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Phase 1 Study of BLU-285 in Patients With Gastrointestinal Stromal Tumors (GIST) and Other Relapsed and Refractory Solid Tumors

This study is currently recruiting participants.
Verified October 2017 by Blueprint Medicines Corporation
Sponsor:
ClinicalTrials.gov Identifier:
NCT02508532
First Posted: July 27, 2015
Last Update Posted: October 17, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Blueprint Medicines Corporation
  Purpose
This is a Phase 1, open-label, first-in-human (FIH) study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antineoplastic activity of BLU-285, administered orally (PO), in adult patients with unresectable GIST or other relapsed or refractory solid tumors. The study consists of 2 parts, a dose-escalation part (Part 1) and an expansion part (Part 2).

Condition Intervention Phase
Gastrointestinal Stromal Tumors (GIST) Other Relapsed or Refractory Solid Tumors Drug: BLU-285 Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study of BLU-285 in Patients With Gastrointestinal Stromal Tumors (GIST) and Other Relapsed and Refractory Solid Tumors

Resource links provided by NLM:


Further study details as provided by Blueprint Medicines Corporation:

Primary Outcome Measures:
  • Part 1: Maximum tolerated dose (MTD) and Recommended Phase 2 dose (RP2D) of BLU-285 [ Time Frame: During cycle 1 (28 days) of treatment for MTD and at the end of every cycle (28 days) for RP2D for approximately 24 months or earlier if patient terminates from the study ]
  • Parts 1 and 2: Number of patients with adverse and serious adverse events and changes in physical findings, vital signs, clinical laboratory results and ECG findings [ Time Frame: Every cycle (28 days) for approximately 24 months or earlier if patient terminates from the study ]
  • Part 2: Overall response rate [ Time Frame: At Cycle 3 Day 1, then every 2 cycles through Cycle 13, then every 3 cycles thereafter. ]
    Either complete response (CR) or partial response (PR)


Secondary Outcome Measures:
  • Maximum plasma concentration of BLU-285 [ Time Frame: Every cycle (28 days) up to cycle 4 and at end of treatment (approximately 24 months or earlier if patient terminates from the study) ]
    Blood samples may be taken at pre-dose, and 0.5, 1, 2, 4, 6, 8 and 24 hrs post dose on Cycle 1 Day 1 and Cycle 1 Day 15, Pre-dose of Cycle 2 to 4, Day 1 and end of treatment (EOT)

  • Time to maximum plasma concentration of BLU-285 [ Time Frame: Every cycle (28 days) up to cycle 4 and at end of treatment (approximately 24 months or earlier if patient terminates from the study) ]
    Blood samples may be taken at pre-dose, and 0.5, 1, 2, 4, 6, 8 and 24 hrs post dose on Cycle 1 Day 1 and Cycle 1 Day 15, Pre-dose of Cycle 2 to 4, Day 1 and end of treatment (EOT)

  • Duration of response [ Time Frame: Overall median and at 3, 6, and 12 months ]
    CR, PR and stable disease (SD)

  • Progression-free survival [ Time Frame: Overall median and at 3, 6, and 12 months ]
  • Clinical benefit rate [ Time Frame: 16 weeks ]
    Rate of CR, PR, and SD

  • Response rate as defined by Choi Criteria [ Time Frame: At Cycle 3 Day 1, then every 2 cycles through Cycle 13, then every 3 cycles thereafter. ]
  • Median PFS on last prior anti-cancer therapy [ Time Frame: At Cycle 3 Day 1, then every 2 cycles through Cycle 13, then every 3 cycles thereafter. ]
  • KIT, PDGFRα, and other cancer-relevant mutations present in tumor tissue at baseline and EOT [ Time Frame: Screening period (Day -31 to Day 0 before first dose) and at the end of treatment ]
  • Change from baseline in levels of KIT and PDGFRα mutant allele fractions in peripheral blood [ Time Frame: Baseline, Cycle 1 day 15, Cycle 2 and 3 day 1 and at End of treatment (at approximately 24 months or earlier if patient terminates from the study) and at the EOT ]

Estimated Enrollment: 250
Study Start Date: August 2015
Estimated Study Completion Date: May 2019
Estimated Primary Completion Date: April 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BLU-285
BLU-285 capsules for oral administration. BLU-285 will be dosed daily for 28 day cycles.
Drug: BLU-285

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • For Part 1: Histologically- or cytologically-confirmed diagnosis of unresectable GIST or another advanced solid tumor. Patients with unresectable GIST must have disease that has progressed following imatinib and at least 1 of the following: sunitinib, regorafenib, sorafenib, dasatinib, pazopanib or an experimental kinase-inhibitor agent, or disease with a D842 mutation in the PDGFRα gene. Patients with an advanced solid tumor other than GIST must have relapsed or refractory disease without an available effective therapy.

OR For Part 2:

  • Group 1: Patients must have a confirmed diagnosis of unresectable GIST that has progressed following imatinib and at least 1 of the following: sunitinib, regorafenib, sorafenib, dasatinib, pazopanib, or an experimental kinase-inhibitor agent, and the patient does not have a D842V mutation in PDGFRα.
  • Group 2: Patients must have a confirmed diagnosis of unresectable GIST with a D842V mutation in the PDGFRα gene. The PDGFRα mutation will be identified by local or central assessment, either in an archival tissue sample or a new tumor biopsy obtained prior to treatment with BLU-285.
  • Group 3: Patients must have a confirmed diagnosis of unresectable GIST that has progressed and/or patients must have experienced intolerance to imatinib and not received additional kinase-inhibitor therapy. Patients must not have a known D842V mutation in PDGFRα.
  • Groups 1, 2 and 3: At least 1 measurable lesion defined by mRECIST 1.1 for patients with GIST.
  • Groups 1 and 2: A tumor sample (archival tissue or a new tumor biopsy) has been submitted for mutational testing.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

Exclusion Criteria:

  • QT interval corrected using Fridericia's formula (QTcF) >450 milliseconds
  • Platelet count <90,000/mL
  • Absolute neutrophil count <1000/mL
  • Hemoglobin <9 g/dL
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3 x the upper limit of normal (ULN) if no hepatic metastases are present; >5 × ULN if hepatic metastases are present
  • Total bilirubin >1.5 × ULN; >3 × ULN with direct bilirubin, >1.5 × ULN in the presence of Gilbert's Disease
  • Estimated (Cockroft-Gault formula) or measured creatinine clearance <40 mL/min Brain malignancy or metastases to the brain
  • History of a seizure disorder or requirement for anti-seizure medication
  • Group 3: Patients known to be KIT wild type.
  Contacts and Locations
Information from the National Library of Medicine

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): NCT02508532


Contacts
Contact: Blueprint Medicines 617-714-6707 studydirector@blueprintmedicines.com

Locations
United States, Florida
Sylvester Comprehensive Cancer Center Recruiting
Miami, Florida, United States, 33136
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
United States, Oregon
Oregon Health and Science University Recruiting
Portland, Oregon, United States, 97239
United States, Pennsylvania
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111
Belgium
Leuven Cancer Institute University Hospitals Leuven Recruiting
Leuven, Belgium, 3000
France
Centre Leon Berard Recruiting
Lyon, France, 69008
Institut Gustave Roussy Recruiting
Paris, France, 94805
Germany
University of Duisburg-Essen Recruiting
Essen, Germany, 45122
Netherlands
Erasmus MC Cancer Institute Recruiting
Rotterdam, Netherlands, 3015
United Kingdom
Royal Marsden Hospital Recruiting
London, United Kingdom, SW3 6JJ
Sponsors and Collaborators
Blueprint Medicines Corporation
  More Information

Responsible Party: Blueprint Medicines Corporation
ClinicalTrials.gov Identifier: NCT02508532     History of Changes
Other Study ID Numbers: BLU-285-1101
First Submitted: July 23, 2015
First Posted: July 27, 2015
Last Update Posted: October 17, 2017
Last Verified: October 2017

Additional relevant MeSH terms:
Neoplasms
Gastrointestinal Stromal Tumors
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases