BGJ398 in Combination With Imatinib Mesylate in Patients With Untreated Advanced Gastrointestinal Stromal Tumor (GIST)
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ClinicalTrials.gov Identifier: NCT02257541 |
Recruitment Status :
Completed
First Posted : October 6, 2014
Results First Posted : March 30, 2020
Last Update Posted : March 30, 2020
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Condition or disease | Intervention/treatment | Phase |
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Advanced Gastrointestinal Stromal Tumor (GIST) | Drug: BGJ398 Drug: Imatinib Mesylate | Phase 1 Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 16 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase Ib/II Study of BGJ398 in Combination With Imatinib Mesylate in Patients With Untreated Advanced Gastrointestinal Stromal Tumor (GIST) |
Actual Study Start Date : | October 2, 2014 |
Actual Primary Completion Date : | March 25, 2019 |
Actual Study Completion Date : | March 25, 2019 |

Arm | Intervention/treatment |
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Experimental: BGJ398 With Imatinib Mesylate
BGJ398 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.
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Drug: BGJ398 Drug: Imatinib Mesylate |
- Phase Ib Study: Number of Participants With Dose-Limiting Toxicities [ Time Frame: 1 year ]The phase Ib will be pursued in standard 3+3 format, based on toxicities encountered during the first cycle of therapy.
- Phase Ib Portion: Response Rate (RR) [ Time Frame: 32 weeks ]
(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
- Phase Ib Study: Response Rate (RR) [ Time Frame: 32 weeks ]
defined by RECIST 1.1 criteria and by CHOI criteria,and by EORTC 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

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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)
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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).
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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)
- Evidence of clinically significant cardiac arrhythmias and/or conduction abnormalities < 6 months prior to screening except atrial fibrillation (AF) and paroxysmal supraventricular tachycardia (PSVT)
- Any history of thrombotic cerebrovascular accident or other arterial thrombosis
- Uncontrolled arterial hypertension (systolic blood pressure >155 mmHg or diastolic >95 mmHg) despite appropriate medical therapy.
- History and/or current evidence of uncontrolled endocrine alterations of calcium/phosphate homeostasis, e.g., parathyroid disorders, history of parathyroidectomy, tumor lysis, tumoral calcinosis, etc.
- Impairment of gastrointestinal function or gastrointestinal disease (e.g., uncontrolled ulcerative disease; uncontrolled nausea, vomiting, diarrhea; chronic malabsorption syndrome).
- Patients with major surgery within 3 weeks prior to study entry or who have not recovered from side effects of such procedure.
- Women who are pregnant or lactating.
- Sexually active males, unless they use a condom during intercourse while taking the drug and for 15 days after stopping treatment. They should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid.
- Patients with any significant history of non-adherence to medical regimens or with inability to grant reliable informed consent.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02257541
United States, Massachusetts | |
Dana Farber Cancer Institute | |
Boston, Massachusetts, United States, 02115 | |
United States, New Jersey | |
Memoral Sloan Kettering Cancer Center | |
Basking Ridge, New Jersey, United States | |
United States, New York | |
Memorial Sloan Kettering Cancer Center @ Suffolk | |
Commack, New York, United States, 11725 | |
Memorial Sloan Kettering Westchester | |
Harrison, New York, United States, 10604 | |
Memorial Sloan Kettering Cancer Center | |
New York, New York, United States, 10065 | |
Memorial Sloan Kettering at Mercy Medical Center | |
Rockville Centre, New York, United States | |
United States, Texas | |
Md Anderson Cancer Center | |
Houston, Texas, United States, 77030 |
Principal Investigator: | William Tap, MD | Memorial Sloan Kettering Cancer Center |
Documents provided by Memorial Sloan Kettering Cancer Center:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | Memorial Sloan Kettering Cancer Center |
ClinicalTrials.gov Identifier: | NCT02257541 |
Other Study ID Numbers: |
14-140 |
First Posted: | October 6, 2014 Key Record Dates |
Results First Posted: | March 30, 2020 |
Last Update Posted: | March 30, 2020 |
Last Verified: | March 2019 |
BGJ398 Imatinib Mesylate 14-140 |
Gastrointestinal Stromal Tumors Neoplasms, Connective Tissue Neoplasms, Connective and Soft Tissue Neoplasms by Histologic Type Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Digestive System Diseases |
Gastrointestinal Diseases Imatinib Mesylate Infigratinib Antineoplastic Agents Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |