Try our beta test site

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. (see Contacts and Locations)
Verified January 2017 by Blueprint Medicines Corporation
Sponsor:
Information provided by (Responsible Party):
Blueprint Medicines Corporation
ClinicalTrials.gov Identifier:
NCT02508532
First received: July 23, 2015
Last updated: January 3, 2017
Last verified: January 2017
  Purpose
This is a Phase 1, open-label, first-in-human (FIH) dose-escalation study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary 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: 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:
  • 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 ]
  • 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 ]

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)

  • Overall Response Rate [ Time Frame: 16 Weeks ]
    Either complete response (CR) or partial response (PR)

  • Duration of Response [ Time Frame: 16 weeks ]
    CR, PR and stable disease (SD)

  • KIT and PDGFRα 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: 60
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. Each capsule contains 5, 10, 30 or 100 mg of active drug substance. BLU-285 will be dosed daily for 28 day cycles.
Drug: BLU-285

  Eligibility

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 agent that targets KIT, 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 agent that targets KIT, and the patient does not have a known D842 mutation in PDGFRα.
  • Group 2: Patients must have a confirmed diagnosis of unresectable GIST with a D842 mutation in the PDGFRα gene. The PDGFRα mutation should be identified by local assessment, either in an archival tissue sample or a new tumor biopsy.
  • 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
  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: NCT02508532

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

Locations
United States, Massachusetts
Recruiting
Boston, Massachusetts, United States
United States, Oregon
Recruiting
Portland, Oregon, United States
United States, Pennsylvania
Recruiting
Philadelphia, Pennsylvania, United States
Belgium
Recruiting
Leuven, Belgium
France
Recruiting
Lyon, France
Recruiting
Paris, France
Germany
Recruiting
Essen, Germany
Netherlands
Recruiting
Rotterdam, Netherlands
United Kingdom
Recruiting
London, United Kingdom
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 
Study First Received: July 23, 2015
Last Updated: January 3, 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

ClinicalTrials.gov processed this record on February 20, 2017