Non-CNS Germ Cell Tumors (Seminomas and Nonseminomas)Phase 2NCT01055067
ARQ 197 for Participants With Relapsed or Refractory Germ Cell Tumors
A Phase 2 study testing Tivantinib (ARQ 197) in people with Non-CNS Germ Cell Tumors (Seminomas and Nonseminomas), run by Daiichi Sankyo at 10 sites in 3 countries.
Trial summary
This is a multicenter, single-arm study for safety and efficacy. Read more about this study
- Who is it for?
- Ages 16 years and older, men only
- Conditions the study is for
- Non-CNS Germ Cell Tumors (Seminomas and Nonseminomas)
- What is being tested?
- Tivantinib (ARQ 197)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 10 sitesin 3 countries
- Study dates
- 2 Feb 2010to 30 Nov 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Histologically-confirmed non-central nervous system germ cell tumor (non-CNS GCT), both seminomas and nonseminomas are allowed.
- Male subjects 16 years of age or older.
- Eastern Cooperative Oncology Group (ECOG) performance status of equal to or less than 1.
- 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.
- 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.
- Subjects must have radiographically measurable disease as defined by RECIST 1.1 and meet one of the following criteria:
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- Documented germ cell tumor progression based on radiographic measurements;
- Elevated serum tumor markers in case of radiographically measured stable disease.
- 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.
- 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.
- 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.
- 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.
Who cannot join
- 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.
- 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).
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- Active clinically serious infection(s) defined as equal to or greater than Grade 2 according to NCI CTCAE, version 4.0.
- 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.
- Any primary CNS GCT.
- 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.
- Any major surgical procedure within 3 weeks prior to first dose of study drug.
- Prior therapy with c-MET inhibitors, including ARQ197.
- 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.
- 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.
- Inability to swallow oral medications.
Trial locations and contacts
10 sites in 3 countries.
10 sites in 3 countries
United States6 sites
Study site
Indianapolis, Indiana, 46202
Study site
Los Angeles, California, 90033
Study site
New York, New York, 10065
Study site
Orlando, Florida, 32806
Study site
Philadelphia, Pennsylvania, 19104
Study site
St Louis, Missouri, 63110
United Kingdom2 sites
Study site
Leeds, LS9 7TF
Study site
London, SM2 5PT
About this study
Official title: Multicenter Phase 2 Trial of ARQ 197 for Subjects With Relapsed or Refractory Germ Cell Tumors
This is a multicenter, single-arm study for safety and efficacy.
- Being tested
- Tivantinib (ARQ 197)
- Medical subject headings
- Seminoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tivantinib (ARQ 197)Drug
Also called Tivantinib
Capsule, 120 mg, BID (360 mg), approximately 112 days
| Study group | Role | What they receive |
|---|---|---|
| Tivantinib (ARQ 197) | Experimental | 3 capsules of 120 mg each, administered twice a day (once in the morning and once in the evening - total daily dose of 720 mg) in continuous 4-week cycles Receives: Drug: Tivantinib (ARQ 197) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Best Overall Response and Objective Response Rate Following Treatment With Tivantinib (ARQ 197) in Participants With Relapsed or Refractory Germ Cell Tumors
The best overall response was the best response (in the order of confirmed complete response [CR], confirmed partial response [PR], unconfirmed CR, unconfirmed PR, stable disease [SD], and progressive disease [PD]) among all overall responses recorded from the start of treatment until the participant withdrew from the study. Objective response was defined as the number of participants with confirmed CR and confirmed PR after 4 cycles of therapy with ARQ 197. According to Response Evaluation Criteria in Solid Tumors v 1.1, CR was defined as a disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, defined as at least a 20% increase in the sum of diameters of target lesions.
Measured: Baseline up to first objective response, up to 1 year 9 months postdose
Secondary outcomes (3)
Progression-Free Survival Following Treatment With Tivantinib (ARQ 197) in Participants With Relapsed or Refractory Germ Cell Tumors
Progression-free survival (PFS) is defined as the time from the date of the start of study treatment to the earlier of the dates of the first documentation of progressive disease (PD) or death due to any cause. According to Response Evaluation Criteria in Solid Tumors v 1.1, progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions.
Measured: Baseline up to progressive disease or death (whichever occurs first), up to 1 year 9 months postdose
Overall Survival Following Treatment With Tivantinib (ARQ 197) in Participants With Relapsed or Refractory Germ Cell Tumors
Overall survival (OS) was defined as the time from the date of the start of study treatment to the date of death due to any cause.
Measured: Baseline up to death (any cause), up to 1 year 9 months postdose
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Participants With Relapsed or Refractory Germ Cell Tumors
Treatment-emergent adverse events (TEAEs) were defined as an adverse event (AE) that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the first dose until 30 days after the last dose.
Measured: Baseline up to 30 days after last dose, up to 1 year 9 months postdose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2010 (estimated)
- Study start2 Feb 2010
- Primary completion30 Nov 2011
- Study completion30 Nov 2011
Why it stopped: The study was terminated early for futility according to the stopping rule of the Simon 2-stage design.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Non-CNS Germ Cell Tumors (Seminomas and Nonseminomas)Studies of the same condition, open and under way.
- More trials run by Daiichi SankyoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Daiichi Sankyo
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Study Leader, Study director, Daiichi Sankyo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01055067
- Sponsor's protocol ID
- ARQ197-A-U251
- Status last verified
- Mar 2021
- First submitted
- 21 Jan 2010
- Last updated
- 6 Apr 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter Phase 2 Trial of ARQ 197 for Subjects With Relapsed or Refractory Germ Cell Tumors
- ClinicalTrials.gov ID
- NCT01055067
- Acronym / sponsor ID
- ARQ197-A-U251
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated early for futility according to the stopping rule of the Simon 2-stage design.
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Daiichi SankyoIndustry (pharma, biotech, devices)
- Study start
- 2 Feb 2010 (actual)
- Primary completion
- 30 Nov 2011 (actual)
- Study completion
- 30 Nov 2011 (actual)
- First posted
- 25 Jan 2010 (estimated)
- Results
- Posted 9 Sep 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multicenter, single-arm study for safety and efficacy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tivantinib (ARQ 197) | Experimental | Drug: Tivantinib (ARQ 197)3 capsules of 120 mg each, administered twice a day (once in the morning and once in the evening - total daily dose of 720 mg) in continuous 4-week cycles |
Who may qualify
- Ages
- 16 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (18 listed)
- Histologically-confirmed non-central nervous system germ cell tumor (non-CNS GCT), both seminomas and nonseminomas are allowed.
- Male subjects 16 years of age or older.
- Eastern Cooperative Oncology Group (ECOG) performance status of equal to or less than 1.
- 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.
- 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.
Key exclusion criteria (15 listed)
- 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.
- History of cardiac disease:
- Active clinically serious infection(s) defined as equal to or greater than Grade 2 according to NCI CTCAE, version 4.0.
- 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.
- Any primary CNS GCT.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tivantinib (ARQ 197)Also: TivantinibCapsule, 120 mg, BID (360 mg), approximately 112 days | Drug | Tivantinib (ARQ 197) |
Primary outcome
Best Overall Response and Objective Response Rate Following Treatment With Tivantinib (ARQ 197) in Participants With Relapsed or Refractory Germ Cell Tumors
Time frame: Baseline up to first objective response, up to 1 year 9 months postdose
The best overall response was the best response (in the order of confirmed complete response [CR], confirmed partial response [PR], unconfirmed CR, unconfirmed PR, stable disease [SD], and progressive disease [PD]) among all overall responses recorded from the start of treatment until the participant withdrew from the study. Objective response was defined as the number of participants with confirmed CR and confirmed PR after 4 cycles of therapy with ARQ 197. According to Response Evaluation Criteria in Solid Tumors v 1.1, CR was defined as a disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, defined as at least a 20% increase in the sum of diameters of target lesions.
3 secondary outcomes
Progression-Free Survival Following Treatment With Tivantinib (ARQ 197) in Participants With Relapsed or Refractory Germ Cell Tumors
Time frame: Baseline up to progressive disease or death (whichever occurs first), up to 1 year 9 months postdose
Overall Survival Following Treatment With Tivantinib (ARQ 197) in Participants With Relapsed or Refractory Germ Cell Tumors
Time frame: Baseline up to death (any cause), up to 1 year 9 months postdose
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Participants With Relapsed or Refractory Germ Cell Tumors
Time frame: Baseline up to 30 days after last dose, up to 1 year 9 months postdose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Study Leader study director
Daiichi Sankyo
10 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tivantinib (ARQ 197) in people with Non-CNS Germ Cell Tumors (Seminomas and Nonseminomas), run by Daiichi Sankyo at 10 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 6 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, France, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Sep 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Best Overall Response and Objective Response Rate Following Treatment With Tivantinib (ARQ 197) in Participants With Relapsed or Refractory Germ Cell Tumors (time frame: Baseline up to first objective response, up to 1 year 9 months postdose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2021.