Clinical trial NCT01055067: ARQ 197 for Participants With Relapsed or Refractory Germ Cell Tumors
Official title: Multicenter Phase 2 Trial of ARQ 197 for Subjects With Relapsed or Refractory Germ Cell Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Non-CNS Germ Cell Tumors (Seminomas and Nonseminomas)
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2010-01-25
Enrollment: 27
Sex: MALE
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a multicenter, single-arm study for safety and efficacy.


Eligibility criteria: Inclusion Criteria:

1. Histologically-confirmed non-central nervous system germ cell tumor (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 1.
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 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 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 tests.

Exclusion Criteria:

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 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 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 hypertension.
   * Myocardial infarction that occurred within 6 months prior to study entry (myocardial infarction that occurred greater than 6 months prior to study entry is permitted).
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.

Primary outcomes:
measure: Best Overall Response and Objective Response Rate Following Treatment With Tivantinib (ARQ 197) in Participants With Relapsed or Refractory Germ Cell Tumors
timeFrame: Baseline up to first objective response, up to 1 year 9 months postdose
Secondary outcomes:
measure: Progression-Free Survival Following Treatment With Tivantinib (ARQ 197) in Participants With Relapsed or Refractory Germ Cell Tumors
timeFrame: Baseline up to progressive disease or death (whichever occurs first), up to 1 year 9 months postdose
measure: Overall Survival Following Treatment With Tivantinib (ARQ 197) in Participants With Relapsed or Refractory Germ Cell Tumors
timeFrame: Baseline up to death (any cause), up to 1 year 9 months postdose
measure: Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Participants With Relapsed or Refractory Germ Cell Tumors
timeFrame: Baseline up to 30 days after last dose, up to 1 year 9 months postdose
Other outcomes:
Locations:
city: Los Angeles
country: United States
state: California
city: Orlando
country: United States
state: Florida
city: Indianapolis
country: United States
state: Indiana
city: Saint Louis
country: United States
state: Missouri
city: New York
country: United States
state: New York
city: Philadelphia
country: United States
state: Pennsylvania
city: Lyon cedex
country: France
city: Villejuif
country: France
city: Leeds
country: United Kingdom
city: London
country: United Kingdom
Study officials:
affiliation: Daiichi Sankyo
name: Clinical Study Leader
role: STUDY_DIRECTOR
References: