MULTICENTER PHASE 2 TRIAL OF ARQ 197 FOR SUBJECTS WITH RELAPSED OR REFRACTORY GERM CELL TUMORS

Phase 1

• Conditions: Germ cell tumors (GCT) including testicular and non-central nervous system (non-CNS) extragonadal types.; MedDRA version: 12.0Level: LLTClassification code 10061184Term: Germ cell cancer

• Registration Number: EUCTR2009-015400-26-FR
• Lead Sponsor: Daiichi Sankyo Pharma Development

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2009-12-04
• Study Completion: 2011-12-01
• Last Update Posted: 18 October 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Male
• Target Recruitment: 41

Inclusion Criteria

Subjects must satisfy all of the following criteria to be included in the clinical study.
1. Histologically-confirmed non-CNS GCT, both seminomas and nonseminomas are allowed.
2. Male subjects 16 years of age or older.
3. Eastern Cooperative Oncology Group (ECOG) performance status =1.
4. Documented progression during or following = 1 prior platinum-containing chemotherapy regimen(s) (no limit to number of lines of prior treatment), and considered platinum-resistant by the Investigator. Subjects who have progressed or whose tumors have recurred after stem cell transplantation are also allowed.
5. All subjects must have either declined or not be a candidate for curative therapy. In general, this means a subject would have to have progressive disease (PD) after receiving high-dose chemotherapy, have certain features making them ineligible for high-dose chemotherapy, or have refused high-dose chemotherapy despite being informed of its curative potential.
6. Subjects must have radiographically measurable disease as defined by RECIST 1.1 and meet one of the following criteria:
· Documented germ cell tumor progression based on radiographic measurements;
· Elevated serum tumor markers in case of radiographically measured stable disease.
7. Subjects should be able to provide written informed consent, comply with protocol visits and procedures, be able to take oral medication, and not have any active infection or chronic co-morbidity that would interfere with therapy.
8. Subjects must agree to use double-barrier contraceptive measures or avoidance of intercourse during the study and for 90 days after the last dose of study drug.
9. Adequate bone marrow, liver, and renal functions, defined as:
· Platelet count = 75 × 109/L
· Hemoglobin = 9.0 g/dL
· Absolute neutrophil count (ANC) = 1.5 × 109/L
· Total bilirubin = 2.5 mg/dL
· Alanine aminotransaminase (ALT) and aspartate aminotransaminase (AST) = 2.5 × upper limit of normal (ULN) (= 5 x ULN for subjects with liver metastases)
· Serum creatinine =1.5 × ULN
10.Subjects must be fully informed about their illness and the investigational nature of the study protocol (including foreseeable risks and possible side effects)
and must sign and date an Independent Ethics Committee- or Institutional Review Board-approved informed consent form (including Health Insurance
Portability and Accountability Act authorization, if applicable) before performance of any study-specific procedures or tests.

Are the trial subjects under 18? yes
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Potential subjects who meet ANY of the following exclusion criteria are not eligible for enrollment into this clinical study.
1. Previous or concurrent cancer that is distinct from GCT in primary site or histology, EXCEPT treated basal cell carcinoma, superficial bladder tumors (Ta, Tis & T1). Any cancer curatively treated = 3 years prior to enrollment is permitted.
2. History of cardiac disease:
· Congestive heart failure defined as Class II to IV per New York Heart Association classification;
· Active coronary artery disease;
· Previously diagnosed bradycardia or other cardiac arrhythmia defined as = Grade 2 according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, or uncontrolled hypertension;
· Myocardial infarction that occurred within 6 months prior to study entry (myocardial
infarction that occurred > 6 months prior to study entry is permitted).
3. Active clinically serious infection(s) defined as = Grade 2 according to NCI CTCAE, version 4.0.
4. Known metastatic brain or meningeal tumors, unless the subject is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of first dose of study drug and is clinically stable (no concomitant therapy, including supportive therapy with steroids or anticonvulsant medications) with respect to the tumor at the time of first dose of study drug.
5. Any primary CNS GCT.
6. Concurrent treatment with anticancer therapies including cytotoxic chemotherapy, immunotherapy, radiotherapy, vaccines or investigational therapy during the study or within 3 weeks of first dose of study drug.
7. Any major surgical procedure within 3 weeks prior to first dose of study drug.
8. Prior therapy with c-MET inhibitors, including ARQ 197.
9. Substance abuse or medical, psychological or social conditions that may, in the opinion of the Investigator, interfere with the subject’s participation in the clinical study or evaluation of the clinical study results.
10. Any condition that is unstable or that could jeopardize the safety of the subject and the subject’s protocol compliance, including known human immunodeficiency virus, hepatitis B virus or hepatitis C virus infection.
11.Inability to swallow oral medications.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective is to determine the objective response rate (ORR) after 4 cycles of therapy with ARQ 197 in subjects with GCT.;Secondary Objective: The secondary objectives are the following:<br>- To determine the progression free survival (PFS) rate at 12 weeks from enrollment.<br>- To determine the median overall survival among subjects treated with ARQ 197.<br>- To determine the safety and tolerability of ARQ 197 in this subject population.;Primary end point(s): The primary endpoint is the ORR of subjects treated with ARQ 197, after 4 cycles of therapy.