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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01519414
First received: January 25, 2012
Last updated: November 25, 2014
Last verified: July 2014
  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
Hormone-Resistant Prostate Cancer
Prostate Adenocarcinoma
Recurrent Prostate Carcinoma
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: At 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: At 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 adverse events graded as 3, 4, or 5 per NCI CTCAE version 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.


Other Outcome Measures:
  • Change in markers of bone turnover in urine [ Time Frame: Baseline to up to 6 months ] [ Designated as safety issue: No ]
    NTx and CTX will first be descriptively summarized by treatment group and also evaluated using graphical analyses to assess potential patterns over time and see if changes in bone resorption differ between those who are progression-free at 12 weeks vs. not after treatment with tivantinib. The potential impact of early changes in these markers on PFS using Cox regression models will be also explored.

  • Change in bone specific alkaline phosphatase (BSAP) in serum [ Time Frame: Baseline to up to 6 months ] [ Designated as safety issue: No ]
    BSAP will first be descriptively summarized by treatment group and also evaluated using graphical analyses to assess potential patterns over time and see if changes in bone resorption differ between those who are progression-free at 12 weeks vs. not after treatment with tivantinib. The potential impact of early changes in these markers on PFS using Cox regression models will be also explored.


Estimated Enrollment: 78
Study Start Date: January 2012
Estimated Primary Completion Date: July 2015 (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 Names:
  • ARQ 197
  • ARQ-197
  • c-Met Inhibitor ARQ 197
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 Name: PLCB
Other: Laboratory Biomarker Analysis
Optional correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. 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:

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: 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.

  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 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; 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

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 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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01519414

Locations
United States, District of Columbia
Lombardi Comprehensive Cancer Center at Georgetown University
Washington, District of Columbia, United States, 20057
United States, Florida
Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Illinois
Michael Reese Hospital
Chicago, Illinois, United States, 60616
Northwestern University
Chicago, Illinois, United States, 60611
University of Chicago
Chicago, Illinois, United States, 60637
Decatur Memorial Hospital
Decatur, Illinois, United States, 62526
NorthShore University HealthSystem-Evanston Hospital
Evanston, Illinois, United States, 60201
Ingalls Memorial Hospital
Harvey, Illinois, United States, 60426
Illinois CancerCare-Peoria
Peoria, Illinois, United States, 61615
Southern Illinois University
Springfield, Illinois, United States, 62702
United States, Indiana
Fort Wayne Medical Oncology and Hematology Inc - Jefferson Boulevard
Fort Wayne, Indiana, United States, 46804
Indiana University Medical Center
Indianapolis, Indiana, United States, 46202
United States, Maryland
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, United States, 21201
University of Maryland Saint Joseph Medical Center
Towson, Maryland, United States, 21204
United States, Missouri
Saint John's Mercy Medical Center
Saint Louis, Missouri, United States, 63141
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
United States, Ohio
Case Western Reserve University
Cleveland, Ohio, United States, 44106
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
Ohio State University Medical Center
Columbus, Ohio, United States, 43210
United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792
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, N01CM00071, P30CA016058, N01CM62207, U01CA062491, N01CM00100, N01CM00070
Study First Received: January 25, 2012
Last Updated: November 25, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on November 25, 2014