Clinical trial NCT00688623: RAMSETE: RAD001 in Advanced and Metastatic Silent Neuro-endocrine Tumors in Europe
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
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2008-06-03
Enrollment: 73
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Percentage of Participants' Best Overall Response Rate at 12 Months - Per Protocol Set (PP)
timeFrame: baseline up to approximately 12 months
measure: Percentage of Participants With Objective Response Rate at 12 Months - Per Protocol Set (PP)
timeFrame: baseline up to approximately 12 months
measure: Percentage of Participants With a Overall Response Rate With a Complete Response (CR) or Partial Response (PR) at 12 Months ITT Set
timeFrame: baseline up to approximately 12 months
measure: Percentage of Participants With Objective Response Rate at 12 Months ITT Set
timeFrame: baseline up to approximately 12 months
Secondary outcomes:
measure: Percentage of Participants With Disease Control Rate (DCR) at 12 Months for Per Protocol (PP) and ITT Sets
timeFrame: baseline up to approximately 12 months
measure: Percentage of Participants' Biochemical Response Rate Based on the Tumor Marker Chromogranin A (CgA)
timeFrame: baseline up to approximately 12 months
measure: Duration of Progression Free Survival (PFS) for Per Protocol (PP) and ITT Sets
timeFrame: baseline up to approximately 12 months
measure: Overall Survival (OS) for Per Protocol (PP) and ITT Sets
timeFrame: baseline up to approximately 15 months
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Novartis Investigative Site
city: Lyon
country: France
facility: Novartis Investigative Site
city: Marseille
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Bad Berka
country: Germany
facility: Novartis Investigative Site
city: Bad Berka
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Bonn
country: Germany
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Heidelberg
country: Germany
facility: Novartis Investigative Site
city: Heidelberg
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
city: Munich
country: Germany
facility: Novartis Investigative Site
city: Bologna
country: Italy
facility: Novartis Investigative Site
state: BO
city: Viagrande
country: Italy
facility: Novartis Investigative Site
state: CT
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Perugia
country: Italy
facility: Novartis Investigative Site
state: PG
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Bologna
country: Italy
facility: Novartis Investigative Site
city: Milano
country: Italy
facility: Novartis Investigative Site
city: Perugia
country: Italy
facility: Novartis Investigative Site
city: Roma
country: Italy
facility: Novartis Investigative Site
city: Viagrande
country: Italy
facility: Novartis Investigative Site
city: Rotterdam
country: Netherlands
facility: Novartis Investigative Site
city: Gdansk
country: Poland
facility: Novartis Investigative Site
city: Gdansk
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Cataluña
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Cataluña
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Uppsala
country: Spain
facility: Novartis Investigative Site
city: Stockholm
country: Sweden
facility: Novartis Investigative Site
city: Uppsala
country: Sweden
facility: Novartis Investigative Site
city: Glasgow - Scotland
country: United Kingdom
facility: Novartis Investigative Site
city: Glasgow
country: United Kingdom
facility: Novartis Investigative Site
city: Manchester
country: United Kingdom
facility: Novartis Investigative Site
city: Manchester
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: