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

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02508532
Recruitment Status : Active, not recruiting
First Posted : July 27, 2015
Last Update Posted : May 14, 2019
Sponsor:
Information provided by (Responsible Party):
Blueprint Medicines Corporation

Tracking Information
First Submitted Date  ICMJE July 23, 2015
First Posted Date  ICMJE July 27, 2015
Last Update Posted Date May 14, 2019
Actual Study Start Date  ICMJE August 2015
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 22, 2017)
  • Part 1: Maximum tolerated dose (MTD) and Recommended Phase 2 dose (RP2D) of avapritinib [ 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)
Original Primary Outcome Measures  ICMJE
 (submitted: July 23, 2015)
  • 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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 22, 2017)
  • Maximum plasma concentration of avapritinib [ 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 avapritinib [ 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: July 23, 2015)
  • 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE (NAVIGATOR) Study of BLU-285 in Patients With Gastrointestinal Stromal Tumors (GIST) and Other Relapsed and Refractory Solid Tumors
Official Title  ICMJE A Phase 1 Study of BLU-285 in Patients With Gastrointestinal Stromal Tumors (GIST) and Other Relapsed and Refractory Solid Tumors
Brief Summary 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 avapritinib (formerly 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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Gastrointestinal Stromal Tumors (GIST)
  • Other Relapsed or Refractory Solid Tumors
Intervention  ICMJE Drug: Avapritinib
Study Arms  ICMJE Experimental: Avapritinib (formerly BLU-285)
Avapritinib tablets for oral administration. Avapritinib will be dosed daily for 28 day cycles.
Intervention: Drug: Avapritinib
Publications * Gebreyohannes YK, Wozniak A, Zhai ME, Wellens J, Cornillie J, Vanleeuw U, Evans E, Gardino AK, Lengauer C, Debiec-Rychter M, Sciot R, Schöffski P. Robust Activity of Avapritinib, Potent and Highly Selective Inhibitor of Mutated KIT, in Patient-derived Xenograft Models of Gastrointestinal Stromal Tumors. Clin Cancer Res. 2019 Jan 15;25(2):609-618. doi: 10.1158/1078-0432.CCR-18-1858. Epub 2018 Oct 1.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: October 13, 2017)
250
Original Estimated Enrollment  ICMJE
 (submitted: July 23, 2015)
60
Estimated Study Completion Date  ICMJE January 2021
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 avapritinib.
  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   France,   Germany,   Italy,   Korea, Republic of,   Netherlands,   Poland,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02508532
Other Study ID Numbers  ICMJE BLU-285-1101
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Blueprint Medicines Corporation
Study Sponsor  ICMJE Blueprint Medicines Corporation
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Blueprint Medicines Corporation
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP