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

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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

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).

Condition or disease Intervention/treatment Phase
Gastrointestinal Stromal Tumors (GIST) Other Relapsed or Refractory Solid Tumors Drug: Avapritinib Phase 1

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 250 participants
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
Actual Study Start Date : August 2015
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : January 2021


Arm Intervention/treatment
Experimental: Avapritinib (formerly BLU-285)
Avapritinib tablets for oral administration. Avapritinib will be dosed daily for 28 day cycles.
Drug: Avapritinib



Primary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 :
  1. 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)

  2. 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)

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

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

  6. 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. ]
  7. 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. ]
  8. 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 ]
  9. 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 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
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 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.

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


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Sponsors and Collaborators
Blueprint Medicines Corporation

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Blueprint Medicines Corporation
ClinicalTrials.gov Identifier: NCT02508532     History of Changes
Other Study ID Numbers: BLU-285-1101
First Posted: July 27, 2015    Key Record Dates
Last Update Posted: May 14, 2019
Last Verified: May 2019

Keywords provided by Blueprint Medicines Corporation:
cancer gist
gastrointestinal stromal tumor
gist cancer
2L GIST
GIST second line
GIST gleevec
GIST imatinib
Second-line GIST clinical trial
BLU-285
BLU 285
BLUE-285
BLUE 285
Avapritinib
GIST imatinib relapse
GIST gleevec relapse
GIST KIT
GIST relapse
GIST refractory
GIST imatinib intolerance
GIST TKI treatment
GIST tyrosine kinase inhibitor treatment
GIST TKI
GIST tyrosine kinase inhibitor
Advanced GIST
GIST mutations
GIST treatments
Blueprint GIST
Relapsed GIST clinical trial
Refractory GIST clinical trial
KIT-mutant GIST

Additional relevant MeSH terms:
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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