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

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ClinicalTrials.gov Identifier: NCT01735968
Recruitment Status : Completed
First Posted : November 28, 2012
Last Update Posted : December 21, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE November 15, 2012
First Posted Date  ICMJE November 28, 2012
Last Update Posted Date December 21, 2020
Actual Study Start Date  ICMJE February 27, 2013
Actual Primary Completion Date October 19, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 21, 2012)
  • Frequency of dose limiting toxicities (DLTs) [ Time Frame: 28 days (1st cycle) ]
    Dose limiting toxicity (DLT) will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) (v4.0.3), unless otherwise specified in the protocol.
  • Characteristics of dose limiting toxicities (DLTs) [ Time Frame: 28 days (1st cycle) ]
    Dose limiting toxicity (DLT) will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) (v4.0.3), unless otherwise specified in the protocol.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 21, 2012)
  • Frequency and characteristics of DLTs [ Time Frame: 28 days (1st cycle) ]
    Dose limiting toxicity (DLT) will be assessed using CTCAE (v4.0.3), unless otherwise specified in the protocol.
  • Imatinib and BYL719 plasma concentrations vs time profile [ Time Frame: 28 days (1st cycle) ]
  • Clinical benefit rate (CBR) [ Time Frame: 28 days (1st cycle) ]
    Clinical benefit rate is defined as the rate of confirmed complete response (CR) or partial response (PR), or stable disease (SD) which lasts for at least 16 weeks.Tumor response will be determined locally by the investigator sites according to Novartis guideline on the Response Evaluation Criteria in Solid Tumors, based on RECIST Version 1.1.
  • Type of adverse drug reactions [ Time Frame: 28 days (1st cycle) ]
  • Frequency of adverse drug reactions [ Time Frame: 28 days (1st cycle) ]
  • Severity of adverse drug reactions [ Time Frame: 28 days (1st cycle) ]
  • Effect of basic Pharmacokinetics (PK) parameter: AUC0-24 [ Time Frame: 28 days (1st cycle) ]
  • Effect of basic PK parameter: Cmax [ Time Frame: 28 days (1st cycle) ]
  • Effect of basic PK parameter: Tmax [ Time Frame: 28 days (1st cycle) ]
  • Effect of basic PK parameter: CL/F [ Time Frame: 28 days (1st cycle) ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Dose-finding Study of a Combination of Imatinib and BYL719 in the Treatment of 3rd Line GIST Patients
Official Title  ICMJE A Dose-finding Phase Ib Multicenter Study of Imatinib in Combination With the Oral Phosphatidyl-inositol 3-kinase (PI3K) Inhibitor BYL719 in Patients With Gastrointestinal Stromal Tumor (GIST) Who Failed Prior Therapy With Imatinib and Sunitinib
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE 3rd Line GIST
Intervention  ICMJE Drug: 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.
Study Arms  ICMJE Experimental: 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.
Intervention: Drug: ST571 + BYL719
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 2, 2016)
56
Original Estimated Enrollment  ICMJE
 (submitted: November 21, 2012)
50
Actual Study Completion Date  ICMJE October 19, 2018
Actual Primary Completion Date October 19, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   France,   Germany,   Italy,   Netherlands,   Spain,   United Kingdom,   United States
Removed Location Countries Korea, Republic of
 
Administrative Information
NCT Number  ICMJE NCT01735968
Other Study ID Numbers  ICMJE CSTI571X2103
2012-003273-25 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP