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Hormone-Resistant Prostate CancerPhase 2NCT01519414

Tivantinib in Treating Patients With Metastatic Prostate Cancer

A Phase 2 study testing Laboratory Biomarker Analysis and Tivantinib in people with Hormone-Resistant Prostate Cancer and Prostate Adenocarcinoma, run by National Cancer Institute (NCI) at 20 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This randomized phase II trial studies how well tivantinib works compared to placebo in treating patients with metastatic prostate cancer. Tivantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Laboratory Biomarker Analysis and Tivantinib
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
78 participants
Where
20 sitesUnited States
Study dates
11 Jan 2012to 18 Aug 2015
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 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must have histologically documented adenocarcinoma of the prostate with progressive systemic disease (either rising PSA or progression of disease on CT scan or magnetic resonance imaging [MRI] or bone scan) despite castrate levels of testosterone due to orchiectomy or luteinizing hormone-releasing hormone (LHRH) agonist or antagonist; castrate levels of testosterone must be maintained throughout the study
  • Evidence of metastatic disease on CT or bone imaging
  • Patients must have demonstrated evidence of progressive disease since the most recent change in therapy; progressive disease is defined as any one of the following (measurable disease, bone scan, or PSA progression):
  • Measurable disease progression: objective evidence of increase > 20% in the sum of the longest diameters (LD) of target lesions from the time of maximal regression or the appearance of one or more new lesions
  • Bone scan progression: appearance of two or more new lesions on bone scan attributable to prostate cancer will constitute progression
  • PSA progression: two successive rises from baseline PSA separated at least by one week with the last value >= 2 ng/mL
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  • Asymptomatic or minimally symptomatic from prostate cancer - no symptoms attributed to prostate cancer greater than grade I using NCI CTCAE version 4.0 grading of toxicities
  • Secondary hormonal therapies (e.g., abiraterone acetate, flutamide, estrogen) must be discontinued for at least 4 weeks prior to study enrollment unless the duration of the therapy was less than 8 weeks and there was no demonstrated decrease in PSA
  • Secondary hormonal therapies with bicalutamide or nilutamide must be discontinued for 6 weeks unless duration of therapy was less than 8 weeks and there was no demonstrated PSA decrease
  • Prior abiraterone (or investigational anti-androgen) use is allowed; these too will need to be discontinued at least 4 weeks prior to study enrollment
  • PSA prior to treatment must be >= 2 ng/ml
  • Castrate testosterone level (< 50 ng/dL)
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • No prior chemotherapy unless utilized in neoadjuvant/adjuvant setting and must have completed > 6 months prior to enrollment
  • Four weeks since major surgery or radiation therapy
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin within normal institutional limits
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.0 X institutional upper limit of normal
  • Creatinine within normal institutional limits OR creatinine clearance >= 40 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Patients must have signed an informed consent document stating that they understand the investigational nature of the proposed treatment
  • Men and any female partners of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation and for additional 2 months after finishing therapy; should a patient's sexual partner become pregnant or suspect she is pregnant while patient is participating in this study, he should inform the treating physician immediately
  • Bisphosphonate or denosumab therapy is permitted provided patients began therapy prior to registration and that they continue them as per the manufacturer's guidelines and/or per institutional practice; patients not taking ongoing bisphosphonate or denosumab therapy will not be permitted to start such therapy until they have completed 12 weeks of study treatment
  • Patients must be able to swallow pills to participate in the study

