Advanced Gastrointestinal Stromal Tumor (GIST)Phase 1/2NCT02257541

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

A Phase 1/2 study testing BGJ398 and Imatinib Mesylate in people with Advanced Gastrointestinal Stromal Tumor (GIST), run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Advanced Gastrointestinal Stromal Tumor (GIST)
What is being tested?: BGJ398 and Imatinib Mesylate
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 16 participants
Where: 7 sitesUnited States
Study dates: 2 Oct 2014to 25 Mar 2019
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

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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.

Who cannot join

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

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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)
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.

Trial locations and contacts

7 sites in 1 country.

City, postcode or hospital

7 sites in 1 country

United States7 sites

Memoral Sloan Kettering Cancer Center
Basking Ridge, New Jersey
Dana Farber Cancer Institute
Boston, Massachusetts, 02115
Memorial Sloan Kettering Cancer Center @ Suffolk
Commack, New York, 11725
Memorial Sloan Kettering Westchester
Harrison, New York, 10604
Md Anderson Cancer Center
Houston, Texas, 77030
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Memorial Sloan Kettering at Mercy Medical Center
Rockville Centre, New York

Other trials in United States

About this study

Official title: A Phase Ib/II Study of BGJ398 in Combination With Imatinib Mesylate in Patients With Untreated Advanced Gastrointestinal Stromal Tumor (GIST)

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.

Conditions: Advanced Gastrointestinal Stromal Tumor (GIST)
Being tested: BGJ398, Imatinib Mesylate
Keywords: BGJ398, Imatinib Mesylate, 14-140

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BGJ398Drug
Imatinib MesylateDrug

Study groups in NCT02257541
Study group	Role	What they receive
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 (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. Receives: Drug: BGJ398; Drug: Imatinib Mesylate

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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
Measured: 32 weeks

Secondary outcomes (1)

Phase Ib Study: Response Rate (RR)
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
Measured: 32 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

2 Oct 201425 Mar 2019

First posted6 Oct 2014 (estimated)
Study start2 Oct 2014
Primary completion25 Mar 2019
Study completion25 Mar 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Advanced Gastrointestinal Stromal Tumor (GIST)Studies of the same condition, open and under way.
More trials run by Memorial Sloan Kettering Cancer CenterThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 16 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02257541
Sponsor's protocol ID: 14-140
Status last verified: Mar 2019
First submitted: 2 Oct 2014
Last updated: 30 Mar 2020
Results posted: Yes, on ClinicalTrials.gov

Publications

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.
PubMed 30101387

Study at a glance

From the registry record, last updated by the sponsor on 30 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase Ib/II Study of BGJ398 in Combination With Imatinib Mesylate in Patients With Untreated Advanced Gastrointestinal Stromal Tumor (GIST)
ClinicalTrials.gov ID: NCT02257541
Acronym / sponsor ID: 14-140
Conditions: Advanced Gastrointestinal Stromal Tumor (GIST)
Keywords: BGJ398, Imatinib Mesylate, 14-140
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 16 participants (actual)
Lead sponsor: Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
Collaborators: Dana-Farber Cancer Institute, M.D. Anderson Cancer Center, University of Pittsburgh
Study start: 2 Oct 2014 (actual)
Primary completion: 25 Mar 2019 (actual)
Study completion: 25 Mar 2019 (actual)
First posted: 6 Oct 2014 (estimated)
Results: Posted 30 Mar 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
BGJ398 With Imatinib Mesylate	Experimental	Drug: BGJ398, Drug: Imatinib MesylateBGJ398 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (10 listed)

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.

Key exclusion criteria (24 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
BGJ398	Drug	BGJ398 With Imatinib Mesylate
Imatinib Mesylate	Drug	BGJ398 With Imatinib Mesylate

Primary outcome

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

1 secondary outcome

Phase Ib Study: Response Rate (RR)
Time frame: 32 weeks

Results and safety

Results posted to the registry on 30 Mar 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Phase 1b, Dose Level -1	3	3
Phase 1b, Dose Level 1	8	8
Phase 1b, Dose Level 2	1	1
Phase 1b, Dose Level -2	3	3
Phase II	1	1

Primary outcome: Phase Ib Study: Number of Participants With Dose-Limiting Toxicities

Time frame: 1 year. Count of participants. Unit: Participants

Measure	Phase 1b, Dose Level -1 n = 3	Phase 1b, Dose Level 1 n = 8	Phase 1b, Dose Level 2 n = 1	Phase 1b, Dose Level -2 n = 3
Value	3	8	1	3

Primary outcome: Phase Ib Portion: Response Rate (RR)

Time frame: 32 weeks. Count of participants. Unit: Participants

Measure	Phase 1b, Dose Level -1 n = 3	Phase 1b, Dose Level 1 n = 8	Phase 1b, Dose Level 2 n = 1	Phase 1b, Dose Level -2 n = 3
Partial Response/PR	1	0	0	0
Stable Disease/SD	2	3	0	0
Progressive Disease/PD	0	3	1	3
Not reported due to withdrawn from study	0	2	0	0

1 secondary outcome is reported in the full results.

Adverse events

Time frame: 1 year. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Phase 1b, Dose Level -1	2 of 3 (66.7%)	3 of 3 (100%)	2 of 3
Phase 1b, Dose Level 1	7 of 8 (87.5%)	8 of 8 (100%)	3 of 8
Phase 1b, Dose Level 2:	1 of 1 (100%)	1 of 1 (100%)	0 of 1
Phase 1b, Dose Level -2	3 of 3 (100%)	3 of 3 (100%)	0 of 3
Phase II	0 of 1 (0%)	1 of 1 (100%)	0 of 1

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 30101387Kelly 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.
Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

William Tap, MD principal investigator

Memorial Sloan Kettering Cancer Center

7 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing BGJ398 and Imatinib Mesylate in people with Advanced Gastrointestinal Stromal Tumor (GIST), run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase Ib Study: Number of Participants With Dose-Limiting Toxicities (time frame: 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02257541, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2020.