Clinical trial NCT02847429: Randomized Trial of Crenolanib in Subjects With D842V Mutated GIST
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: GIST With D842V Mutated PDGFRA Gene
Lead sponsor: Arog Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Centre Leon Berard
name: Fox Chase Cancer Center
First posted: 2016-07-28
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: 3 years
Secondary outcomes:
measure: 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.
timeFrame: 3 years
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: Sarcoma Oncology Center
state: California
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Durham
country: United States
facility: Duke Cancer Institute
state: North Carolina
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Bordeaux
country: France
facility: Institut Bergonie
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: La Timone University Hospital
city: Reims
country: France
facility: Centre Hospitalier Universitaire (CHU) de Reims
city: Berlin
country: Germany
facility: HELIOS Klinikum Berlin-Buch
city: Mannheim
country: Germany
facility: Mannheim University Medical Centre, University of Heidelberg
city: Munich
country: Germany
facility: Universitätsklinikum München
city: Bologna
country: Italy
facility: Policlinico S. Orsola-Malpighi
city: Milan
country: Italy
facility: Istituto Nazionale Tumori
city: Rome
country: Italy
facility: Institut Regina Elena / IFO
city: Turin
country: Italy
facility: Candiolo Cancer Institute - FPO, IRCCS
city: Oslo
country: Norway
facility: University Hospital The Norwegian Radium Hospital
city: Warsaw
country: Poland
facility: M Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology
city: Barcelona
country: Spain
facility: Vall d'Hebron University Hospital
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocio
city: Valencia
country: Spain
facility: Fundación Instituto Valenciano de Oncología
Study officials:
affiliation: Centre Leon Berard
name: Jean-Yves Blay, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fox Chase Cancer Center
name: Margaret von Mehren, MD
role: PRINCIPAL_INVESTIGATOR
References: