Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01275222
First received: January 10, 2011
Last updated: February 9, 2013
Last verified: February 2013

January 10, 2011
February 9, 2013
November 2002
September 2008   (final data collection date for primary outcome measure)
  • 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). [ Designated as safety issue: No ]
  • assess the pharmacokinetics of the combination administration of RAD001 and imatinib in this patient population. [ Designated as safety issue: No ]
  • assess clinical efficacy of the combination regimen in this patient population. [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01275222 on ClinicalTrials.gov Archive Site
  • 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. [ Designated as safety issue: No ]
  • 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). [ Designated as safety issue: No ]
  • 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. [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Everolimus in Combination With Imatinib in Patients With Glivec Refractory/Resistant Gastrointestinal Stromal Tumors
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.

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).
Not Provided
Interventional
Phase 1
Phase 2
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Gastrointestinal Stromal Tumors
Drug: Everolimus + Imatinib
Experimental: RAD001 + Glivec
Intervention: Drug: Everolimus + Imatinib
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
120
September 2008
September 2008   (final data collection date for primary outcome measure)

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

Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Belgium,   France,   Germany
 
NCT01275222
CRAD001C2206
Not Provided
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
February 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP