A Randomized, Double-blind, Multicenter, Phase III Study of Everolimus (RAD001) Plus Best Supportive Care Versus Placebo Plus Best Supportive Care in the Treatment of Patients With Advanced NET of GI or Lung Origin
Description
Brief Summary
The purpose of this study is to compare the antitumor activity of everolimus plus best
supportive care versus placebo plus best supportive care in patients with progressive
nonfunctional neuroendocrine tumor (NET) of gastrointestinal (GI) or lung origin without a
history of, or current symptoms of carcinoid syndrome.
Detailed Description
This was a prospective, multi-center, randomized, double-blind, parallel-group,
placebo-controlled, two-arm Phase III study comparing the efficacy and safety of everolimus
10 mg daily to placebo in patients with advanced NET of GI or lung origin without a history
of, or current symptoms of carcinoid syndrome.
After assessment of eligibility, participants qualifying for the study were randomized in a
2:1 ratio to receive either everolimus or matching placebo. Participants received daily oral
doses of 10 mg everolimus or matching placebo as study drug. In both arms, the study drug was
combined with best supportive care and treatment cycles were defined as 28 days. Participants
were treated until disease progression as per Response Evaluation Criteria In Solid Tumors
(RECIST) 1.0, intolerable toxicity, death, lost to follow-up or consent withdrawal.
Regardless of the reason for study drug discontinuation, participants had a safety follow-up
visit scheduled 30 days after the last dose of the study drug.
Per data monitoring committee recommendation, all participants on treatment with placebo were
allowed to crossover to open-label treatment with everolimus. This change was implemented
through protocol amendment 3 (issued on 06-May-2016) after which remaining participants
entered into open-label phase of the study.
Phase
Phase 3 - a treatment has shown activity against a particular disease, where it is either added to existing treatment or compared to the standard treatment.Inclusion and Exclusion Criteria
- Pathologically confirmed, well differentiated (G1 or G2), advanced (unresectable or metastatic), neuroendocrine tumor of GI or lung origin
- No history of and no active symptoms related to carcinoid syndrome
- In addition to treatment-naive patients, patients previously treated with SSA, Interferon (IFN), one prior line of chemotherapy, and/or PRRT were allowed into the study. Pretreated patients had to have progressed on or after the last treatment
- Radiological documented disease progression within 6 months prior to randomization
- Measurable disease
- WHO performance status ≤1
- Adequate bone marrow, liver and renal function
- Patients with poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, pancreatic islet cell carcinoma, insulinoma, glucagonoma, gastrinoma, goblet cell carcinoid, large cell neuroendocrine carcinoma and small cell carcinoma
- Patients with pancreatic NET or NET of origins other than GI or Lung
- Patients with history of or active symptoms of carcinoid syndrome (e.g. flushing, diarrhea)
- Patients with more than one line of prior chemotherapy
- Prior targeted therapy
- Hepatic intra-arterial embolization within the last 6 months. Cryoablation or radiofrequency ablation of hepatic metastases within 2 months of randomization
- Prior therapy with mTOR inhibitors (e.g. sirolimus, temsirolimus, deforolimus)
- Known intolerance or hypersensitivity to everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus)
- Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus
- Uncontrolled diabetes mellitus as defined by HbA1c >8% despite adequate therapy
- Patients who had any severe and/or uncontrolled medical conditions such as:
- unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤6 months prior to randomization, serious uncontrolled cardiac arrhythmia
- active or uncontrolled severe infection
- liver disease such as cirrhosis, decompensated liver disease, and chronic hepatitis (i.e. quantifiable HBV-DNA and/or positive HbsAg, quantifiable HCV-RNA)
- Chronic treatment with corticosteroids or other immunosuppressive agents
- Known history of HIV seropositivity
- Pregnant or nursing (lactating) women Other protocol-defined inclusion/exclusion criteria might apply.
Sites
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California
- USC/Kenneth Norris Comprehensive Cancer Center USC/Norris, Los Angeles, California, 90033
- Cedars Sinai Medical Center SC, Los Angeles, California, 90048
- Scripps Clinic Regulatory, La Jolla, California, 92121
-
Oregon
- Oregon Health & Science University OH&SU, Portland, Oregon, 97239
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Colorado
- University of Colorado SC, Aurora, Colorado, 80045
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Texas
- Texas Oncology, P.A. TX Onc Baylor, Dallas, Texas, 75251
- Texas Oncology, P.A. Texas Oncology - Amarillo, Dallas, Texas, 75251
- Texas Oncology Texas Oncology - Amarillo, Dallas, Texas, 75251
- Texas Oncology TX Oncology Baylor, Dallas, Texas, 75251
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Illinois
- University of Chicago Medical Center UC SC, Chicago, Illinois, 60546
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Tennessee
- Vanderbilt University Medical Center Vanderbilt Med Ctr, Nashville, Tennessee, 37232
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Indiana
- Indiana University Health Goshen Center for Cancer IU Health - SC, Indianapolis, Indiana, 46202
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Italy
- Novartis Investigative Site, Napoli, 80132
- Novartis Investigative Site, Napoli, 80131
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Czech Republic
- Novartis Investigative Site, Brno, 65653
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FI
- Novartis Investigative Site, Firenze, FI, 50134
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Germany
- Novartis Investigative Site, Magdeburg, 39120