Trial record 5 of 1421 for:    gastrointestinal | Open Studies | Exclude Unknown | United States

BGJ398 in Combination With Imatinib Mesylate in Patients With Untreated Advanced Gastrointestinal Stromal Tumor (GIST)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Collaborators:
Dana-Farber Cancer Institute
M.D. Anderson Cancer Center
University of Pittsburgh
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT02257541
First received: October 2, 2014
Last updated: October 10, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention Phase
Advanced Gastrointestinal Stromal Tumor (GIST)
Drug: BGJ398
Drug: Imatinib Mesylate
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • Phase Ib study: Maximum tolerated dose [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    The phase Ib will be pursued in standard 3+3 format, based on toxicities encountered during the first cycle of therapy.

  • phase II portion: Response Rate (RR) [ Time Frame: 32 weeks ] [ Designated as safety issue: No ]
    (CR+PR, RECIST 1.1) and by CHOI criteria


Secondary Outcome Measures:
  • Phase Ib study: Response Rate (RR) [ Time Frame: 32 weeks ] [ Designated as safety issue: No ]
    defined by RECIST 1.1 criteria and by CHOI criteria,and by EORTC criteria


Estimated Enrollment: 62
Study Start Date: October 2014
Estimated Primary Completion Date: October 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BGJ398 With Imatinib Mesylate
Experimental: 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. 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 (once daily for 21 days on, 7 days off) at the recommended phase 2 dose established in the phase Ib portion of the study. One cycle is 28 days. For Phase II, study personnel will attempt to collect survival status for all patients after the end-of-study visit every 3 months via telephone, email, or other method for up to 3 years.
Drug: BGJ398 Drug: Imatinib Mesylate

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  • 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

    • History of acute coronary syndrome including myocardial infarction, unstable angina, CABG, coronary angioplasty or stenting < 6 months prior to screening
    • 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)
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02257541

Contacts
Contact: William Tap, MD 646-888-4163
Contact: Ping Chi, MD, PhD 646-888-4166

Locations
United States, Massachusetts
Dana Farber Cancer Institute Not yet recruiting
Boston, Massachusetts, United States, 02115
Contact: Andrew Wagner, MD         
Principal Investigator: Andrew Wagner, MD         
United States, New Jersey
Memoral Sloan Kettering Cancer Center Recruiting
Basking Ridge, New Jersey, United States
Contact: William Tap, MD    646-888-4163      
United States, New York
Memorial Sloan Kettering Cancer Center @ Suffolk Recruiting
Commack, New York, United States, 11725
Contact: William Tap, MD    646-888-4163      
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: William Tap, MD    646-888-4163      
Contact: Ping Chi, MD, PhD    646-888-4166      
Principal Investigator: William Tap, MD         
Memorial Sloan Kettering at Mercy Medical Center Recruiting
Rockville Centre, New York, United States
Contact: William Tap, MD    646-888-4163      
Memoral Sloan Kettering Cancer Center at Phelps Recruiting
Sleepy Hollow, New York, United States, 10591
Contact: William Tap, MD    646-888-4163      
United States, Texas
Md Anderson Cancer Center Not yet recruiting
Houston, Texas, United States, 77030
Contact: Neeta Somaiah, MD         
Principal Investigator: Neeta Somaiah, MD         
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Dana-Farber Cancer Institute
M.D. Anderson Cancer Center
University of Pittsburgh
Investigators
Principal Investigator: William Tap, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT02257541     History of Changes
Other Study ID Numbers: 14-140
Study First Received: October 2, 2014
Last Updated: October 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:
BGJ398
Imatinib Mesylate
14-140

Additional relevant MeSH terms:
Gastrointestinal Stromal Tumors
Gastrointestinal Neoplasms
Gastrointestinal Diseases
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Imatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 19, 2014