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RAMSETE: RAD001 in Advanced and Metastatic Silent Neuro-endocrine Tumors in Europe (RAMSETE/CDE16)

Primary Purpose

Advanced and Metastatic Silent Neuro-Endocrine Tumors, Carcinoma, Neuroendocrine

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Everolimus

About this trial

This is an interventional treatment trial for Advanced and Metastatic Silent Neuro-Endocrine Tumors focused on measuring Neuroendocrine tumors, non functioning neuroendocrine tumors, Non syndromic neuroendocrine tumors, carcinoids, non-functioning carcinoids, adults, everolimus, NET, RAMSETE, CRAD001, non-functioning neuroendocrine tumors carcinoids

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

≥ 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

Exclusion criteria:

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
Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods
Patients who are using other investigational agents or who had received investigational drugs ≤ 4 weeks prior to study treatment start
Patients unwilling to or unable to comply with the protocol

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Everolimus

Arm Description

Everolimus

Outcomes

Primary Outcome Measures

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.

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

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.

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.

Secondary Outcome Measures

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

DCR was based on central radiologic review and is defined as the percentage of patients with a best overall response of 'Complete response' (CR), 'Partial response' (PR) or 'Stable disease' (SD). Relative frequencies together with their exact 2-sided 80% confidence intervals were presented

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

Biochemical response was defined as level and change from baseline in CgA during the course of the trial. The resulting values showed a high variation and were not interpretable, as different methodology was used for the assessment of CgA at the individual centers.

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

Duration of PFS was defined as the time from first study drug administration to objective tumor progression or death from any cause. Observations from patients not experiencing tumor progression or death at date of database closure were censored with the date of their last adequate tumor assessment. Progression was either 1) a 20% increase in the sum of the longest diameter of all target lesions, taking as reference the smallest sum of longest diameter of all target lesions recorded at or after baseline or 2) the appearance of a new lesion or 3) the unequivocal progression of non-target lesions.

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

OS was defined as the time from first study drug administration to death from any cause. If a patient was not known to have died at date of database closure, overall survival was censored at the date of last contact.

Full Information

NCT ID

NCT00688623

First Posted

May 30, 2008

Last Updated

August 14, 2018

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT00688623

Brief Title

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

Acronym

RAMSETE/CDE16

Official Title

A Single Arm, Multicenter Single Stage Phase II Trial of RAD001 as Monotherapy in the Treatment of Metastatic Non Syndromic Neuro-endocrine Tumors

Study Type

Interventional

2. Study Status

Record Verification Date

August 2018

Overall Recruitment Status

Completed

Study Start Date

June 24, 2009 (Actual)

Primary Completion Date

November 7, 2016 (Actual)

Study Completion Date

November 7, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

73 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Everolimus

Arm Type

Experimental

Arm Description

Everolimus

Intervention Type

Drug

Intervention Name(s)

Everolimus

Intervention Description

Everolimus 5 mg tablets were supplied in blister packs

Primary Outcome Measure Information:

Title

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

Description

Time Frame