Gastrointestinal Stromal TumorsPhase 1/2NCT01275222
Everolimus in Combination With Imatinib in Patients With Glivec Refractory/Resistant Gastrointestinal Stromal Tumors
A Phase 1/2 study testing RAD001, Imatinib 600mg/day (Glevec is the brand name for imatinib) and Imatinib 800mg/day (Glevec is the brand name for imatinib) in people with Gastrointestinal Stromal Tumors, run by Novartis Pharmaceuticals at 16 sites in 4 countries.
Trial summary
This trial was a Phase I/II, non-randomized, open label, multi-center study, following a sequential 2-part design. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastrointestinal Stromal Tumors
- What is being tested?
- RAD001, Imatinib 600mg/day (Glevec is the brand name for imatinib) and Imatinib 800mg/day (Glevec is the brand name for imatinib)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 117 participants
- Where
- 16 sitesin 4 countries
- Study dates
- 13 Nov 2002to 3 Sep 2008
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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)
Who cannot join
- 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.
Trial locations and contacts
16 sites in 4 countries.
16 sites in 4 countries
Germany6 sites
Novartis Investigative Site
Berlin, 13125
Novartis Investigative Site
Cologne, 50937
Novartis Investigative Site
Frankfurt, 60488
Novartis Investigative Site
Hamburg, 20246
Novartis Investigative Site
München, 81377
Novartis Investigative Site
Tübingen, 72076
France5 sites
Novartis Investigative Site
Bordeaux, 33076
Novartis Investigative Site
Lille, 59020
Novartis Investigative Site
Lyon, F-69373
Novartis Investigative Site
Marseille, 13385
Novartis Investigative Site
Villejuif, 94805
United States3 sites
Dana Farber Cancer Institute Dept of Sarcoma Oncology
Boston, Massachusetts, 02215
College of Physicians and Surgeons of Columbia University
New York, New York, 10032
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
Belgium2 sites
Novartis Investigative Site
Edegem, Antwerpen, 2650
Novartis Investigative Site
Leuven, 3000
About this study
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.
This trial was a Phase I/II, non-randomized, open label, multi-center study, following a sequential 2-part design.
Read the 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.
- Conditions
- Gastrointestinal Stromal Tumors
- Being tested
- RAD001, Imatinib 600mg/day (Glevec is the brand name for imatinib), Imatinib 800mg/day (Glevec is the brand name for imatinib)
- 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
- Medical subject headings
- Gastrointestinal Stromal Tumors, Sarcoma, Stomach Neoplasms, Digestive System Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RAD001Drug
Also called everolimus
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.
Imatinib 600mg/day (Glevec is the brand name for imatinib)Drug
Also called STI571
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.
Imatinib 800mg/day (Glevec is the brand name for imatinib)Drug
Also called STI571
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.
| Study group | Role | What they receive |
|---|---|---|
| Phase l: RAD001 20mg/week | Experimental | RAD001 20 mg was given once a week. Receives: Drug: RAD001 |
| Phase l: RAD001 2.5mg/day + Glivec 600mg/day | Experimental | RAD001 2.5 mg was given in combination with Glivec/Gleevec 600mg/day. Receives: Drug: RAD001; Drug: Imatinib 600mg/day (Glevec is the brand name for imatinib) |
| Phase l: RAD001 5mg/day + Glivec 600mg/day | Experimental | RAD001 5 mg was given in combination with Glivec/Gleevec 600mg/day. Receives: Drug: RAD001; Drug: Imatinib 600mg/day (Glevec is the brand name for imatinib) |
| Phase l: RAD001 2.5mg/day + Glivec 800mg/day | Experimental | RAD001 2.5 mg was given in combination with Glivec/Gleevec 800mg/day. Receives: Drug: RAD001; Drug: Imatinib 600mg/day (Glevec is the brand name for imatinib) |
| Phase ll - Stratum l (first-line resistant/refractory): RAD001 2.5mg/day + Glivec 600mg/day | Experimental | All first-line resistant/refractory patients received RAD001 2.5mg/day in combination with Glivec/Gleevec at a dose of 600mg/day. Receives: Drug: RAD001; Drug: Imatinib 800mg/day (Glevec is the brand name for imatinib) |
| Phase ll - Stratum ll: (post second-line therapy): RAD001 2.5mg/day + Glivec 600mg/day | Experimental | All post-second-line patients received RAD001 2.5mg/day in combination with Glivec/Gleevec at a dose of 600mg/day Receives: Drug: RAD001; Drug: Imatinib 800mg/day (Glevec is the brand name for imatinib) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events (AEs): Phase I & II
Assessed safety and tolerability of the combination administration of RAD001 and imatinib when given to patients with imatinib-refractory gastro-intestinal stromal tumors (GIST) by number of participants with adverse events.
Measured: 4 - 8 weeks
Best Overall Response (BOR) as Assessed by Overall Response (Complete Response (CR) & Partial Response (PR)) - Phase I & II
Assessed clinical efficacy of the combination regimen in this patient population per BOR by Overall response (CR + PR). Complete response: Disappearance of all target lesions; Partial response: ≥ 30% decrease in the sum of the longest diameter of target lesions compared to baseline (and not ≥20% increase compared to smallest sum).
Measured: 6 - 8 weeks
Trough Concentrations for RAD001 and for Imatinib - Phase II
Assessed the pharmacokinetics (PK) of the combination administration of RAD001 and imatinib in this patient population.
Measured: Part II Daily regimen: Baseline, Days 8, 15 and thereafter approximately every two months starting at month 3 whenever possible
Overall Survival (OS) - Phase I & II
Assessed clinical efficacy of the combination regimen in this patient population per Overall Survival (OS). Overall survival was defined as the time from date of start of treatment to date of death due to any cause. For patients still receiving study medication at the time of the analysis, survival was censored at the date of last examination. If a patient was not known to have died but was no longer continuing with study medication, survival was censored at the date of last contact.
Measured: about 60 months
4-Month Progression-free Survival (PFS) Rate - Phase II
Assessed clinical efficacy of the combination regimen in this patient population per Progression-free survival (PFS). Progression-free survival (PFS) was the time from date of start of treatment to the date of first documented progression or death due to any cause. Per protocol (PP) population includes patients with no known overall lesion response during 4 months +/- 2 weeks, or who later had response of CR/PR/stable disease (SD). PP population excludes patients with no known response during 4 months + / -2 weeks and no subsequent CR/PR/SD.
Measured: about 4 months
Progression-free Survival (PFS) - Phase II
Assessed clinical efficacy of the combination regimen in this patient population per Progression-free survival (PFS). Progression-free survival (PFS) was the time from date of start of treatment to the date of first documented progression or death due to any cause. If a patient had not progressed or died, progression-free survival was censored at the time of last adequate tumor assessment.
According to the study protocol no tumor assessments were performed after discontinuation of treatment with study drug. Therefore, for all patients who discontinued treatment without a documented progression but died thereafter, death was considered as PFS event only if it occurred within the regular safety follow-up of 28 days after discontinuation. Otherwise, the PFS time was censored at the last adequate tumor assessment.
Measured: about 60 months
Secondary outcomes (3)
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 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.
Measured: about 60 months
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 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).
Measured: about 60 months
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.
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.
Measured: about 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2011 (estimated)
- Study start13 Nov 2002
- Primary completion3 Sep 2008
- Study completion3 Sep 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Gastrointestinal Stromal TumorsStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 117 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01275222
- Sponsor's protocol ID
- CRAD001C2206
- Status last verified
- Jun 2021
- First submitted
- 10 Jan 2011
- Last updated
- 25 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the triasl in line with applicable laws and regulations. This trial data will be available according to the process described on www.clinicalstudydatarequest.com.
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01275222
- Acronym / sponsor ID
- CRAD001C2206
- Conditions
- Gastrointestinal Stromal Tumors
- Keywords
- RAD001, everolimusGIST, everolimus, mTOR, Imatinib resistant, Imatinib-refractory/resistant, gastrointestinal stromal tumors, Gastrointestinal Stromal Tumors(GIST)
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 117 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 13 Nov 2002 (actual)
- Primary completion
- 3 Sep 2008 (actual)
- Study completion
- 3 Sep 2008 (actual)
- First posted
- 12 Jan 2011 (estimated)
- Results
- Posted 25 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Phase l: RAD001 20mg/week | Experimental | Drug: RAD001RAD001 20 mg was given once a week. |
| Phase l: RAD001 2.5mg/day + Glivec 600mg/day | Experimental | Drug: RAD001, Drug: Imatinib 600mg/day (Glevec is the brand name for imatinib)RAD001 2.5 mg was given in combination with Glivec/Gleevec 600mg/day. |
| Phase l: RAD001 5mg/day + Glivec 600mg/day | Experimental | Drug: RAD001, Drug: Imatinib 600mg/day (Glevec is the brand name for imatinib)RAD001 5 mg was given in combination with Glivec/Gleevec 600mg/day. |
| Phase l: RAD001 2.5mg/day + Glivec 800mg/day | Experimental | Drug: RAD001, Drug: Imatinib 600mg/day (Glevec is the brand name for imatinib)RAD001 2.5 mg was given in combination with Glivec/Gleevec 800mg/day. |
| Phase ll - Stratum l (first-line resistant/refractory): RAD001 2.5mg/day + Glivec 600mg/day | Experimental | Drug: RAD001, Drug: Imatinib 800mg/day (Glevec is the brand name for imatinib)All first-line resistant/refractory patients received RAD001 2.5mg/day in combination with Glivec/Gleevec at a dose of 600mg/day. |
| Phase ll - Stratum ll: (post second-line therapy): RAD001 2.5mg/day + Glivec 600mg/day | Experimental | Drug: RAD001, Drug: Imatinib 800mg/day (Glevec is the brand name for imatinib)All post-second-line patients received RAD001 2.5mg/day in combination with Glivec/Gleevec at a dose of 600mg/day |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RAD001Also: everolimusRAD001 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. | Drug | Phase l: RAD001 2.5mg/day + Glivec 600mg/day, Phase l: RAD001 2.5mg/day + Glivec 800mg/day, Phase l: RAD001 20mg/week, Phase l: RAD001 5mg/day + Glivec 600mg/day, Phase ll - Stratum l (first-line resistant/refractory): RAD001 2.5mg/day + Glivec 600mg/day, Phase ll - Stratum ll: (post second-line therapy): RAD001 2.5mg/day + Glivec 600mg/day |
| Imatinib 600mg/day (Glevec is the brand name for imatinib)Also: STI571Glivec/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. | Drug | Phase l: RAD001 2.5mg/day + Glivec 600mg/day, Phase l: RAD001 2.5mg/day + Glivec 800mg/day, Phase l: RAD001 5mg/day + Glivec 600mg/day |
| Imatinib 800mg/day (Glevec is the brand name for imatinib)Also: STI571Glivec/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. | Drug | Phase ll - Stratum l (first-line resistant/refractory): RAD001 2.5mg/day + Glivec 600mg/day, Phase ll - Stratum ll: (post second-line therapy): RAD001 2.5mg/day + Glivec 600mg/day |
Primary outcome
Number of Participants With Adverse Events (AEs): Phase I & II
Time frame: 4 - 8 weeks
Assessed safety and tolerability of the combination administration of RAD001 and imatinib when given to patients with imatinib-refractory gastro-intestinal stromal tumors (GIST) by number of participants with adverse events.
Best Overall Response (BOR) as Assessed by Overall Response (Complete Response (CR) & Partial Response (PR)) - Phase I & II
Time frame: 6 - 8 weeks
Assessed clinical efficacy of the combination regimen in this patient population per BOR by Overall response (CR + PR). Complete response: Disappearance of all target lesions; Partial response: ≥ 30% decrease in the sum of the longest diameter of target lesions compared to baseline (and not ≥20% increase compared to smallest sum).
Trough Concentrations for RAD001 and for Imatinib - Phase II
Time frame: Part II Daily regimen: Baseline, Days 8, 15 and thereafter approximately every two months starting at month 3 whenever possible
Assessed the pharmacokinetics (PK) of the combination administration of RAD001 and imatinib in this patient population.
Overall Survival (OS) - Phase I & II
Time frame: about 60 months
Assessed clinical efficacy of the combination regimen in this patient population per Overall Survival (OS). Overall survival was defined as the time from date of start of treatment to date of death due to any cause. For patients still receiving study medication at the time of the analysis, survival was censored at the date of last examination. If a patient was not known to have died but was no longer continuing with study medication, survival was censored at the date of last contact.
4-Month Progression-free Survival (PFS) Rate - Phase II
Time frame: about 4 months
Assessed clinical efficacy of the combination regimen in this patient population per Progression-free survival (PFS). Progression-free survival (PFS) was the time from date of start of treatment to the date of first documented progression or death due to any cause. Per protocol (PP) population includes patients with no known overall lesion response during 4 months +/- 2 weeks, or who later had response of CR/PR/stable disease (SD). PP population excludes patients with no known response during 4 months + / -2 weeks and no subsequent CR/PR/SD.
Progression-free Survival (PFS) - Phase II
Time frame: about 60 months
Assessed clinical efficacy of the combination regimen in this patient population per Progression-free survival (PFS). Progression-free survival (PFS) was the time from date of start of treatment to the date of first documented progression or death due to any cause. If a patient had not progressed or died, progression-free survival was censored at the time of last adequate tumor assessment. According to the study protocol no tumor assessments were performed after discontinuation of treatment with study drug. Therefore, for all patients who discontinued treatment without a documented progression but died thereafter, death was considered as PFS event only if it occurred within the regular safety follow-up of 28 days after discontinuation. Otherwise, the PFS time was censored at the last adequate tumor assessment.
3 secondary outcomes
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.
Time frame: about 60 months
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).
Time frame: about 60 months
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.
Time frame: about 60 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the triasl in line with applicable laws and regulations. This trial data will be available according to the process described on www.clinicalstudydatarequest.com.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
16 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing RAD001, Imatinib 600mg/day (Glevec is the brand name for imatinib) and Imatinib 800mg/day (Glevec is the brand name for imatinib) in people with Gastrointestinal Stromal Tumors, run by Novartis Pharmaceuticals at 16 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in Germany, France, United States, Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Adverse Events (AEs): Phase I & II (time frame: 4 - 8 weeks). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2021.