Randomized Trial of Crenolanib in Subjects With D842V Mutated GIST

A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial of Crenolanib in Subjects With Advanced or Metastatic Gastrointestinal Stromal Tumors With a D842V Mutation in the PDGFRA Gene

This is a multicenter, randomized, double-blinded, placebo-controlled, trial of oral crenolanib versus oral placebo in combination with best supportive care in subjects with advanced or metastatic GIST with a D842V mutation in the PDGFRA gene. Approximately 120 subjects will be randomized in a 2:1 ratio to receive either crenolanib 100 mg or matching placebo orally (PO) 3 times daily (TID) in combination with best supportive care.

Study Overview

• Status: Unknown
• Conditions: GIST With D842V Mutated PDGFRA Gene
• Intervention / Treatment: Drug: Placebo; Drug: Crenolanib

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Bordeaux, France
    • Institut Bergonie
  • Lyon, France, 69008
    • Centre Leon Berard
  • Marseille, France
    • La Timone University hospital
  • Reims, France
    • Centre Hospitalier Universitaire (CHU) de Reims
• Germany
  • Berlin, Germany
    • HELIOS Klinikum Berlin-Buch
  • Mannheim, Germany, 68167
    • Mannheim University Medical Centre, University of Heidelberg
  • Munich, Germany
    • Universitätsklinikum München
• Italy
  • Bologna, Italy
    • Policlinico S. Orsola-Malpighi
  • Milan, Italy, 20133
    • Istituto Nazionale Tumori
  • Rome, Italy
    • Institut Regina Elena / IFO
  • Turin, Italy
    • Candiolo Cancer Institute - FPO, IRCCS
• Norway
  • Oslo, Norway
    • University Hospital The Norwegian Radium Hospital
• Poland
  • Warsaw, Poland
    • M Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology
• Spain
  • Barcelona, Spain
    • Vall d'Hebron University Hospital
  • Madrid, Spain
    • Hospital Universitario Puerta de Hierro
  • Sevilla, Spain
    • Hospital Virgen del Rocío
  • Valencia, Spain
    • Fundación Instituto Valenciano de Oncología
• United States
  • California
    • Santa Monica, California, United States, 90403
      • Sarcoma Oncology Center
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Cancer Institute
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Histologically or cytologically-confirmed advanced or metastatic GIST with a D842V mutation in the PDGFRA gene as determined by central laboratory testing

2. Measurable disease as per modified RECIST 1.1

   • A lesion in an area that was previously treated with local therapy (e.g. radiation, surgery, or cryotherapy) can be considered measurable disease as long as there is objective evidence of progression of the lesion prior to randomization

3. Subjects (male or female) ≥ 18 years of age
4. Female subjects with reproductive potential must have negative serum or urine pregnancy test
5. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2

Exclusion Criteria:

1. Severe liver disease (e.g. cirrhosis, non-alcoholic steatohepatitis, sclerosing cholangitis)
2. Known, active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV)
3. Female subject who is pregnant or breastfeeding, or planning to become pregnant within 30 days after ending treatment
4. Systemic anti-cancer treatment (e.g. chemotherapy, tyrosine kinase inhibitors, immunotherapy, or investigational agents) or investigational device within 3 weeks or 5 half-lives (if the drug's half-life in subject is known) prior to randomization, whichever is shorter

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Crenolanib Arm; Investigational product (crenolanib)	Drug: Crenolanib; Other Names: Crenolanib Besylate
Placebo Comparator: Placebo Arm; Matching placebo	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival (PFS) will be measured from the date of randomization to the date of the first objective radiological disease progression according to centralized committee assessment using modified RECIST version 1.1 or death.	3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival (OS) will be measured from the date of randomization to the date of death from any cause. OS will be estimated using the Kaplan-Meier method.	3 years

Collaborators and Investigators

• Sponsor: Arog Pharmaceuticals, Inc.
• Collaborators: Centre Leon Berard; Fox Chase Cancer Center

Study record dates

Study Major Dates

• Study Start: August 1, 2016
• Primary Completion (Anticipated): August 1, 2021
• Study Completion (Anticipated): August 1, 2021

Study Registration Dates

• First Submitted: July 21, 2016
• First Submitted That Met QC Criteria: July 25, 2016
• First Posted (Estimate): July 28, 2016

Study Record Updates

• Last Update Posted (Actual): January 22, 2021
• Last Update Submitted That Met QC Criteria: January 21, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Antineoplastic Agents; Crenolanib
• Other Study ID Numbers: ARO-012; 2015-000287-34 (EudraCT Number)