Trial record 1 of 1 for:    NCT01519414
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Tivantinib in Treating Patients With Metastatic Prostate Cancer

This study is currently recruiting participants.
Verified October 2013 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01519414
First received: January 25, 2012
Last updated: October 7, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Adenocarcinoma of the Prostate
Hormone-resistant Prostate Cancer
Recurrent Prostate Cancer
Stage IV Prostate Cancer
Drug: tivantinib
Other: placebo
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • PSA response rate [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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.

  • Changes in PSA levels [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Evaluated and patterns graphically explored through waterfall plots.

  • Radiographic response rate based on RECIST criteria [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
    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.

  • Proportion of patients who respond [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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.

  • Incidence of toxicities graded as 3, 4, or 5 per NCI CTCAE v 4.0 [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 78
Study Start Date: January 2012
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (tivantinib)
Patients receive tivantinib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: tivantinib
Given PO
Other: laboratory biomarker analysis
Optional correlative studies
Placebo Comparator: Arm II (placebo)
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.
Other: placebo
Given PO
Other: laboratory biomarker analysis
Optional correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

I. 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:

I. Evaluate markers of bone turnover. (Exploratory)

OUTLINE: This is a multicenter study. Patients are stratified according to prior abiraterone or sipuleucel-T therapy (yes vs no). 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.

Patients may undergo serum and urine sample collection at baseline and periodically during treatment for biomarker studies.

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically documented adenocarcinoma of the prostate with progressive systemic disease (either rising PSA or progression of disease on computed tomography (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
  • 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
  • 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

Exclusion Criteria:

  • 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 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 2C19 (CYP2C19) and strong inhibitors of 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
  • 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: QTcF or 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 >= 1.5 times 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01519414

Locations
United States, District of Columbia
Lombardi Comprehensive Cancer Center at Georgetown University Recruiting
Washington, District of Columbia, United States, 20057
Contact: Nancy A. Dawson    202-444-9094    Nad103@gunet.georgetown.edu   
Principal Investigator: Nancy A. Dawson         
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute Recruiting
Tampa, Florida, United States, 33612
Contact: Shilpa Gupta    813-745-8418    Shilpa.gupta@moffitt.org   
Principal Investigator: Shilpa Gupta         
United States, Illinois
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Contact: Timothy M. Kuzel    312-695-4544    t-kuzel@northwestern.edu   
Principal Investigator: Timothy M. Kuzel         
University of Chicago Comprehensive Cancer Center Recruiting
Chicago, Illinois, United States, 60637-1470
Contact: Walter M. Stadler    773-702-4150    wstadler@medicine.bsd.uchicago.edu   
Principal Investigator: Walter M. Stadler         
Decatur Memorial Hospital Recruiting
Decatur, Illinois, United States, 62526
Contact: James L. Wade    217-876-6600    Jlwade3@sbcglobal.net   
Principal Investigator: James L. Wade         
Evanston CCOP-NorthShore University HealthSystem Recruiting
Evanston, Illinois, United States, 60201
Contact: Daniel H. Shevrin    847-570-2515    dshevrin@northshore.org   
Principal Investigator: Daniel H. Shevrin         
Ingalls Memorial Hospital Recruiting
Harvey, Illinois, United States, 60426
Contact: Mark F. Kozloff    708-339-4800    mfkozloff@aol.com   
Principal Investigator: Mark F. Kozloff         
Illinois CancerCare-Peoria Recruiting
Peoria, Illinois, United States, 61615
Contact: Sachdev P. Thomas    309-243-3605    sthomas@illinoiscancercare.com   
Principal Investigator: Sachdev P. Thomas         
Southern Illinois University Recruiting
Springfield, Illinois, United States, 62702
Contact: Krishna A. Rao    217-545-5817    krao@siumed.edu   
Principal Investigator: Krishna A. Rao         
United States, Indiana
Fort Wayne Medical Oncology and Hematology Inc - State Boulevard Recruiting
Fort Wayne, Indiana, United States, 46845
Contact: Sreenivasa R. Nattam    206-484-8830    ledger@fwmoh.com   
Principal Investigator: Sreenivasa R. Nattam         
Indiana University Medical Center Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Noah M. Hahn    317-278-6871    nhahn@iupui.edu   
Principal Investigator: Noah M. Hahn         
United States, Maryland
University of Maryland Greenebaum Cancer Center Recruiting
Baltimore, Maryland, United States, 21201-1595
Contact: Martin J. Edelman    410-328-2700    medelman@umm.edu   
Principal Investigator: Martin J. Edelman         
University of Maryland Saint Joseph Medical Center Recruiting
Towson, Maryland, United States, 21204
Contact: Richard Schrader    410-427-5585    richardschrader@catholichealth.net   
Principal Investigator: Richard Schrader         
United States, Missouri
Saint John's Mercy Medical Center Recruiting
Saint Louis, Missouri, United States, 63141
Contact: Bethany G. Sleckman    314-251-7057    slecbg@stlo.mercy.net   
Principal Investigator: Bethany G. Sleckman         
United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263
Contact: Roberto Pili    716-845-3851    Roberto.Pili@RoswellPark.org   
Principal Investigator: Roberto Pili         
United States, Ohio
Case Western Reserve University Recruiting
Cleveland, Ohio, United States, 44106
Contact: Matthew M. Cooney    216-844-3042    Matthew.cooney@uhhospitals.org   
Principal Investigator: Matthew M. Cooney         
Cleveland Clinic Foundation Recruiting
Cleveland, Ohio, United States, 44195
Contact: Jorge A. Garcia    216-444-7774    Garciaj4@ccf.org   
Principal Investigator: Jorge A. Garcia         
Ohio State University Medical Center Recruiting
Columbus, Ohio, United States, 43210
Contact: J. P. Monk    614-293-2886    Paul.Monk@osumc.edu   
Principal Investigator: J. P. Monk         
United States, Wisconsin
University of Wisconsin Hospital and Clinics Recruiting
Madison, Wisconsin, United States, 53792
Contact: Glenn Liu    608-263-7107    gxl@medicine.wisc.edu   
Principal Investigator: Glenn Liu         
Sponsors and Collaborators
Investigators
Principal Investigator: J. Monk Ohio State University
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01519414     History of Changes
Other Study ID Numbers: NCI-2012-00237, NCI-2012-00237, CDR0000721410, OSU11132, OSU-11132, OSU 11132, 8986, N01CM00070, U01CA062491, P30CA016058, N01CM00071, N01CM00100
Study First Received: January 25, 2012
Last Updated: October 7, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Prostatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases

ClinicalTrials.gov processed this record on April 17, 2014