Clinical Trial: Everolimus in Combination With Imatinib in Patients With Glivec Refractory/Resistant Gastrointestinal Stromal Tumors
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
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
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).
Detailed Summary:
Sponsor: Novartis Pharmaceuticals
Current Primary Outcome:
- 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).
- assess the pharmacokinetics of the combination administration of RAD001 and imatinib in this patient population.
- assess clinical efficacy of the combination regimen in this patient population.
Original Primary Outcome: Same as current
Current Secondary Outcome:
- 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.
- 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).
- 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.
Original Secondary Outcome: Same as current
Information By: Novartis
Dates:
Date Received: January 10, 2011
Date Started: November 2002
Date Completion:
Last Updated: August 4, 2016
Last Verified: August 2016