Treatment of Patients With Everolimus and Imatinib Mesylate Who Have Progressive Gastro Intestinal Stromal Tumors (GIST) and Are Resistant to Imatinib Mesylate (Radix)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00510354
First received: July 31, 2007
Last updated: February 6, 2014
Last verified: February 2014
  Purpose

The purpose of this multicenter, single-arm, Simon two-stage, phase II trial is to determine the efficacy and safety of everolimus in combination with Imatinib mesylate in patients with previously treated, histologically proven GIST whose disease has recurred or progressed while receiving 400 mg/day of Imatinib mesylate at any time during at least a 2 months' treatment period.


Condition Intervention Phase
Progressive Gastrointestinal Stromal Tumor
Drug: Imatinib mesylate
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Multicenter, Single-arm, Two Stage Phase II Trial of RAD001 (Everolimus) With Imatinib in Imatinib-resistant Patients With Progressive GIST

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Tumor assessments should be performed by a CT or MRI scan after 4 months. Response to treatment with RAD001 plus Imatinib mesylate at 4 months (defined as progression-free survival (PFS) at 4 months). [ Time Frame: at 4 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Tolerability and safety assessed by AEs and SAEs. Objective tumor response rate (complete response [CR] and partial response [PR]) assessed by CT or MRI PFS at month 12 for patients with data available from follow up observation (optional) [ Time Frame: At 12 months ] [ Designated as safety issue: Yes ]

Enrollment: 27
Study Start Date: October 2006
Study Completion Date: November 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: RAD001 + Imatinib Drug: Imatinib mesylate

  Eligibility

Ages Eligible for Study:   30 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. Histological proven diagnosis of GIST
  2. Objectively documented evidence of progressive disease according to the RECIST criteria despite at least 2 months' continuous treatment with Imatinib mesylate at a dosage of 400 mg/day
  3. Clinical evidence of resistance to Imatinib mesylate on treatment with 400 mg/day Imatinib
  4. Progression must be documented on CT or MRI scans. The scans on which progression is documented should be at maximum 2 weeks old. New scans are only required as baseline scans if they are older then approx. 2 weeks
  5. At least one measurable lesion (longest diameter ≥ 20 mm on conventional CT or MRI scan; ≥ 10 mm on spiral CT)
  6. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
  7. Adequate bone marrow, liver and renal function on Imatinib treatment
  8. Patients must be at least 4 weeks since prior major surgery and recovered, at least 2 weeks since prior minor surgery and recovered

Exclusion criteria:

  1. Female patients who are pregnant or breast feeding, or patients of reproductive potential not employing an effective method of birth control. Because oral, implantable or injectable contraceptives may be affected by cytochrome P450 interactions, an appropriate method of birth control should be used throughout the trial in both sexes. Women of childbearing potential must have a negative serum pregnancy test ≤ 48 hours prior to the administration of study medication
  2. Patients presenting with known or symptomatic CNS metastases or leptomeningeal involvement
  3. Use of other investigational cancer therapies within 28 days prior to enrollment or which are currently being or planned to be received during the course of the study
  4. Patients who previously received rapamycin in combination with Imatinib
  5. Patients with any concurrent major medical condition liable to compromise the patient's participation in the study (e.g. known HIV infection, uncontrolled diabetes, serious cardiac dysrhythmia or condition, New York Heart Association classification of III or IV, congestive cardiac failure, myocardial infarction within 6 months, unstable angina, chronic or acute renal or liver disease, uncontrolled infections including abscess or fistulae, etc.)
  6. Patients with a history of another malignancy within 5 years prior to study entry, except curatively treated non-melanotic skin cancer or in-situ cervical cancer
  7. Patients receiving glucocorticoids (only if the p70s6 kinase-1 assay is being performed), since glucocorticoids have been shown to inhibit p70s6 kinase-1 activity

Other protocol defined inclusion/ exclusion criteria may apply

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00510354

Locations
Germany
Novartis Investigative Site
Berlin, Germany, 13125
Novartis Investigative Site
Essen, Germany, 45122
Novartis Investigative Site
Frankfurt, Germany, 60488
Novartis Investigative Site
Frankfurt/M, Germany, 60590
Novartis Investigative Site
Hannover, Germany, 30625
Novartis Investigative Site
Mannheim, Germany, 68167
Novartis Investigative Site
Tübingen, Germany, 72076
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00510354     History of Changes
Other Study ID Numbers: CRAD001C2454, 2005-004837-16
Study First Received: July 31, 2007
Last Updated: February 6, 2014
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Novartis:
Progressive GIST
Resistance to Imatinib mesylate

Additional relevant MeSH terms:
Gastrointestinal Stromal Tumors
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Imatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 30, 2014