Who cannot join

  • Patients who have radiotherapy within 4 weeks or chemotherapy prior to entering the study or those who have not recovered (resolution to grade 1) from adverse events due to agents administered more than 4 weeks earlier; neoadjuvant/adjuvant chemotherapy for local disease is allowed if greater than 6 months have elapsed
  • Previous hepatocyte growth factor receptor (C-MET) inhibitor treatment (either monoclonal antibody to C-MET or human growth factor [HGF] or small molecule inhibitory to C-MET)
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition ARQ 197
  • Caution should be used with patients receiving inhibitors of cytochrome P450 family 2, subfamily C, polypeptide 19 (CYP2C19) and strong inhibitors of cytochrome P450 family 3, subfamily A, polypeptide4 (CYP3A4); additional hematologic testing will be advised if the medication cannot be substituted
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or known psychiatric illness/social situations that would limit compliance with study requirements
  • Known brain metastasis
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  • Current, recent (within 4 weeks of the first study drug administration), or concurrent planned participation in another investigational therapeutic study
  • Patients with a "currently active" second malignancy other than non-melanoma skin cancers are not to be registered; patients are not considered to have a "currently active" malignancy if they have completed therapy and are now considered to be at less than 30% risk for relapse (by their physician)
  • Patients may continue on a daily multi-vitamin and calcium/vitamin D supplements; all other herbal, alternative, and food supplements (i.e., PC-SPES, Saw Palmetto, St. John wort, etc.) must be discontinued before registration
  • New York Heart Association (NYHA) class III or greater congestive heart failure
  • History of myocardial infarction or unstable angina within 6 months prior to initial treatment
  • History of severely impaired lung function
  • Baseline electrocardiogram (ECG) abnormalities including first degree (PR interval > 210 ms), second degree, or third degree heart block (exception: patients with pacemakers may be enrolled); QRS prolongation or bundle branch block (QRS >= 120 ms), or QT prolongation (per institutional standard of care: Fridericia corrected QT interval [QTcF] or Bazett corrected QT interval [QTcB] >= 470 ms); other ECG abnormalities will need consideration by the treating investigator and enrollment is up to his/her discretion
  • Presence of non-healing wound, active ulcer, or untreated bone fracture
  • Known diabetics that have poorly controlled diabetes mellitus (glycated hemoglobin [HbA1c] >= 8.0%) or fasting glucose level >= 189 mg/dL (diabetic patient); patients may be potentially eligible once anti-diabetic agent(s) are either added or titrated to control their diabetes mellitus
  • Active liver disease (AST or ALT >= 2.0 times the upper limit of normal [ULN] or total bilirubin >= institutional ULN) or gallbladder disease; patients with known liver cirrhosis or severe hepatic impairment (Child-Pugh Class C) will also be excluded
  • A known history of human immunodeficiency virus (HIV) seropositivity
  • Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of ARQ 197 (e.g., uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or significant small bowel resection)
  • Patients with an active bleeding diathesis

Trial locations and contacts

20 sites in 1 country.

20 sites in 1 country

United States20 sites

  • University of Maryland/Greenebaum Cancer Center

    Baltimore, Maryland, 21201

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • Northwestern University

    Chicago, Illinois, 60611

  • Michael Reese Hospital

    Chicago, Illinois, 60616

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Case Western Reserve University

    Cleveland, Ohio, 44106

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Decatur Memorial Hospital

    Decatur, Illinois, 62526

  • NorthShore University HealthSystem-Evanston Hospital

    Evanston, Illinois, 60201

  • Fort Wayne Medical Oncology and Hematology Inc - Jefferson Boulevard

    Fort Wayne, Indiana, 46804

  • Ingalls Memorial Hospital

    Harvey, Illinois, 60426

  • Indiana University/Melvin and Bren Simon Cancer Center

    Indianapolis, Indiana, 46202

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

  • Illinois CancerCare-Peoria

    Peoria, Illinois, 61615

  • Southern Illinois University School of Medicine

    Springfield, Illinois, 62702

  • Mercy Hospital Saint Louis

    St Louis, Missouri, 63141

  • Moffitt Cancer Center

    Tampa, Florida, 33612

  • University of Maryland Saint Joseph Medical Center

    Towson, Maryland, 21204

  • MedStar Georgetown University Hospital

    Washington D.C., District of Columbia, 20007

Other trials in United States

About this study

Official title: A Randomized, Double-Blind, Placebo-Controlled Phase II Study of ARQ 197 (Tivantinib) in Men With Asymptomatic or Minimally Symptomatic Metastatic Castrate Resistant Prostate Cancer

This randomized phase II trial studies how well tivantinib works compared to placebo in treating patients with metastatic prostate cancer. Tivantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine progression-free survival (PFS) in men with minimally symptomatic or asymptomatic metastatic, castrate-resistant, chemotherapy-naïve prostate cancer treated with ARQ 197 (tivantinib).

SECONDARY OBJECTIVES:

  1. To determine the prostate-specific antigen (PSA) response rate at 12 weeks in men with metastatic, castrate-resistant, chemotherapy-naïve prostate cancer treated with ARQ 197.

II. To determine the radiographic response rate at 12 weeks based on Response Evaluation Criteria in Solid Tumors (RECIST) criteria on computed tomography (CT) scans and stability of bone lesions on bone scan in castrate-resistant, chemotherapy-naïve prostate cancer treated with ARQ 197.

III. To determine the proportion of patients who are progression-free at 12 weeks.

IV. To assess safety and tolerability in patients treated with ARQ 197 using the National Institute of Cancer (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 grading of toxicities.

TERTIARY OBJECTIVES:

  1. Evaluate markers of bone turnover. (Exploratory)

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive tivantinib orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Arm II: Patients receive placebo PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may crossover to Arm I.

After completion of study treatment, patients are followed up every 3 months for 6 months.

Being tested
Laboratory Biomarker Analysis, Placebo, Tivantinib
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Laboratory Biomarker AnalysisOther

    Optional correlative studies

  • PlaceboOther

    Also called placebo therapy, PLCB, sham therapy

    Given PO

  • TivantinibDrug

    Also called ARQ 197, ARQ-197, c-Met Inhibitor ARQ 197

    Given PO

Study groups in NCT01519414
Study groupRoleWhat they receive
Arm I (tivantinib)ExperimentalPatients receive tivantinib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Other: Laboratory Biomarker Analysis; Drug: Tivantinib
Arm II (placebo)Placebo comparatorPatients receive placebo PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may crossover to Arm I.
Receives: Other: Laboratory Biomarker Analysis; Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free Survival (PFS) Based on the RECIST Criteria

    The progression-free survival distributions between the two arms will be compared using log-rank tests. Progression-free survival curves will be constructed using the Kaplan-Meier product limit method, and additional analyses will be done using the Cox proportional hazards model.

    Measured: Time from study entry to the date of documented progression and/or death, assessed up to 6 months

Secondary outcomes (4)

  1. Changes in PSA Levels

    Evaluated and patterns graphically explored through waterfall plots.

    Measured: Baseline to 12 weeks

  2. Proportion of Patients Who Respond

    An assumed binomial distribution used. Summarized with their corresponding 95% binomial confidence intervals and compared in an exploratory manner between the two treatment arms. Dichotomized outcomes of response will be descriptively summarized and graphically evaluated using bar graphs.

    Measured: At 12 weeks

  3. PSA Response Rate

    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

    Measured: up to 12 weeks

  4. Incidence of Adverse Events Graded as 3, 4, or 5 Per NCI CTCAE Version 4.0

    Fisher's exact tests will be used to quantitatively compare the incidence of severe as well as specific toxicities of interest between the treatment arms and graphically assessed differences in maximum grades observed for toxicities between the arms.

    Measured: Up to 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2012 (estimated)
  2. Study start11 Jan 2012
  3. Primary completion18 Aug 2015
  4. Study completion18 Aug 2015

Resources

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
Randomised
Intervention model
Crossover
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
78 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01519414
Sponsor's protocol ID
NCI-2012-00237
Other IDs
NCI-2012-00237, CDR0000721410, OSU11132, OSU-11132, OSU 11132, 8986, N01CM00070, N01CM00071
Status last verified
Aug 2018
First submitted
25 Jan 2012
Last updated
12 Sep 2018

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Laboratory Biomarker Analysis and Tivantinib in people with Hormone-Resistant Prostate Cancer and Prostate Adenocarcinoma, run by National Cancer Institute (NCI) at 20 sites in United States.

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 24 inclusion and 19 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: finished, as of the sponsor's last update on 12 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in United States. 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. Some participants in this study may receive a placebo. 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 12 Sep 2018). 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?

Progression-free Survival (PFS) Based on the RECIST Criteria (time frame: Time from study entry to the date of documented progression and/or death, assessed up to 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01519414.

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 12 Sep 2018; AzTrials last refreshed its copy on 8 Nov 2026.

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