portion of the abdominal cavity or pelvis OTHER THAN for the treatment of endometrial cancer
  • Any chemotherapy for metastatic or recurrent cancer
  • Radiation therapy to > 25% of marrow bearing areas
  • HEPATOCELLULAR CANCER EXCLUSION (PERMANENTLY CLOSED TO ENROLLMENT)
  • Child-Pugh B or C classification
  • Grade >= 3 hemorrhage =\< 4 weeks prior to registration
  • Prior liver transplant with evidence of recurrent or metastatic disease
  • Patients on an active liver transplant list and considered likely to receive a liver transplant =\< 6 months following registration
  • Clinical evidence of encephalopathy
  • Prior treatment with sorafenib or other vascular endothelial growth factor (VEGF) inhibitors; NOTE: Exceptions allowed for patients unable to tolerate the agent; intolerance is defined in this protocol as a discontinued agent due to side effects with an exposure \< to 4 weeks of drug, at any dose level
  • OVARIAN CANCER (PERMANENTLY CLOSED TO ENROLLMENT)
  • Clinical signs and symptoms of gastrointestinal (GI) obstruction and require parental hydration/nutrition or tube feeding
  • Evidence of free abdominal air not explained by paracentesis or recent surgical procedures
  • Received more than two prior cytotoxic chemotherapy regimens for persistent or recurrent disease
  • CARCINOID (PERMANENTLY CLOSED TO ENROLLMENT)
  • Patients on anticoagulant therapy
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
252 participants (actual)

Study arms

  • Experimental
    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.

    Biological: Bevacizumab · Drug: Temsirolimus

Interventions

  • BiologicalBevacizumab

    Given IV

    Also known as: Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin, Bevacizumab Biosimilar BEVZ92, Bevacizumab Biosimilar BI 695502, Bevacizumab Biosimilar CBT 124, Bevacizumab Biosimilar FKB238, Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer, Recombinant Humanized Anti-VEGF Monoclonal Antibody, rhuMab-VEGF

  • DrugTemsirolimus

    Given IV

    Also known as: CCI-779, CCI-779 Rapamycin Analog, Cell Cycle Inhibitor 779, Rapamycin Analog, Rapamycin Analog CCI-779, Torisel

06

What researchers measure

Primary outcomes

  1. 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).

    Time frame: 6 months

  2. 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.

    Time frame: Up to 3 years

Secondary outcomes

  1. Duration of Response

    Duration of response is defined for all evaluable patients who have achieved a response as the date at which the patient's objective status is first noted to be either a CR or PR to the date progression is documented. Objective response was assessed using Response Evaluation Criteria In Solid Tumors (RECIST) as described in Primary Objective 2 in this report. Median duration of response and the confidence interval for the median duration will be computed.

    Time frame: 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

  2. Incidence of Adverse Events

    Adverse events are defined as events that are classified as either possibly, probably, or definitely related to study treatment, graded per National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0. The number of patients reporting grade 3 or higher adverse events at least possibly related to treatment are reported here. For a complete list of all reported adverse events, please see the adverse events section of this report.

    Time frame: Every cycle of treatment, up to 3 years

  3. Overall Survival

    Survival time will be defined as the time from registration to death. Time to event distributions will be estimated using the Kaplan-Meier method.

    Time frame: Time from registration to death, assessed up to 3 years

  4. Time to Disease Progression

    Time to progression is defined as the time from registration to disease progression. Patients who died without documentation of progression will be considered to have progressed on the date of their death. If a patient starts treatment and fails to return for evaluation, that patient will be censored for progression of disease at day one post-registration.

    Time frame: Time from registration to disease progression, assessed up to 3 years

  5. Time to Treatment Failure

    Time to treatment failure is defined as the time from study entry to the date patients end treatment.Time to treatment failure will be evaluated using the method of Kaplan-Meier.

    Time frame: Time from study entry to the date patients end treatment, assessed up to 3 years

07

Results

Posted Jan 25, 2019

Participant flow

Participant flow — Overall Study
MilestoneEndometrial CohortOvarian CohortHepatocellular CohortCarcinoid CohortIslet Cell (Double Agent) CohortIslet Cell (Bevacizumab-only) Cohort
Started275828575824
Completed265827575524
Not completed101030
Withdrew: Withdrawal by subject101030

Outcome measures

PrimaryProgression 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).

Time frame:
6 months
Reported as:
Number · proportion of patients
Progression Free Survival Rate
proportion of patientsEndometrial CohortOvarian CohortHepatocellular CohortCarcinoid CohortIslet Cell (Double Agent) CohortIslet Cell (Bevacizumab-only) Cohort
Progression Free Survival Rate0.52 (0.35 to 0.77)0.40 (0.29 to 0.55)0.71 (0.54 to 0.94)0.84 (0.75 to 0.95)0.85 (0.75 to 0.95)0.87 (0.74 to 1.00)
PrimaryTumor 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.

