BGJ398 in Combination With Imatinib Mesylate in Patients With Untreated Advanced Gastrointestinal Stromal Tumor (GIST)
A Phase Ib/II Study of BGJ398 in Combination With Imatinib Mesylate in Patients With Untreated Advanced Gastrointestinal Stromal Tumor (GIST)
1 other identifier
interventional
16
1 country
7
Brief Summary
The goal of a phase Ib clinical trial is to find the doses of drugs that are safe. Although BGJ398 has been given to patients safely on its own, it has never been given together with imatinib mesylate. In this study, we will test the safety of taking BGJ398 with imatinib mesylate. The investigators will learn this by closely checking for side effects that the patient may experience. Side effects can be seen in laboratory studies, on physical examination, or by asking the patient.Once a dose has been determined to be safe, a larger Phase II study will be done in patients with advanced GIST who have never received any prior treatments.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Oct 2014
Longer than P75 for phase_1
7 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 2, 2014
CompletedStudy Start
First participant enrolled
October 2, 2014
CompletedFirst Posted
Study publicly available on registry
October 6, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 25, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
March 25, 2019
CompletedResults Posted
Study results publicly available
March 30, 2020
CompletedMarch 30, 2020
March 1, 2019
4.5 years
October 2, 2014
February 13, 2020
March 16, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Phase Ib Study: Number of Participants With Dose-Limiting Toxicities
The phase Ib will be pursued in standard 3+3 format, based on toxicities encountered during the first cycle of therapy.
1 year
Phase Ib Portion: Response Rate (RR)
(CR+PR, RECIST 1.1) and by CHOI criteria PHASE 1b PARTICIPANTS ONLY Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
32 weeks
Secondary Outcomes (1)
Phase Ib Study: Response Rate (RR)
32 weeks
Study Arms (1)
BGJ398 With Imatinib Mesylate
EXPERIMENTALBGJ398 With Imatinib Mesylate In the phase Ib portion of the study, patients will receive imatinib at 400 mg once daily and BGJ398 at the standard 3+3 escalation doses for 21 days on, 7 days off (treatment schedule A).Using treatment schedule A, if dose level 1 to -2 is identified as the MTD and concern exists regarding therapeutic activity of BGJ398 at this dose level, expansions with higher dose levels (1 to 3) may be considered at the MSKCC PI's discretion, with modification of the treatment schedule. In this setting BGJ398 will be administered daily for one week followed by 3 weeks off and imatinib will be taken daily throughout the 4 week cycle period (treatment schedule B). In the phase II portion of the study, patients will receive imatinib at 400 mg once daily (standard of care first line imatinib dose) and BGJ398 at the RP2D and treatment schedule identified in the phase Ib portion of the study. One cycle is 28 days.
Interventions
Eligibility Criteria
You may qualify if:
- Patients must have pathologically confirmed GIST.
- In the Phase Ib portion, must have locally advanced or metastatic GIST and have progressed on imatinib.
- In the Phase II portion, patients must be newly diagnosed or imatinib treatment naïve in the advanced/metastatic setting. Prior adjuvant imatinib therapy is allowed as long as disease recurrence was documented ≥90 days after last dose of imatinib and imatinib has not yet been restarted.
- Patients must be at least 18 years of age.
- Disease must be measurable by RECIST 1.1.
- ECOG Performance Status 0 or 1. Adequate renal, hepatic, and hematologic function as the following: Serum Creatinine ≤ 1.5 mg/dL, Total Serum Bilirubin ≤ 1.5 x upper limit of normal (ULN) unless due to Gilbert's Disease, Serum AST (SGOT) and/or ALT (SGPT) ≤ 2.5 x ULN (or ≤ 5.0 x ULN if considered due to tumor), ANC ≥ 1500/mm3, Platelets ≥ 100,000/mm3, and hemoglobin ≥ 10g/dL.
