Everolimus and Octreotide in Patients With Advanced Carcinoid Tumor
This study is ongoing, but not recruiting participants.
Sponsor:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00412061
First received: December 13, 2006
Last updated: May 11, 2012
Last verified: May 2012
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Purpose
The purpose of this study was to evaluate whether everolimus 10 mg / day added to treatment with depot octreotide prolongs progression free survival compared to treatment with octreotide alone in patients with advanced carcinoid tumor.
| Condition | Intervention | Phase |
|---|---|---|
|
Carcinoid Tumor Malignant Carcinoid Syndrome |
Drug: Everolimus Drug: Octreotide Drug: Placebo |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment |
| Official Title: | A Randomized, Double-blind Placebo-controlled, Multicenter Phase III Study in Patients With Advanced Carcinoid Tumor Receiving Octreotide Depot and Everolimus 10 mg/Day or Octreotide Depot and Placebo |
Resource links provided by NLM:
Further study details as provided by Novartis:
Primary Outcome Measures:
- Progression Free Survival (PFS) as Per Adjudicated Central Radiology Review [ Time Frame: Time from randomisation to dates of disease progression, death from any cause or last tumor assessment, reported between day of first patient randomised, 10 January 2007, until cut-off date 02 April 2010 ] [ Designated as safety issue: No ]Progression free survival (PFS) is defined as the time from randomization to the date of first documented disease progression or death from any cause. The primary analysis of PFS was based on the independent central adjudicated assessment using Kaplan-Meier method.
Secondary Outcome Measures:
- Best Overall Response Rate as Per Adjudicated Central Radiology Review Based on Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Time from randomisation to dates of disease progression, death from any cause or last tumor assessment, reported between day of first patient randomised, 10 January 2007, until cut-off date 02 April 2010 ] [ Designated as safety issue: No ]The best overall response rate is defined as the percentage of patients having achieved confirmed Complete Response + Partial Response. Complete Response (CR) = at least two determinations of CR at least 4 weeks apart before progression. • Partial response (PR) = at least two determinations of PR or better at least 4 weeks apart before progression.
- Number of Patients With Adverse Events (AEs), Clinically Notable AE, Death, Serious Adverse Events (SAEs) [ Time Frame: From first day of treatment up to 28 days after last day of treatment in double blind (safety data collected till data cut off date i.e. 2nd April 2010) ] [ Designated as safety issue: Yes ]AEs are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. SAEs are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.
- Progression Free Survival (PFS) as Per Adjudicated Central Review by Change From Baseline Chromogranin A (CgA) and 5-hydroxyindoleacetic Acid (5-HIAA) [ Time Frame: If elevated at baseline, evaluated every cycle visit (28 days/cycle) ] [ Designated as safety issue: No ]Serum CgA and 5-HIAA levels in urine are frequently elevated in patients with advanced carcinoid tumors. Baseline levels of serum CgA were characterized relative to the upper limited of normal (ULN). CgA levels exceeding 2 x ULN were considered to be 'Elevated'; otherwise considered as "Non-elevated". Baseline levels of 5-HIAA in urine were defined as 'High' if they exceeded the median value, and 'Low' if they were lower than or equal to the median.
- Overall Survival Using Kaplan-Meier Methodology [ Time Frame: The date of randomization to the date of death ] [ Designated as safety issue: No ]Overall survival was defined as the time from the date of randomization to the date of death from any cause. If a patient was not known to have died, survival was censored at the date of last contact. Kaplan-Meier methodology was used to estimate the median overall survival for each treatment group.
- Evaluation of Pharmacokinetics (PK)Parameters [ Time Frame: Day 1 of every cycle (28 days/cycle) throughout the study ] [ Designated as safety issue: No ]The PK parameters for a full PK profile at steady-state were determined in blood using non compartmental methods. The PK parameters were: area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC0-t last), area under the concentration time curve from time zero to time t, where t is the end of the dosing interval (AUC0-t), maximum (peak) drug concentration (Cmax), time to maximum (peak) drug concentration (tmax), and minimum (trough) drug concentration (Cmin).
| Enrollment: | 429 |
| Study Start Date: | January 2007 |
| Estimated Study Completion Date: | January 2013 |
| Primary Completion Date: | April 2010 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Octreotide+ Everolimus
Everolimus was administered in accordance with a 10-mg daily dosing regimen (two 5-mg tablets) in conjunction with octreotide 30 mg intramuscularly (i.m.) every 28 days. Patients were treated until progression or unacceptable toxicity. Each treatment cycle lasted 28 days. Patients received their first dose of everolimus at Cycle 1, Day 1. Administration of octreotide was performed every 28 days (± 4 days) starting on Cycle 1, Day 1.
|
Drug: Everolimus
A 10-mg oral daily dosing regimen (two 5-mg tablets) of everolimus.
Other Name: RAD001
Drug: Octreotide
Octreotide 30 mg intramuscularly (i.m.) every 28 days.
Other Name: Sandostatin LAR® Depot
|
|
Placebo Comparator: Octreotide+ Placebo
Matching placebo was administered in accordance with a 10-mg daily dosing regimen (two 5-mg tablets) in conjunction with octreotide 30 mg intramuscularly (i.m.) every 28 days. Patients were treated until progression or unacceptable toxicity; Each treatment cycle lasted 28 days. Patients received their first dose of matching placebo at Cycle 1, Day 1. Administration of octreotide was performed every 28 days (± 4 days) starting on Cycle 1 Day 1.
|
Drug: Octreotide
Octreotide 30 mg intramuscularly (i.m.) every 28 days.
Other Name: Sandostatin LAR® Depot
Drug: Placebo
A 10-mg oral daily dosing regimen (two 5-mg tablets) of matching placebo.
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion criteria:
- Advanced (unresectable or metastatic) carcinoid tumor
- Confirmed low-grade or intermediate-grade neuroendocrine carcinoma
- Documented progression of disease within 12 months prior to randomization.
- Measurable disease determined by triphasic computer tomography (CT) scan or magnetic resonance imaging (MRI).
Exclusion criteria:
- Poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, goblet cell carcinoma, or small cell carcinoma.
- Hepatic artery embolization within the last 6 months or cryoablation of hepatic metastasis within 2 months of enrollment.
- Previous treatment with mammalian target of rapamycin (mTOR) inhibitors (sirolimus, temsirolimus, everolimus)
- Intolerance or hypersensitivity to octreotide, everolimus, or other rapamycins.
- Severe or uncontrolled medical conditions
- Chronic treatment with corticosteroids or other immunosuppressive agent.
- Other primary cancer within 3 years.
Other protocol-defined inclusion/exclusion criteria applied
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00412061
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| United States, Arizona | |
| University of Arizona-Arizona Cancer Center | |
| Tucson, Arizona, United States, 85724 | |
| United States, Arkansas | |
| Highlands Oncology Group, PA | |
| Fayetteville, Arkansas, United States, 72703 | |
| Hematology, Oncology Services of Arkansas (H.O.S.A.) | |
| Little Rock, Arkansas, United States, 72205 | |
| United States, California | |
| Pacific Cancer Medical Center, Inc. | |
| Anaheim, California, United States, 92801 | |
| UCLA Jonsson Comprehensive Cancer Center | |
| Los Angeles, California, United States, 90095 | |
| Outpatient Cancer Center at the Samuel Oschin Comprehensive Cancer Institute | |
| Los Angeles, California, United States, 90048 | |
| United States, Colorado | |
| University of Colorada Health Sciences Center | |
| Aurora, Colorado, United States, 80045 | |
| USO | |
| Denver, Colorado, United States, 80218 | |
| United States, Connecticut | |
| Eastern Connecticut Hematology & Oncology Associates | |
| Norwich, Connecticut, United States, 06360 | |
| Cancer Center of Central Connecticut | |
| Southington, Connecticut, United States, 06489 | |
| Oncology, PC | |
| Stamford, Connecticut, United States, 06902 | |
| United States, Florida | |
| Ocala Oncology | |
| Ocala, Florida, United States, 34474 | |
| H. Lee Moffitt Cancer Center & Research Institute | |
| Tampa, Florida, United States, 33612 | |
| United States, Illinois | |
| US Oncology | |
| Arlington Heights, Illinois, United States, 60005 | |
| United States, Indiana | |
| Indiana University Cancer Center | |
| Indianapolis, Indiana, United States, 46202 | |
| US Oncology | |
| Indianapolis, Indiana, United States, 46227 | |
| United States, Iowa | |
| University of Iowa Medical Center | |
| Iowa City, Iowa, United States, 52242 | |
| United States, Kansas | |
| University of Kansas Hospital | |
| Kansas City, Kansas, United States, 66160 | |
| Kansas City Cancer Center (Southwest) | |
| Overland Park, Kansas, United States, 66210 | |
| United States, Kentucky | |
| Louisville Oncology Research Program | |
| Lousville, Kentucky, United States, 40202 | |
| United States, Louisiana | |
| Louisiana State University Health Sciences Center | |
| Kenner, Louisiana, United States, 70065 | |
| United States, Minnesota | |
| Mayo Clinic Division of Medical Oncology | |
| Rochester, Minnesota, United States, 55905 | |
| United States, Missouri | |
| Washington University School of Medicine-Siteman Cancer Center | |
| St. Louis, Missouri, United States, 63110 | |
| Care and Research | |
| St. Louis, Missouri, United States, 63141 | |
| United States, New Hampshire | |
| Hitchcock Medical Center | |
| Lebanon, New Hampshire, United States, 03756 | |
| United States, New York | |
| York Oncology Hematology | |
| Albany, New York, United States, 12208 | |
| NYU Cancer Institute | |
| New York, New York, United States, 10016 | |
| United States, North Carolina | |
| Duke University Medical Center | |
| Durham, North Carolina, United States, 27710 | |
| United States, Ohio | |
| University Hospitals of Cleveland-Ireland Cancer Center | |
| Cleveland, Ohio, United States, 44106 | |
| Greater Dayton Cancer Center | |
| Kettering, Ohio, United States, 45409 | |
| United States, Pennsylvania | |
| Fox Chase Cancer Center | |
| Philadelphia, Pennsylvania, United States, 19111 | |
| United States, South Carolina | |
| Medical University of South Carolina Hollings Cancer Center | |
| Charleston, South Carolina, United States, 29425 | |
| Cancer Centers of the Carolinas | |
| Greenville, South Carolina, United States, 29615 | |
| United States, Tennessee | |
| Sarah Cannon Research Institute | |
| Nashville, Tennessee, United States, 37203 | |
| United States, Texas | |
| US Oncology - Texas Oncology P.A. | |
| Austin, Texas, United States, 78731 | |
| South Texas Cancer Center | |
| Corpus Christi, Texas, United States, 78405 | |
| US Oncology/Sammons Cancer Center | |
| Dallas, Texas, United States, 75246 | |
| US Oncology - Texas Oncology 12th Avenue | |
| Fort Worth, Texas, United States, 76104 | |
| MD Anderson Cancer Center | |
| Houston, Texas, United States, 77030 | |
| Scott & White Hospital | |
| Temple, Texas, United States, 76508 | |
| Tyler Cancer Center | |
| Tyler, Texas, United States, 75702 | |
| United States, Virginia | |
| Virginia Oncology Associates | |
| Norfolk, Virginia, United States, 23502 | |
| United States, Washington | |
| US Oncology | |
| Vancouver, Washington, United States, 98684 | |
| United States, Wisconsin | |
| University of Wisconsin Comprehensive Cancer Center | |
| Madison, Wisconsin, United States, 53792 | |
| Australia | |
| Novartis Investigative Site | |
| East Melbourne, Australia, 3002 | |
| Novartis Investigative Site | |
| Heidelburg, Australia, 3084 | |
| Novartis Investigative Site | |
| Herston, Australia, 4029 | |
| Novartis Investigative Site | |
| Woodville, Australia, 5011 | |
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
| Study Director: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
More Information
Additional Information:
No publications provided by Novartis
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Novartis ( Novartis Pharmaceuticals ) |
| ClinicalTrials.gov Identifier: | NCT00412061 History of Changes |
| Other Study ID Numbers: | CRAD001C2325 |
| Study First Received: | December 13, 2006 |
| Results First Received: | October 25, 2011 |
| Last Updated: | May 11, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Novartis:
|
Cancer Carcinoid Tumor Neuroendocrine |
Carcinoma Everolimus Octreotide |
Additional relevant MeSH terms:
|
Carcinoid Tumor Malignant Carcinoid Syndrome Serotonin Syndrome Neuroendocrine Tumors Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Adenocarcinoma Carcinoma Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Drug Toxicity Poisoning Substance-Related Disorders |
Octreotide Sirolimus Everolimus Antineoplastic Agents, Hormonal Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Gastrointestinal Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antibiotics, Antineoplastic Antifungal Agents Anti-Infective Agents Anti-Bacterial Agents |
ClinicalTrials.gov processed this record on May 21, 2013