Time frame:
Up to 3 years
Reported as:
Number · proportion of participants
Tumor Response Rate
proportion of participantsEndometrial CohortOvarian CohortHepatocellular CohortCarcinoid CohortIslet Cell (Double Agent) CohortIslet Cell (Bevacizumab-only) Cohort
Tumor Response Rate0.31 (0.14 to 0.52)0.31 (0.20 to 0.45)0.19 (0.06 to 0.38)0.12 (0.05 to 0.24)0.40 (0.27 to 0.53)0.17 (0.05 to 0.37)
SecondaryDuration of Response

Duration of response is defined for all evaluable patients who have achieved a response as the date at which the patient's objective status is first noted to be either a CR or PR to the date progression is documented. Objective response was assessed using Response Evaluation Criteria In Solid Tumors (RECIST) as described in Primary Objective 2 in this report. Median duration of response and the confidence interval for the median duration will be computed.

Time frame:
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
Reported as:
Median · months
Duration of Response
monthsEndometrial CohortOvarian CohortHepatocellular CohortCarcinoid CohortIslet Cell (Double Agent) CohortIslet Cell (Bevacizumab-only) Cohort
Duration of Response25.1 (0 to 35.5)6.4 (3.7 to 10.8)6.4 (0 to 11.1)15.0 (0 to 18.8)11.3 (8.8 to 21.2)10.9 (3.7 to 34.1)
SecondaryIncidence of Adverse Events

Adverse events are defined as events that are classified as either possibly, probably, or definitely related to study treatment, graded per National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0. The number of patients reporting grade 3 or higher adverse events at least possibly related to treatment are reported here. For a complete list of all reported adverse events, please see the adverse events section of this report.

Time frame:
Every cycle of treatment, up to 3 years
Reported as:
Count of participants · Participants
Incidence of Adverse Events
ParticipantsEndometrial CohortOvarian CohortHepatocellular CohortCarcinoid CohortIslet Cell (Double Agent) CohortIslet Cell (Bevacizumab-only) Cohort
Grade 3 Adverse Event173224323613
Grade 4 Adverse Event160680
Grade 5 Adverse Event101200
SecondaryOverall Survival

Survival time will be defined as the time from registration to death. Time to event distributions will be estimated using the Kaplan-Meier method.

Time frame:
Time from registration to death, assessed up to 3 years
Reported as:
Median · months
Overall Survival
monthsEndometrial CohortOvarian CohortHepatocellular CohortCarcinoid CohortIslet Cell (Double Agent) CohortIslet Cell (Bevacizumab-only) Cohort
Overall Survival11.5 (6.5 to NA)16.3 (11.1 to 21.9)14.8 (9.7 to 18.1)32.7 (25.2 to 38.3)35.0 (14.6 to NA)NA (30.6 to NA)
SecondaryTime to Disease Progression

Time to progression is defined as the time from registration to disease progression. Patients who died without documentation of progression will be considered to have progressed on the date of their death. If a patient starts treatment and fails to return for evaluation, that patient will be censored for progression of disease at day one post-registration.

Time frame:
Time from registration to disease progression, assessed up to 3 years
Reported as:
Median · months
Time to Disease Progression
monthsEndometrial CohortOvarian CohortHepatocellular CohortCarcinoid CohortIslet Cell (Double Agent) CohortIslet Cell (Bevacizumab-only) Cohort
Time to Disease Progression6.0 (2.5 to 9.8)5.6 (4.3 to 6.4)8.0 (5.8 to 10.9)15.2 (11.4 to 24.2)13.1 (11.2 to 16.6)18.0 (10.6 to 37.0)
SecondaryTime to Treatment Failure

Time to treatment failure is defined as the time from study entry to the date patients end treatment.Time to treatment failure will be evaluated using the method of Kaplan-Meier.

Time frame:
Time from study entry to the date patients end treatment, assessed up to 3 years
Reported as:
Median · months
Time to Treatment Failure
monthsEndometrial CohortOvarian CohortHepatocellular CohortCarcinoid CohortIslet Cell (Double Agent) CohortIslet Cell (Bevacizumab-only) Cohort
Time to Treatment Failure3.8 (2.3 to 6.4)4.5 (2.7 to 5.6)6.5 (2.3 to 8.0)5.5 (4.4 to 8.1)11.3 (8.6 to 13.3)11.8 (5.8 to 18.0)

Adverse events

Collected over Adverse events were collected at the end of each 28 day cycle for a maximum of 58 cycles.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Endometrial Cohort2/26 (7.7%)16/26 (61.5%)26/26 (100%)
Ovarian Cohort1/58 (1.7%)34/58 (58.6%)58/58 (100%)
Hepatocellular Cohort3/27 (11.1%)13/27 (48.1%)27/27 (100%)
Carcinoid Cohort3/57 (5.3%)36/57 (63.2%)56/57 (98.2%)
Islet Cell (Double Agent) Cohort0/55 (0%)27/55 (49.1%)55/55 (100%)
Islet Cell (Bevacizumab-only) Cohort0/24 (0%)6/24 (25%)24/24 (100%)
Most frequent serious events
Showing 10 of 141
Most frequent serious events
EventEndometrial CohortOvarian CohortHepatocellular CohortCarcinoid CohortIslet Cell (Double Agent) CohortIslet Cell (Bevacizumab-only) Cohort
FatigueGeneral disorders0/262/584/273/571/550/24
Abdominal painGastrointestinal disorders2/265/583/278/576/550/24
ConfusionPsychiatric disorders0/260/583/272/571/550/24
DehydrationMetabolism and nutrition disorders2/263/581/275/571/550/24
Rectal painGastrointestinal disorders2/261/580/271/570/550/24
VomitingGastrointestinal disorders2/264/581/271/571/551/24
Urinary tract infectionInfections and infestations2/260/581/270/570/550/24
Serum cholesterol increasedInvestigations2/260/580/270/570/550/24
Protein urine positiveRenal and urinary disorders2/262/580/270/572/551/24
DyspneaRespiratory, thoracic and mediastinal disorders2/261/581/271/571/550/24
Most frequent other events
Showing 10 of 238
Most frequent other events
EventEndometrial CohortOvarian CohortHepatocellular CohortCarcinoid CohortIslet Cell (Double Agent) CohortIslet Cell (Bevacizumab-only) Cohort
Hemoglobin decreasedBlood and lymphatic system disorders20/2648/5823/2749/5749/558/24
Platelet count decreasedInvestigations16/2627/5822/2750/5741/557/24
HypertensionVascular disorders16/2634/5810/2739/5735/5521/24
FatigueGeneral disorders21/2643/5814/2740/5748/5512/24
Serum cholesterol increasedInvestigations22/2638/5812/2738/5746/557/24
Protein urine positiveRenal and urinary disorders14/2630/5817/2735/5737/5512/24
Leukocyte count decreasedInvestigations10/2630/5816/2738/5734/553/24
AnorexiaMetabolism and nutrition disorders16/2623/588/2727/5729/555/24
Serum triglycerides increasedMetabolism and nutrition disorders16/2625/587/2729/5732/551/24
Ear, nose and throat examination abnormalGastrointestinal disorders12/2618/584/2728/5733/553/24

Baseline characteristics

Age, Continuous
Age, Continuous(years)Endometrial CohortOvarian CohortHepatocellular CohortCarcinoid CohortIslet Cell (Double Agent) CohortIslet Cell (Bevacizumab-only) CohortTotal
Median60 (40 to 80)62.5 (35 to 82)59 (31 to 74)62 (35 to 89)58.5 (29 to 81)54.5 (40 to 78)60 (29 to 89)
Sex: Female, Male
Sex: Female, Male(Participants)Endometrial CohortOvarian CohortHepatocellular CohortCarcinoid CohortIslet Cell (Double Agent) CohortIslet Cell (Bevacizumab-only) CohortTotal
Female26585312910159
Male002226291491
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Endometrial CohortOvarian CohortHepatocellular CohortCarcinoid CohortIslet Cell (Double Agent) CohortIslet Cell (Bevacizumab-only) CohortTotal
Hispanic or Latino42201211
Not Hispanic or Latino195425545722231
Unknown or Not Reported3203008
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Endometrial CohortOvarian CohortHepatocellular CohortCarcinoid CohortIslet Cell (Double Agent) CohortIslet Cell (Bevacizumab-only) CohortTotal
American Indian or Alaska Native0000000
Asian0530008
Native Hawaiian or Other Pacific Islander0001001
Black or African American32268324
White224922495020212
More than one race0000000
Unknown or Not Reported1201015
Region of Enrollment
Region of Enrollment(participants)Endometrial CohortOvarian CohortHepatocellular CohortCarcinoid CohortIslet Cell (Double Agent) CohortIslet Cell (Bevacizumab-only) CohortTotal
Canada5348214063
United States212419554424187
08

Study locations

61 sites
  • 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
    Saint Louis, Missouri 63110, United States
  • Mercy Hospital Saint Louis
    Saint 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
  • Montefiore Medical Center - Moses Campus
    Bronx, New York 10467-2490, 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
  • 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
09

References and documents

Publications

  • Hobday 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. PubMed 25488966 ↗
  • Knox 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. PubMed 25318437 ↗

Study documents

  • Protocol and statistical analysis plan · Sep 6, 2016

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jan 25, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01010126
Lead sponsor
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Nov 9, 2009
Start date
Sep 8, 2009
Primary completion
Mar 13, 2017
Completion
Mar 13, 2017
Results posted
Jan 25, 2019
Last update
Jan 25, 2019

Study contacts

Henry Pitot
principal investigator · Mayo Clinic

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Jan 2019. You cannot join it, but the record below documents what was studied.

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