- Patients of childbearing potential must have a negative blood pregnancy test within 14 days of treatment. Patients must agree to use a reliable barrier method of birth control during and for 3 months following the last dose of study drug.
- Patient must have adequate cardiac function (left ventricular ejection fraction (LVEF) ≥50% as determined by a multigated acquisition (MUGA) scan or echocardiogram; and QTc interval ≤480 ms by Fridericia's formula (QTcF).
- Patient must be able to take oral medications.
- Patients must sign an informed consent document.
You may not qualify if:
- For phase I, prior intolerance to imatinib at a dose of 400 mg daily.
- For phase II, any receipt of cytotoxic, biologic, or immune therapy aimed to treat GIST except for adjuvant imatinib systemic therapy that concluded at least 90 days prior to registration. For Phase I, patients are eligible regardless of prior therapy.
- Chronic liver disease (e.g., cirrhosis)
- Known positive serology for HIV, active Hepatitis B, and/or active Hepatitis C infection.
- Patients have a history or current evidence of Central Serous Retinopathy (CSR) or retinal vein occlusion (RVO) or major predisposing factors to CSR or RVO (e.g. uncontrolled glaucoma or ocular hypertension) in the opinion of the study ophthalmologist.
- History of retinal degenerative disease
- Active corneal disorder or keratopathy (e.g. corneal abrasion, bullous keratopathy)
- Severe and/or uncontrolled medical disease, including:
- Uncontrolled diabetes mellitus (A1c \>8)
- Chronic Kidney Disease Stage III or higher (Creatinine Clearance \<60mL/min/m2 by Modified Diet in Renal Disease (MDRD) calculation)
- Active, uncontrolled infection Known active brain metastasis unless they have been treated and shown documented radiographic stability for 28 days.
- Known other active malignancy (other than malignancies which the investigator determines are unlikely to interfere with treatment and safety analysis).
- Patients have clinically significant cardiovascular disease, including any of the following
- Any history of acute coronary syndrome including myocardial infarction, stable or unstable angina, CABG, coronary angioplasty or stenting or known obstructive coronary artery disease.
- Symptomatic chronic heart failure (New York Heart Association Criteria, Class II-IV)
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Memorial Sloan Kettering Cancer Centerlead
- Dana-Farber Cancer Institutecollaborator
- M.D. Anderson Cancer Centercollaborator
- University of Pittsburghcollaborator
Study Sites (7)
Dana Farber Cancer Institute
Boston, Massachusetts, 02115, United States
Memoral Sloan Kettering Cancer Center
Basking Ridge, New Jersey, United States
Memorial Sloan Kettering Cancer Center @ Suffolk
Commack, New York, 11725, United States
Memorial Sloan Kettering Westchester
Harrison, New York, 10604, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Memorial Sloan Kettering at Mercy Medical Center
Rockville Centre, New York, United States
Md Anderson Cancer Center
Houston, Texas, 77030, United States
Related Publications (1)
Kelly CM, Shoushtari AN, Qin LX, D'Angelo SP, Dickson MA, Gounder MM, Keohan ML, Mcfadyen C, Sjoberg A, Singer S, DeMatteo RP, Hwang S, Heinemann MH, Francis JH, Antonescu CR, Chi P, Tap WD. A phase Ib study of BGJ398, a pan-FGFR kinase inhibitor in combination with imatinib in patients with advanced gastrointestinal stromal tumor. Invest New Drugs. 2019 Apr;37(2):282-290. doi: 10.1007/s10637-018-0648-z. Epub 2018 Aug 13.
PMID: 30101387DERIVED
Related Links
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. William Tap, MD
- Organization
- Memorial Sloan Kettering Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
William Tap, MD
Memorial Sloan Kettering Cancer Center
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 2, 2014
First Posted
October 6, 2014
Study Start
October 2, 2014
Primary Completion
March 25, 2019
Study Completion
March 25, 2019
Last Updated
March 30, 2020
Results First Posted
March 30, 2020
Record last verified: 2019-03