Study at several locations, randomized, double-blind with crenolanib in comparison with placebo in patients with advanced or metastatic gastrointestinal stromal tumors with a specific mutation (D842V) in the PDGFRA gene.
- Conditions
- Advanced or metastatic gastrointestinal stromal tumor (GIST)MedDRA version: 20.0 Level: LLT Classification code 10062427 Term: Gastrointestinal stromal tumor System Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-000287-34-DE
- Lead Sponsor
- Arog Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 120
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. Disease progression per modified RECIST 1.1 within 6 months of randomization
4. Subjects (male or female) = 18 years of age
5. Adequate bone marrow function, defined as:
- ANC of = 1000 /µL
- Platelet count of = 75 x 10^9/L
6. Adequate hepatic function, defined as:
- Serum total bilirubin within normal limits
- Serum aspartate aminotransferase (AST) = 2.0 x upper limit of normal (ULN)
- Serum alanine aminotransferase (ALT) = 2.0 x ULN
7. Adequate renal function, defined as:
- Serum creatinine = 1.5 x ULN or
- Creatinine clearance estimate of = 50 mL/min (as calculated according to Cokcroft-Gault formula or MDRD formula for subjects > 65 years).
8. Female subjects with reproductive potential must have negative serum or urine pregnancy test
Female subjects who meet at least one of the following criteria are defined as women of non-reproductive potential:
- =50 years old and naturally amenorrheic for = 1 year
- Permanent premature ovarian failure confirmed by a gynecologist
- Previous bilateral salpingo-oophorectomy
- XY genotype, Turner’s syndrome, or uterine agenesis
9. Prior treatment with imatinib, sunitinib, regorafenib, dasatinib and/or nilotinib is allowed. Recovered from prior treatment-related toxicity to Grade = 2 per CTCAE v4.03 or the subject's baseline preceding the prior treatment.
10. Eastern Cooperative Oncology Group (ECOG) performance status of = 2
11. Adequate contraception:
- Female subjects with reproductive potential in combination with their partner must use 2 forms of highly effective methods of contraception during study treatment and for at least 30 days after ending treatment
- Male subjects in combination with their partner must use 2 forms of highly effective methods of contraception during study treatment and for at least 90 days after ending treatment
12. Written informed consent before any study-specific procedure is performed
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 80
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40
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)
- Active infection with HBV is defined as:
o Acute hepatitis B (diagnosed < 6 months prior to randomization), or
o Serologic test positive for HBV surface antigen (HBsAg) positive, or
o Serologic test positive for immunoglobulin (IgM) to HBV core antigen (IgM anti-HBc)
- Active infection with HCV is defined as:
o Acute hepatitis C (diagnosed < 6 months prior to randomization), or
o Positive for HCV ribonucleic acid (RNA)
Subjects with history of positive anti-HCV screening test (e.g. enzyme immune-assay [EIA], chemiluminescence immunoassay [CIA], or recombinant immunoblot assay [RIA]) should be tested for HCV RNA
3. History of other malignancy within the past 3 years, except:
- Malignancy treated with curative intent and with no evidence of disease and considered to be at low risk of recurrence by the treating physician
- Adequately treated non-melanoma skin cancer or lentigo maligna with no evidence of disease
- Adequately treated cervical carcinoma in situ with no evidence of disease
- Adequately treated breast ductal carcinoma in situ with no evidence of disease
- Adequately treated prostatic intraepithelial neoplasia with no evidence of disease
- Adequately treated urothelial papillary non-invasive carcinoma or carcinoma in situ with no evidence of disease
4. Any disorder that compromises the subject’s ability to give written informed consent and/or to comply with study procedures
5. Any severe and/or uncontrolled medical or psychiatric conditions that in the opinion of the investigator, may prevent the subject from completing the study, interfere with the evaluation of safety and/or efficacy, or interfere with the interpretation of the study results
6. Female subject who is pregnant or breastfeeding, or planning to become pregnant within 30 days after ending treatment
7. 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 halflife in subject is known) prior to randomization, whichever is shorter
8. Prior administration of crenolanib
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To compare the treatment effect of crenolanib with that of placebo on prolonging progression-free survival (PFS) in subjects with advanced or metastatic GIST with a PDGFRA D842V mutation.;Secondary Objective: To compare the treatment effect of crenolanib with that of placebo on overall survival (OS) and objective response rate (ORR).;Primary end point(s): Progression-free survival (PFS);Timepoint(s) of evaluation of this end point: 35 months
- Secondary Outcome Measures
Name Time Method <br> Secondary end point(s): - Overall survival<br> - Objective response rate (based on modified RECIST 1.1)<br> ;Timepoint(s) of evaluation of this end point: 35 months