RAMSETE: RAD001 in Advanced and Metastatic Silent Neuro-endocrine Tumors in Europe

NCT00688623 | Completed Phase 2 Results

• 1 other identifier: CRAD001CDE16
• Study Type: interventional
• Target: 73
• Locations: 8 countries
• Sites: 40

Brief Summary

To evaluate the preliminary efficacy and safety of RAD001 as monotherapy for first-line treatment of patients with metastatic papillary carcinoma of the kidney.

Conditions

Advanced and Metastatic Silent Neuro-Endocrine Tumors; Carcinoma; Neuroendocrine; Non Functioning Neuroendocrine Tumors (NETs); Non Syndromic Neuroendocrine Tumors; Carcinoids; Non Functioning

Keywords

Neuroendocrine tumors; non functioning neuroendocrine tumors; Non syndromic neuroendocrine tumors; carcinoids; non-functioning carcinoids; adults; everolimus; NET; RAMSETE; CRAD001; non-functioning neuroendocrine tumors carcinoids

Outcome Measures

Primary Outcomes (4)

• Percentage of Participants' Best Overall Response Rate at 12 Months - Per Protocol Set (PP)

  Overall response rate (ORR) was based on RECIST central assessment and defined as the percentage of patients with best overall response (BOR) of a confirmed complete response (CR) or partial response (PR). The BOR was calculated on basis of the tumor of overall lesion response evaluated at each visit. To be assigned a status of PR or CR, changes in tumor measurements had to be confirmed by repeat assessments obtained within 4 weeks after the criteria for response were first met. Assessments was based on RECIST criteria 1.0. Measurable disease lesions had to be accurately measured in at least one dimension with longest diameter ≥ 20 mm using conventional techniques or ≥ 10 mm with spiral CT scan (with minimum lesion size no less than double the slice thickness). PR required at least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the baseline sum of the longest diameters. CR required disappearance of all target and non-target lesions.

  baseline up to approximately 12 months

• Percentage of Participants With Objective Response Rate at 12 Months - Per Protocol Set (PP)

  Overall Response Rate (ORR) was calculated for total PP population based on central review as confirmatory, primary analysis as well as for ITT population as sensitivity analysis. It was presented with relative frequencies and the exact 2-sided 80% confidence limit (CI) computed using the Clopper-Pearson method). If the lower limit of the CI did not include p0=5%, the hypothesis that p ≤ 5% was rejected. The primary analysis was based on the PP Set

  baseline up to approximately 12 months

• Percentage of Participants With a Overall Response Rate With a Complete Response (CR) or Partial Response (PR) at 12 Months ITT Set

  The best overall response (BOR) was calculated on basis of the tumor of overall lesion response evaluated at each visit. To be assigned a status of PR or CR, changes in tumor measurements had to be confirmed by repeat assessments that should have been performed not less than 4 weeks after the criteria for response were first met. Assessments was based on RECIST criteria 1.0. Measurable disease lesions had to be accurately measured in at least one dimension with longest diameter ≥ 20 mm using conventional techniques or ≥ 10 mm with spiral CT scan (with minimum lesion size no less than double the slice thickness). PR required at least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the baseline sum of the longest diameters. CR required disappearance of all target and non-target lesions.

  baseline up to approximately 12 months

• Percentage of Participants With Objective Response Rate at 12 Months ITT Set

  Overall Response Rate (ORR) was presented for ITT population as sensitivity analysis. It was presented with relative frequencies and the exact 2-sided 80% confidence limit (CL; computed using the Clopper-Pearson method). If the lower limit of the CI did not include p0=5%, the hypothesis that p ≤ 5% was rejected.

  baseline up to approximately 12 months

Secondary Outcomes (4)

• Percentage of Participants With Disease Control Rate (DCR) at 12 Months for Per Protocol (PP) and ITT Sets

  baseline up to approximately 12 months

• Percentage of Participants' Biochemical Response Rate Based on the Tumor Marker Chromogranin A (CgA)

  baseline up to approximately 12 months

• Duration of Progression Free Survival (PFS) for Per Protocol (PP) and ITT Sets

  baseline up to approximately 12 months

• Overall Survival (OS) for Per Protocol (PP) and ITT Sets

  baseline up to approximately 15 months

Study Arms (1)

Everolimus

EXPERIMENTAL

Everolimus

Drug: Everolimus

Interventions

Everolimus DRUG

Everolimus 5 mg tablets were supplied in blister packs

Everolimus

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 18 years old
• Patients with advanced (unresectable or metastatic) biopsy proven non-syndromic neuro-endocrine carcinoma, low or intermediate grade
• Radiological documentation of disease progression within 12 months prior to study entry. If patients received anti-tumor therapy during the past 12 months, they must have radiological documentation of progressive disease (PD) while on or after receiving the therapy
• Patients may have received previous treatments (chemotherapy, biotherapy, peptide-receptor radionuclide therapy); an overall maximum of 3 systemic treatment is allowed
• Patients with at least one measurable lesion
• Patients with an ECOG (Eastern Cooperative Oncology Group) Performance Status 0-2
• Adequate bone marrow function
• Adequate liver function
• Adequate renal function
• Adequate lipid profile

You may not qualify if:

• Patients with poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, goblet cell carcinoid and small cell carcinoma
• Patients with carcinoid with hormone related symptoms (diarrhea ≥ 4 stools per day and/or flushes)
• Patients with Islet cell carcinomas or pancreatic NET
• Patients who received prior therapy with Vascular Endothelial Growth Factor (VEGF) pathway inhibitor within 4 weeks prior to study entry
• Patients who entered peptide receptor radionuclide therapy (PRRT) within 3 months prior to study entry
• Patients who received CT, biotherapy or radiotherapy within 4 weeks prior to study entry
• Patients who have previously received systemic (mammalian target of rapamycin) mTOR inhibitors
• Patients with a known hypersensitivity to everolimus or other rapamycins or to its excipients
• Patients with uncontrolled central nervous system (CNS) metastases
• Patients receiving chronic systemic treatment with corticosteroids or another immunosuppressive agent
• Patients with a known history of HIV seropositivity
• Patients with autoimmune hepatitis
• Patients with an active, bleeding diathesis
• Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study
• Patients who have a history of another primary malignancy and off treatment ≤ 3 years, with the exception of non-melanoma skin cancer and carcinoma in situ of the uterine cervix

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (40)

Novartis Investigative Site

Bordeaux, France

Location

Novartis Investigative Site

Lyon, France

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Novartis Investigative Site

Marseille, France

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Novartis Investigative Site

Paris, France

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Novartis Investigative Site

Bad Berka, 99438, Germany

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Novartis Investigative Site

Bad Berka, Germany

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Novartis Investigative Site

Berlin, 13353, Germany

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Novartis Investigative Site

Berlin, Germany

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Novartis Investigative Site

Bonn, Germany

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Novartis Investigative Site

Frankfurt, Germany

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Novartis Investigative Site

Heidelberg, 69120, Germany

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Novartis Investigative Site

Heidelberg, Germany

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Novartis Investigative Site

Mainz, 55131, Germany

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Novartis Investigative Site

Mainz, Germany

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Novartis Investigative Site

Munich, Germany

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Novartis Investigative Site

Bologna, BO, 40138, Italy

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Novartis Investigative Site

Viagrande, CT, 95029, Italy

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Novartis Investigative Site

Milan, MI, 20141, Italy

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Novartis Investigative Site

Perugia, PG, 06129, Italy

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Novartis Investigative Site

Roma, RM, 00189, Italy

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Novartis Investigative Site

Bologna, Italy

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Novartis Investigative Site

Milan, Italy

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Novartis Investigative Site

Perugia, Italy

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Novartis Investigative Site

Roma, Italy

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Novartis Investigative Site

Viagrande, Italy

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Novartis Investigative Site

Rotterdam, Netherlands

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Novartis Investigative Site

Gdansk, 80-952, Poland

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Novartis Investigative Site

Gdansk, Poland

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Novartis Investigative Site

Warsaw, Poland

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Novartis Investigative Site

Barcelona, Catalonia, 08907, Spain

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Novartis Investigative Site

Barcelona, Catalonia, Spain

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Novartis Investigative Site

Barcelona, Spain

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Novartis Investigative Site

Madrid, Spain

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Novartis Investigative Site

Uppsala, Spain

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Novartis Investigative Site

Stockholm, Sweden

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Novartis Investigative Site

Uppsala, SE-751 85, Sweden

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Novartis Investigative Site

Glasgow, United Kingdom

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Novartis Investigative Site

Glasgow - Scotland, G12 OYN, United Kingdom

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Novartis Investigative Site

Manchester, M20 9BX, United Kingdom

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Novartis Investigative Site

Manchester, United Kingdom

Location

MeSH Terms

Conditions

Carcinoma; Carcinoid Tumor; Neuroendocrine Tumors

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Adenocarcinoma; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2008
• First Posted: June 3, 2008
• Study Start: June 24, 2009
• Primary Completion: November 7, 2016
• Study Completion: November 7, 2016
• Last Updated: January 25, 2019
• Results First Posted: January 25, 2019

Record last verified: 2018-08

Locations

FR (4); PL (3); ES (5); SE (2); NL (1); GB (4); IT (10); DE (11)