Clinical Trials /

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

NCT02508532

Description:

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).

Related Conditions:
  • Gastrointestinal Stromal Tumor
  • Malignant Solid Tumor
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Phase 1 Study of BLU-285 in Patients With Gastrointestinal Stromal Tumors (<span class="go-doc-concept go-doc-disease">GIST</span>) and Other Relapsed and Refractory Solid Tumors

Title

  • Brief Title: Phase 1 Study of BLU-285 in Patients With Gastrointestinal Stromal Tumors (GIST) and Other Relapsed and Refractory Solid Tumors
  • Official Title: A Phase 1 Study of BLU-285 in Patients With Gastrointestinal Stromal Tumors (GIST) and Other Relapsed and Refractory Solid Tumors
  • Clinical Trial IDs

    NCT ID: NCT02508532

    ORG ID: BLU-285-1101

    Trial Conditions

    Gastrointestinal Stromal Tumors (GIST)

    Other Relapsed or Refractory Solid Tumors

    Trial Interventions

    Drug Synonyms Arms
    BLU-285 BLU-285

    Trial 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).

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    BLU-285 Experimental 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. BLU-285

    Eligibility 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 PDGFR 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 PDGFR.

    - Group 2: Patients must have a confirmed diagnosis of unresectable GIST with a D842
    mutation in the PDGFR gene. The PDGFR 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

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Maximum tolerated dose (MTD) and Recommended Phase 2 dose (RP2D) of BLU-285

    Number of patients with adverse and serious adverse events and changes in physical findings, vital signs, clinical laboratory results and ECG findings

    Secondary Outcome Measures

    Maximum plasma concentration of BLU-285

    Time to maximum plasma concentration of BLU-285

    Overall Response Rate

    Duration of Response

    KIT and PDGFR mutations present in tumor tissue at baseline and EOT

    Change from baseline in levels of KIT and PDGFR mutant allele fractions in peripheral blood

    Trial Keywords