A Dose-finding Study of a Combination of Imatinib and BYL719 in the Treatment of 3rd Line GIST Patients

NCT ID: NCT01735968

Last Updated: 2020-12-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-02-27
• Study Completion Date: 2018-10-19

Brief Summary

The purpose of this study is to determine a maximum tolerated dose and/or recommended phase 2 dose of a combination of imatinib and BYL719 in the treatment of 3rd line GIST patients.

Conditions

3rd Line GIST

Keywords

Imatinib mesylate; STI571; BYL719; GIST; 3rd line GIST

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

STI571 (imatinib mesylate) and BYL719

The study will comprise of 2 parts. A dose escalation and a dose expansion part. All patients in the dose escalation part will have a pharmacokinetic (PK) run-in period of 7 days receiving imatinib monotherapy. Patients will receive increasing doses of BYL719 (200, 300, 400 mg) in combination with 400mg imatinib daily until maximum tolerated dose (MTD) and rapid phase 2 dose (RP2D) is determined. Approximately 35 patients will enter the expansion phase.

Group Type: EXPERIMENTAL

ST571 + BYL719

Intervention Type: DRUG

Evaluable patients must meet the minimum treatment and safety evaluation requirements of the study. Patients will be treated until they experience progression of disease, withdraw consent, or experience unacceptable toxicity. One study cycle equals 28 days.

Interventions

ST571 + BYL719

Evaluable patients must meet the minimum treatment and safety evaluation requirements of the study. Patients will be treated until they experience progression of disease, withdraw consent, or experience unacceptable toxicity. One study cycle equals 28 days.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male or female patients ≥ 18 years of age -WHO performance status (PS) of 0-2 -Histologically confirmed diagnosis of GIST that is unresectable or metastatic -.Available tissue specimen: • Dose-escalation part: patients must have available archival tumor tissue which can be shipped during the course of the study. In the absence of archival tumor tissue, patients must agree to a fresh pre-treatment biopsy at screening. • Dose-expansion part: patients must have available archival tumor tissue which can be shipped during the course of the study and must agree to a fresh pre-treatment biopsy
• Failed prior therapy with imatinib followed by sunitinib for the treatment of unresectable or metastatic GIST. Note the following specific criteria for the two parts of the trial: • Dose-escalation part: patients who failed prior therapy with imatinib and then have failed therapy with sunitinib. Treatment failure may be due to either disease progression on therapy (both imatinib and sunitinib) or intolerance to therapy (sunitinib) • Dose-escalation part patients may have had additional lines of therapy than imatinib and sunitinib dose-expansion part: patients must have documented disease progression on both imatinib and sunitinib. In addition, patients may have had no more than two lines of prior therapy (i.e. treatment with imatinib followed by treatment with sunitinib). • Note: Adjuvant imatinib will not count as a prior course of imatinib for the purposes of this criterion 6. Radiological (CT/MRI) confirmation of disease progression (RECIST criteria) during prior therapy with imatinib and sunitinib will be required for patients entering the Dose-expansion part

Exclusion Criteria

-Previous treatment with PI3K inhibitors -Patient has active uncontrolled or symptomatic central nervous system (CNS) metastases Note: A patient with controlled and asymptomatic CNS metastases may participate in this trial. As such, the patient must have completed any prior treatment for CNS metastases > 28 days (including radiotherapy and/or surgery) prior to start of treatment in this study and should not be receiving chronic corticosteroid therapy for the CNS metastases -Severe and/or uncontrolled concurrent medical condition that, in the opinion of the investigator, could cause unacceptable safety risks or compromise compliance with the protocol (e.g. acute or chronic liver, pancreatic disease, severe renal disease considered unrelated to study disease, chronic pulmonary disease including dyspnea at rest from any cause) -Patients with diabetes mellitus requiring insulin treatment and/or with clinical signs or with FPG >120mg/dL / 6.7mmol/L, or history of documented steroid-induced diabetes mellitus -Patient who has not recovered to grade 1 or better from any adverse events related to previous imatinib and/or sunitinib therapy before screening procedures are initiated

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Oregon Health and Science University Dept. of OHSU (3)

Portland, Oregon, United States

Novartis Investigative Site

Leuven, , Belgium

Novartis Investigative Site

Bordeaux, , France

Novartis Investigative Site

Berlin, , Germany

Novartis Investigative Site

Essen, , Germany

Novartis Investigative Site

Bologna, BO, Italy

Novartis Investigative Site

Candiolo, TO, Italy

Novartis Investigative Site

Groningen, , Netherlands

Novartis Investigative Site

Leiden, , Netherlands

Novartis Investigative Site

Barcelona, Catalonia, Spain

Novartis Investigative Site

Leeds, , United Kingdom

Countries

South Korea; United States; Belgium; France; Germany; Italy; Netherlands; Spain; United Kingdom

References

Pantaleo MA, Heinrich MC, Italiano A, Valverde C, Schoffski P, Grignani G, Reyners AKL, Bauer S, Reichardt P, Stark D, Berhanu G, Brandt U, Stefanelli T, Gelderblom H. A multicenter, dose-finding, phase 1b study of imatinib in combination with alpelisib as third-line treatment in patients with advanced gastrointestinal stromal tumor. BMC Cancer. 2022 May 6;22(1):511. doi: 10.1186/s12885-022-09610-4.

Reference Type: DERIVED

PMID: 35524239 (View on PubMed)

Related Links

https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17545

Results for CSTI571X2103 can be found on the Novartis Clinical Trial Results Website

Other Identifiers

2012-003273-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CSTI571X2103

Identifier Type: -

Identifier Source: org_study_id