Everolimus in Combination With Imatinib in Patients With Glivec Refractory/Resistant Gastrointestinal Stromal Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01275222
Recruitment Status : Completed
First Posted : January 12, 2011
Last Update Posted : June 18, 2018
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:

This trial was a Phase I/II, non-randomized, open label, multi-center study, following a sequential 2- part design. The first part, Phase I, was designed to assess whether there is a pharmacokinetic interaction between Glivec/Gleevec (imatinib) and RAD001(everolimus) as well as to collect safety data when these two drugs are co-administered. The second part, (Phase II), was designed to assess the potential efficacy of the combination in imatinib-resistant GIST patients in two strata of patients:

  • Patients resistant to imatinib as first-line drug therapy and in whom the maximum tolerated dose was at least 600 mg/d (Stratum 1, first-line resistant/refractory)
  • Patients resistant to imatinib as well as to post-imatinib drug therapy (Stratum 2, post second-line therapy).

Condition or disease Intervention/treatment Phase
Gastrointestinal Stromal Tumors Drug: Everolimus Drug: Imatinib Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 120 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I-II, Open-label Study of RAD001 in Combination With Glivec®/Gleevec™ (Imatinib) in Patients With Glivec/Gleevec-refractory/Resistant Gastrointestinal Stromal Tumors.
Study Start Date : November 2002
Actual Primary Completion Date : September 2008
Actual Study Completion Date : September 2008

Arm Intervention/treatment
Experimental: RAD001 + Glivec Drug: Everolimus
Other Name: RAD001

Drug: Imatinib
Glevec is the brand name for imatinib.
Other Name: STI571

Primary Outcome Measures :
  1. assess the safety and tolerability of the combination administration of RAD001 and imatinib when given to patients with imatinib-refractory gastro-intestinal stromal tumors (GIST).
  2. assess the pharmacokinetics of the combination administration of RAD001 and imatinib in this patient population.
  3. assess clinical efficacy of the combination regimen in this patient population.

Secondary Outcome Measures :
  1. assess mTOR pathway activity before treatment, and inhibition of mTOR pathway activity during treatment as a predictive factor of response, as shown by molecular pathological examination of the tumor.
  2. assess the relationship between drug-induced changes in the principal molecular marker of intratumoral mTOR activity and changes in other molecular markers of tumoral activity (e.g. indicators of pathway activity, cell proliferation and apoptosis).
  3. assess the relationship between drug-induced changes in tumoral metabolism, as shown by functional imaging with 18F-fluorodeoxyglucose positron emission tomography (FDC-PET), with clinical outcome and changes in molecular pathology.

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

Inclusion Criteria:

Phase l:

  • Patients aged ≥ 18 years
  • Patients with a histologically proven diagnosis of GIST and clinical evidence of resistance to imatinib despite at least 4 months continuous treatment with imatinib
  • Patients with at least 2 months at a dosage of ≥ 600 mg/day (progression despite uninterrupted therapy for 2 months at ≥800 mg/d for patients entering the Phase I cohort investigating the 800 mg/d dose)
  • Patients were to have at least one measurable lesion (longest diameter ≥20 mm on conventional CT or MRI scan
  • patients were to have ≥10 mm on spiral CT) and were to have a WHO Performance Status Score ≤ 2.
  • Patients also were to have adequate bone marrow, liver and renal function on imatinib treatment, as specified in the protocol

Phase ll:

• For Phase II (Stratum 2) patients must have progression on other 2nd line drug therapies following prior progression on imatinib (Stratum 2)

Exclusion Criteria:

  • Women who are pregnant or breast-feeding
  • Patients presenting with known or symptomatic CNS metastases or leptomeningeal involvement
  • 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 with 6 months, unstable angina, chronic or acute renal or liver disease, uncontrolled infections including abscess or fistulae, etc.)
  • 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
  • Patients unwilling to or unable to comply with the protocol
  • Patients who are receiving glucocorticoids (only if the p70s6 kinase1 assay is being performed), since these have been shown to inhibit p70s6 kinase1 activity.

Other protocol-defined inclusion/exclusion criteria may apply

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 identifier (NCT number): NCT01275222

United States, Massachusetts
Dana Faber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, New York
College of Physicians & Surgeons of Columbia University
New York, New York, United States, 10032
United States, Pennsylvania
Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111-2497
Novarts Investigative Site
Edegem, Belgium, 2650
Novarts Investigative Site
Leuven, Belgium, 3000
Novartis Investigative Site
Bordeaux Cedex, France, 33076
Novartis Investigative Site
Lille Cedex, France, 59020
Novartis Investigative Site
Lyon Cedex 08, France, 69373
Novartis Investigative Site
Marseille, France, 13005
Novartis Investigative Site
Villejuif, France, 94805
Novartis Investigative Site
Berlin, Germany, 13125
Novartis Investigative Site
Frankfurt, Germany, 60488
Novartis Investigative Site
Hamburg, Germany, 20246
Novartis Investigative Site
Koln, Germany, 50973
Novartis Investigative Site
Muenchen, Germany, 81377
Novartis Investigative Site
Tubingen, Germany, 72076
Sponsors and Collaborators
Novartis Pharmaceuticals
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

Responsible Party: Novartis Pharmaceuticals Identifier: NCT01275222     History of Changes
Other Study ID Numbers: CRAD001C2206
First Posted: January 12, 2011    Key Record Dates
Last Update Posted: June 18, 2018
Last Verified: June 2018

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Imatinib resistant
Imatinib-refractory/resistant gastrointestinal stromal tumors

Additional relevant MeSH terms:
Gastrointestinal Stromal Tumors
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Imatinib Mesylate
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action