Conditions: Gastrointestinal Stromal Tumors
Keywords: RAD001 everolimusGIST everolimus mTOR Imatinib resistant Imatinib-refractory/resistant gastrointestinal stromal tumors Gastrointestinal Stromal Tumors(GIST) soft tissue sarcoma stomach tumor tumor of interstitial cells of Cajal (ICC) digestive system cancer
Allocation: NON_RANDOMIZED | Intervention model: SEQUENTIAL
Enrollment: 117
Healthy volunteers: no

Brief summary:
This trial was a Phase I/II, non-randomized, open label, multi-center study, following a sequential 2-part design.

Detailed description:
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).

It was decided to discontinue the study and close to further enrollment based on alternative treatment options that became available. Phase 1 and Phase 2 Stratum 1 were ended early on 02-Nov-2006. Investigators were allowed to complete the enrollment in the Phase 2 Stratum 2.

Arms:
arm 1: RAD001 20 mg was given once a week. arm 2: RAD001 2.5 mg was given in combination with Glivec/Gleevec 600mg/day. arm 3: RAD001 5 mg was given in combination with Glivec/Gleevec 600mg/day. arm 4: RAD001 2.5 mg was given in combination with Glivec/Gleevec 800mg/day. arm 5: All first-line resistant/refractory patients received RAD001 2.5mg/day in combination with Glivec/Gleevec at a dose of 600mg/day. arm 6: All post-second-line patients received RAD001 2.5mg/day in combination with Glivec/Gleevec at a dose of 600mg/day

Interventions: intervention 1: RAD001 intervention 2: Imatinib 600mg/day (Glevec is the brand name for imatinib) intervention 3: Imatinib 800mg/day (Glevec is the brand name for imatinib)
Intervention descriptions: intervention 1: RAD001 was in tablets of 0.5 mg, 1.0 mg, 2.5 mg and 5.0 mg strength and was taken by mouth, once a week or once a day depending upon the treatment group the patient was enrolled into. intervention 2: Glivec/Gleevec was supplied as commercialized 100 mg and 400 mg tablets. Gleevec/Glivec was provided as capsules of 100 mg strength in bottles containing 60 capsules each. The use of this supply was study center specific. Glivec/Gleevec was taken, by mouth, at a dose of 300 mg twice a day. The Glivec/Gleevec regimen was changed from 600 mg once a day to 300 mg BID, by an amendment since taking too many tablets at once was difficult for patients with gastro-intestinal disease. In the phase II part of the study all patients received Glivec 600 mg/day. intervention 3: Glivec/Gleevec was supplied as commercialized 100 mg and 400 mg tablets. Gleevec/Glivec was provided as capsules of 100 mg strength in bottles containing 60 capsules each. The use of this supply was study center specific. Glivec/Gleevec was taken, by mouth. In the phase II part of the study all patients received Glivec 600 mg/day, except for 2 patients who received Glivec at a dose of 800 mg/day. This dose was permitted in Phase II as it was found to be safe in Phase I.

Protocol document: