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Trial · Interventional

CompletedPhase 2Results postedRegistry data

Everolimus and Octreotide Acetate With or Without Bevacizumab in Treating Patients With Locally Advanced or Metastatic Pancreatic Neuroendocrine Tumors That Cannot Be Removed by Surgery

NCTNCT01229943 (opens ClinicalTrials.gov in a new tab)Other idNCI-2011-02609Other idNCI-2011-02609Other idCDR0000687459Other idCALGB-80701

Overview

Status
Completed
Phase
Phase 2
Enrollment
150 participants (actual)
Sponsor
National Cancer Institute (NCI) · Nih
Design
Randomized · Open label (no masking)
Countries
2 countries

United States, Canada

Start
15 Oct 2010
Primary completion
1 Sept 2014
Completion
3 Jan 2018
First posted
28 Oct 2010 (estimated)
Last update posted
4 Aug 2022
Conditions
Advanced Pancreatic Neuroendocrine Tumor · Locally Advanced Pancreatic Neuroendocrine Tumor · Pancreatic Gastrinoma · Pancreatic Neuroendocrine Tumor G1 · Pancreatic Neuroendocrine Tumor G2 · Pancreatic Vipoma

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
20102012201420162018
  1. Ph 2

    Everolimus and Octreotide Acetate With or Without Bevacizumab in Treating Patients With Locally Advanced or Metastatic Pancreatic Neuroendocrine Tumors That Cannot Be Removed by Surgery

    NCT01229943

    15 Oct 2010 to 3 Jan 2018

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

This randomized phase II trial studies how well everolimus and octreotide acetate with or without bevacizumab works in treating patients with pancreatic neuroendocrine tumors that cannot be removed by surgery and have spread nearby or to other places in the body. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Octreotide acetate may interfere with and slow the growth of tumor cells. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Bevacizumab and everolimus also may stop the growth of pancreatic neuroendocrine tumors by blocking blood flow to the tumor. It is not yet known whether giving everolimus and octreotide acetate together is more effective with or without bevacizumab in treating pancreatic neuroendocrine tumors.

Interventions

  • BevacizumabBiological
  • EverolimusDrug
  • Octreotide AcetateDrug

Arms2

  • Experimental

    Arm I (octreotide acetate and everolimus)

    Patients receive 28-day cycles until progression or unacceptable toxicity consisting of: everolimus 10 mg PO QD on days 1-28 and octreotide acetate 20 mg IM on day 1.

  • Experimental

    Arm II (octreotide acetate, everolimus, and bevacizumab)

    Patients receive 28-day cycles until progression or unacceptable toxicity consisting of: everolimus 10 mg PO QD on days 1-28, octreotide acetate 20 mg IM on day 1 and bevacizumab 10 mg/kg IV on days 1 and 15.

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Progression Free Survival

    Time frame · From study entry to the date of documented progression or death from any cause, up to 3 years

    Registry description

    Progression Free Survival (PFS) was defined as the time from study entry until disease progression or death, whichever occurs first. The median PFS was estimated using the Kaplan-Meier method. Progression was assessed per RECIST criteria, and defined as at least a 20% increase in the sum of the longest diameters of target lesions (and an absolute increase of at least 0.5 cm) or the appearance of new lesions.

Secondary outcomes(2)
  1. Overall Response Rate

    Time frame · Up to 3 years

    Registry description

    The proportion of patients who respond (completely or partially) to each combination regimen will be estimated. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR): disappearance of all target lesions; Partial Response (PR) 30% decrease in sum of longest diameter of target lesions.

  2. Overall Survival (OS)

    Time frame · From registration to time of death, assessed up to 3 years

    Registry description

    Overall survival (OS) is defined as the time from study entry to death from any cause. The median OS was estimated using the Kaplan-Meier method.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMedian· From study entry to the date of documented progression or death from any cause, up to 3 years

Progression Free Survival

GroupValue (months)
Arm I (Octreotide Acetate and Everolimus)14.0
Arm II (Octreotide Acetate, Everolimus, and Bevacizumab)16.7
Secondary and other outcome results(2)
Secondary outcomeNumber· Up to 3 years

Overall Response Rate

GroupValue (percentage of participants)
Arm I (Octreotide Acetate and Everolimus)12
Arm II (Octreotide Acetate, Everolimus, and Bevacizumab)31
Secondary outcomeMedian· From registration to time of death, assessed up to 3 years

Overall Survival (OS)

GroupValue (months)
Arm I (Octreotide Acetate and Everolimus)35.0
Arm II (Octreotide Acetate, Everolimus, and Bevacizumab)36.7

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Arm I (Octreotide Acetate and Everolimus)Patients receive 28-day cycles until progression or unacceptable toxicity consisting of: everolimus 10 mg PO QD on days 1-28 and octreotide acetate 20 mg IM on day 1. Everolimus: Given PO Octreotide Acetate: Given IM–20 / 7473 / 74
Arm II (Octreotide Acetate, Everolimus, and Bevacizumab)Patients receive 28-day cycles until progression or unacceptable toxicity consisting of: everolimus 10 mg PO QD on days 1-28, octreotide acetate 20 mg IM on day 1 and bevacizumab 10 mg/kg IV on days 1 and 15. Bevacizumab: Given IV Everolimus: Given PO Octreotide Acetate: Given IM–31 / 7372 / 73

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: * Patients must have histologic documentation of well-differentiated or moderately differentiated neuroendocrine tumor from either a primary or metastatic site * If different histologic classification schemes are used, equivalent histologic classifications (for example "grade 1", "low-grade", or "intermediate-grade") are allowed * Patients with poorly differentiated neuroendocrine carcinoma or small cell carcinoma are excluded * Documentation from a metastatic disease site is sufficient if there is clinical evidence of a pancreatic primary site * Locally unresectable or metastatic disease * Patients must have either histologic documentation of a pancreatic primary site, or clinical evidence of a pancreatic neuroendocrine primary tumor as determined by the treating physician * Patients with neuroendocrine tumors (e.g., gastrinoma, VIPoma) in whom a pancreatic or peripancreatic primary site is strongly suspected are also eligible * Patients must have evidence of disease (measurable or non-measurable) with evidence of progression within the past 12 months * Measurable disease: Lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>= 2 cm with conventional techniques or as \>= 1 cm with spiral computed tomography (CT) scan * Non-measurable disease: All other lesions, including small lesions (longest diameter \< 20 mm with conventional techniques or \< 10 mm with spiral CT scan) and truly non-measurable lesions; lesions that are considered non-measurable include the following: * Bone lesions * Leptomeningeal disease * Ascites * Pleural/pericardial effusion * Inflammatory breast disease * Lymphangitis cutis/pulmonis * Abdominal masses that are not confirmed and followed by imaging techniques * Cystic lesions * No prior treatment with bevacizumab, everolimus, or other mammalian target of rapamycin (mTOR) inhibitors * Other prior treatments, including but not limited to prior cytotoxic chemotherapy, alpha interferon, tyrosine kinase inhibitors, external beam radiation therapy, and radiopeptide therapy are allowed * There is no limit on the number of prior treatment regimens * Any prior treatment (with the exception of octreotide) must be completed at least 4 weeks prior to initiation of treatment * Prior treatment with embolization or ablative therapies is allowed if measurable disease remains outside of the treated area * There is no limit on the prior number of procedures * Treatment with somatostatin analogs is a requirement of the study * Patients receiving octreotide at the time of study entry may continue at the same dose level for the duration of the study * Patients not receiving octreotide will initiate treatment according to study guidelines * Prior progression on somatostatin analogs or a negative octreotide scan does not exclude patient participation in this study * Patients should have completed any major surgery \>= 4 weeks from start of treatment * Patients must have completed any minor surgery \>= 2 weeks prior to start of treatment * Patients must have fully recovered from the procedure * Insertion of a vascular access device is not considered major or minor surgery * Patients should not receive immunization with attenuated live vaccines within one week prior to registration or during protocol therapy * No concurrent condition resulting in immune compromise, including chronic treatment with corticosteroids or other immuno suppressive agents * No active or severe liver disease (e.g., acute or chronic hepatitis, cirrhosis); no positive anti-hepatitis B virus (HBV); HBV seropositive patients (hepatitis B surface antigen \[HBsAg\] positive) are eligible if they are closely monitored for evidence of active HBV infection by HBV deoxyribonucleic acid (DNA) testing, and they agree to receive suppressive therapy with lamivudine or other HBV-suppressive therapy until at least 4 weeks after the last dose of everolimus; patients who are hepatitis C antibody positive are eligible provided that hepatitis C viral load (hepatitis C ribonucleic acid \[RNA\]) is undetectable * No clinical evidence of brain metastases or carcinomatous meningitis * No history of gastrointestinal (GI) perforation within 12 months prior to registration * No history of clinically significant bleeding episodes * Patients on therapeutic anticoagulation are eligible for the study provided that they are on a stable dose of anticoagulants * No uncontrolled diabetes mellitus * Patients with a history of severely impaired lung function as defined as spirometry and diffusing capacity of the lung for carbon monoxide (DLCO) that is 50% of the normal predicted value and/or oxygen (O2) saturation that is 88% or less at rest on room air are excluded * Patients with fasting serum cholesterol \>= 300 mg/dL OR \>= 7.75 mmol/L AND fasting triglycerides \>= 2.5 X upper limit of normal (ULN) should initiate lipid-lowering medications with the goal of achieving levels below these thresholds * No history of intolerance or allergies to octreotide * Patients with a history of hypertension must be adequately controlled (baseline blood pressure \[BP\] \< 150/90 mm Hg) on antihypertensives * No current congestive heart failure (New York Heart Association class II, III, or IV) * No symptomatic arterial peripheral vascular disease * No history of aortic aneurysm, aortic dissection, angina, myocardial infarction, stroke, or other arterial thrombotic events within 6 months of registration * Eastern Cooperative Oncology Group (ECOG) performance status 0-1 * Women must not be pregnant or lactating; both men and women of childbearing potential must be advised of the importance of using effective birth control measures during the course of the study * Granulocytes \>= 1,500/uL * Platelets \>= 100,000/uL * Creatinine =\< 1.5 x upper limit of normal * Bilirubin =\< 1.5 x upper limit of normal * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2.5 x upper limit of normal (=\< 5 x upper limit of normal if liver metastases present) * Urine protein =\< 1+ OR urine creatinine ratio =\< 1 (by urinalysis) * If urine protein creatinine (UPC) ratio is \> 1 on urinalysis, then 24-hour urine collection for protein must be obtained and level must be \< 1,000 mg for patient enrollment

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