Phase 2
N=42
Everolimus in Combination With Imatinib in Patients With Glivec Refractory/Resistant Gastrointestinal Stromal Tumors
Gastrointestinal Stromal Tumors
Bottom Line
View on ClinicalTrials.gov: NCT01275222 ↗Enrolled (actual)
42
Serious AEs
48.7%
Results posted
Jun 2021
Primary outcome: Primary: Number of Participants With Adverse Events (AEs): Phase I & II — 13; 13; 5; 11 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- RAD001 (Drug); Imatinib 600mg/day (Glevec is the brand name for imatinib) (Drug); Imatinib 800mg/day (Glevec is the brand name for imatinib) (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Novartis Pharmaceuticals
- Primary completion
- Sep 2008
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Adverse Events (AEs): Phase I & II |
13; 13; 5; 11; 27; 47 | — |
| PRIMARY Best Overall Response (BOR) as Assessed by Overall Response (Complete Response (CR) & Partial Response (PR)) - Phase I & II |
0; 1; 0; 0.0; 0; 1 | — |
| PRIMARY Trough Concentrations for RAD001 and for Imatinib - Phase II |
24.300; 12.100; 19.900; 12.750; 10.950; 7.840 | — |
| PRIMARY Overall Survival (OS) - Phase I & II |
9.4; 10.9; 18.7; NA; 14.9; 10.7 | — |
| PRIMARY 4-Month Progression-free Survival (PFS) Rate - Phase II |
17.4; 37.1 | — |
| PRIMARY Progression-free Survival (PFS) - Phase II |
1.9; 3.5 | — |
| SECONDARY 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. |
— | — |
| SECONDARY 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). |
— | — |
| SECONDARY 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. |
— | — |
Summary
This trial was a Phase I/II, non-randomized, open label, multi-center study, following a sequential 2-part design.
Eligibility Criteria
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.
Data sourced from ClinicalTrials.gov (NCT01275222). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.