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

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ClinicalTrials.gov Identifier: NCT00688623
Recruitment Status : Completed
First Posted : June 3, 2008
Results First Posted : January 25, 2019
Last Update Posted : January 25, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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.

Condition or disease Intervention/treatment Phase
Advanced and Metastatic Silent Neuro-Endocrine Tumors Carcinoma Neuroendocrine Non Functioning Neuroendocrine Tumors (NETs) Non Syndromic Neuroendocrine Tumors Carcinoids Non Functioning Drug: Everolimus Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 73 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 24, 2009
Actual Primary Completion Date : November 7, 2016
Actual Study Completion Date : November 7, 2016


Arm Intervention/treatment
Experimental: Everolimus
Everolimus
Drug: Everolimus
Everolimus 5 mg tablets were supplied in blister packs




Primary Outcome Measures :
  1. Percentage of Participants' Best Overall Response Rate at 12 Months - Per Protocol Set (PP) [ Time Frame: baseline up to approximately 12 months ]
    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.

  2. Percentage of Participants With Objective Response Rate at 12 Months - Per Protocol Set (PP) [ Time Frame: baseline up to approximately 12 months ]
    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

  3. Percentage of Participants With a Overall Response Rate With a Complete Response (CR) or Partial Response (PR) at 12 Months ITT Set [ Time Frame: baseline up to approximately 12 months ]

    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.


  4. Percentage of Participants With Objective Response Rate at 12 Months ITT Set [ Time Frame: baseline up to approximately 12 months ]
    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 :
  1. Percentage of Participants With Disease Control Rate (DCR) at 12 Months for Per Protocol (PP) and ITT Sets [ Time Frame: baseline up to approximately 12 months ]
    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

  2. Percentage of Participants' Biochemical Response Rate Based on the Tumor Marker Chromogranin A (CgA) [ Time Frame: baseline up to approximately 12 months ]
    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.

  3. Duration of Progression Free Survival (PFS) for Per Protocol (PP) and ITT Sets [ Time Frame: baseline up to approximately 12 months ]
    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.

  4. Overall Survival (OS) for Per Protocol (PP) and ITT Sets [ Time Frame: baseline up to approximately 15 months ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. ≥ 18 years old
  2. Patients with advanced (unresectable or metastatic) biopsy proven non-syndromic neuro-endocrine carcinoma, low or intermediate grade
  3. 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
  4. Patients may have received previous treatments (chemotherapy, biotherapy, peptide-receptor radionuclide therapy); an overall maximum of 3 systemic treatment is allowed
  5. Patients with at least one measurable lesion
  6. Patients with an ECOG (Eastern Cooperative Oncology Group) Performance Status 0-2
  7. Adequate bone marrow function
  8. Adequate liver function
  9. Adequate renal function
  10. Adequate lipid profile

Exclusion criteria:

  1. Patients with poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, goblet cell carcinoid and small cell carcinoma
  2. Patients with carcinoid with hormone related symptoms (diarrhea ≥ 4 stools per day and/or flushes)
  3. Patients with Islet cell carcinomas or pancreatic NET
  4. Patients who received prior therapy with Vascular Endothelial Growth Factor (VEGF) pathway inhibitor within 4 weeks prior to study entry
  5. Patients who entered peptide receptor radionuclide therapy (PRRT) within 3 months prior to study entry
  6. Patients who received CT, biotherapy or radiotherapy within 4 weeks prior to study entry
  7. Patients who have previously received systemic (mammalian target of rapamycin) mTOR inhibitors
  8. Patients with a known hypersensitivity to everolimus or other rapamycins or to its excipients
  9. Patients with uncontrolled central nervous system (CNS) metastases
  10. Patients receiving chronic systemic treatment with corticosteroids or another immunosuppressive agent
  11. Patients with a known history of HIV seropositivity
  12. Patients with autoimmune hepatitis
  13. Patients with an active, bleeding diathesis
  14. Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study
  15. 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
  16. Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods
  17. Patients who are using other investigational agents or who had received investigational drugs ≤ 4 weeks prior to study treatment start
  18. Patients unwilling to or unable to comply with the protocol

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00688623


  Show 40 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00688623     History of Changes
Other Study ID Numbers: CRAD001CDE16
First Posted: June 3, 2008    Key Record Dates
Results First Posted: January 25, 2019
Last Update Posted: January 25, 2019
Last Verified: August 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Neuroendocrine tumors
non functioning neuroendocrine tumors
Non syndromic neuroendocrine tumors
non-functioning neuroendocrine tumors carcinoids
carcinoids
non-functioning carcinoids
adults
everolimus
NET
RAMSETE
CRAD001
Additional relevant MeSH terms:
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Neuroendocrine Tumors
Carcinoid Tumor
Endocrine Gland Neoplasms
Neoplasms
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Neoplasms, Glandular and Epithelial
Neoplasms by Site
Adenocarcinoma
Carcinoma
Endocrine System Diseases
Sirolimus
Everolimus
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents