Randomized Trial of Crenolanib in Subjects With D842V Mutated GIST

NCT02847429 | Unknown Phase 3 DMC

• 2 other identifiers: ARO-0122015-000287-34
• Study Type: interventional
• Target: 120
• Locations: 7 countries
• Sites: 23

Brief Summary

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.

Conditions

GIST With D842V Mutated PDGFRA Gene

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• 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

Study Arms (2)

Crenolanib Arm

EXPERIMENTAL

Investigational product (crenolanib)

Drug: Crenolanib

Placebo Arm

PLACEBO COMPARATOR

Matching placebo

Drug: Placebo

Interventions

Crenolanib DRUG

Also known as: Crenolanib Besylate

Crenolanib Arm

Placebo DRUG

Placebo Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically-confirmed advanced or metastatic GIST with a D842V mutation in the PDGFRA gene as determined by central laboratory testing
• 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
• Subjects (male or female) ≥ 18 years of age
• Female subjects with reproductive potential must have negative serum or urine pregnancy test
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2

You may not qualify if:

• Severe liver disease (e.g. cirrhosis, non-alcoholic steatohepatitis, sclerosing cholangitis)
• Known, active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV)
• Female subject who is pregnant or breastfeeding, or planning to become pregnant within 30 days after ending treatment
• 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

Sponsors & Collaborators

• Arog Pharmaceuticals, Inc.: lead
• Centre Leon Berard: collaborator
• Fox Chase Cancer Center: collaborator

Study Sites (23)

Sarcoma Oncology Center

Santa Monica, California, 90403, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Duke Cancer Institute

Durham, North Carolina, 27710, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Institut Bergonie

Bordeaux, France

Location

Centre Leon Berard

Lyon, 69008, France

Location

La Timone University Hospital

Marseille, France

Location

Centre Hospitalier Universitaire (CHU) de Reims

Reims, France

Location

HELIOS Klinikum Berlin-Buch

Berlin, Germany

Location

Mannheim University Medical Centre, University of Heidelberg

Mannheim, 68167, Germany

Location

Universitätsklinikum München

Munich, Germany

Location

Policlinico S. Orsola-Malpighi

Bologna, Italy

Location

Istituto Nazionale Tumori

Milan, 20133, Italy

Location

Institut Regina Elena / IFO

Rome, Italy

Location

Candiolo Cancer Institute - FPO, IRCCS

Turin, Italy

Location

University Hospital The Norwegian Radium Hospital

Oslo, Norway

Location

M Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology

Warsaw, Poland

Location

Vall d'Hebron University Hospital

Barcelona, Spain

Location

Hospital Universitario Puerta de Hierro

Madrid, Spain

Location

Hospital Virgen del Rocio

Seville, Spain

Location

Fundación Instituto Valenciano de Oncología

Valencia, Spain

Location

MeSH Terms

Interventions

crenolanib

Study Officials

• Jean-Yves Blay, MD

  Centre Leon Berard

  PRINCIPAL INVESTIGATOR

• Margaret von Mehren, MD

  Fox Chase Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2016
• First Posted: July 28, 2016
• Study Start: August 1, 2016
• Primary Completion: August 1, 2021
• Study Completion: August 1, 2021
• Last Updated: January 22, 2021

Record last verified: 2021-01

Locations

IT (4); PL (1); ES (4); NO (1); US (6); FR (4); DE (3)