Multicenter Phase 2 Trial of ARQ 197 for Subjects With Relapsed or Refractory Germ Cell Tumors
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 of equal to or less than
4. Documented progression during or following equal to or greater than 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
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
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 equal to or greater than 75 times 10^9/L;
- Hemoglobin equal to or greater than 9.0 g/dL;
- Absolute neutrophil count (ANC) equal to or greater than 1.5 times 10^9/L;
- Total bilirubin equal to or less than 2.5 mg/dL;
- Alanine aminotransaminase (ALT) and aspartate aminotransaminase (AST) equal to
or less than 2.5 times the upper limit of normal (ULN) (equal to or less than 5
times the ULN for subjects with liver metastases);
- Serum creatinine equal to or less than 1.5 times the 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
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 equal to or greater than 3 years prior to enrollment is
2. History of cardiac disease:
- Congestive heart failure defined as Class II to IV per New York Heart
- Active coronary artery disease.
- Previously diagnosed bradycardia or other cardiac arrhythmia defined as equal to
or greater than Grade 2 according to National Cancer Institute (NCI) Common
Terminology Criteria for Adverse Events (CTCAE), version 4.0, or uncontrolled
- Myocardial infarction that occurred within 6 months prior to study entry
(myocardial infarction that occurred greater than 6 months prior to study entry
3. Active clinically serious infection(s) defined as equal to or greater than Grade 2
according to NCI CTCAE, version 4.0.
4. Known metastatic brain or meningeal tumors, unless the subject is greater than 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 ARQ197.
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.