Tivantinib in Treating Patients With Metastatic Prostate Cancer

NCT01519414 | Completed Phase 2 Results

• 12 other identifiers: NCI-2012-00237CDR0000721410OSU11132OSU-11132OSU 111328986N01CM00070N01CM00071N01CM00100N01CM62207P30CA016058U01CA062491
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 20

Brief 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.

Conditions

Hormone-Resistant Prostate Cancer; Prostate Adenocarcinoma; Recurrent Prostate Carcinoma; Stage IV Prostate Cancer

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (4)

• Changes in PSA Levels

  Baseline to 12 weeks

• Proportion of Patients Who Respond

  At 12 weeks

• PSA Response Rate

  up to 12 weeks

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

  Up to 1 year

Other Outcomes (3)

• Radiographic Response Rate Based on RECIST Criteria

  Up to 12 weeks

• Change in Bone Specific Alkaline Phosphatase (BSAP) in Serum

  Baseline to up to 6 months

• Change in Markers of Bone Turnover in Urine

  Baseline to up to 6 months

Study Arms (2)

Arm I (tivantinib)

EXPERIMENTAL

Patients receive tivantinib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Drug: Tivantinib

Arm II (placebo)

PLACEBO COMPARATOR

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: Laboratory Biomarker Analysis; Other: Placebo

Interventions

Laboratory Biomarker Analysis OTHER

Optional correlative studies

Arm I (tivantinib); Arm II (placebo)

Placebo OTHER

Given PO

Also known as: placebo therapy, PLCB, sham therapy

Arm II (placebo)

Tivantinib DRUG

Given PO

Also known as: ARQ 197, ARQ-197, c-Met Inhibitor ARQ 197

Arm I (tivantinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (20)

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Michael Reese Hospital

Chicago, Illinois, 60616, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Decatur Memorial Hospital

Decatur, Illinois, 62526, United States

Location

NorthShore University HealthSystem-Evanston Hospital

Evanston, Illinois, 60201, United States

Location

Ingalls Memorial Hospital

Harvey, Illinois, 60426, United States

Location

Illinois CancerCare-Peoria

Peoria, Illinois, 61615, United States

Location

Southern Illinois University School of Medicine

Springfield, Illinois, 62702, United States

Location

Fort Wayne Medical Oncology and Hematology Inc - Jefferson Boulevard

Fort Wayne, Indiana, 46804, United States

Location

Indiana University/Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

University of Maryland Saint Joseph Medical Center

Towson, Maryland, 21204, United States

Location

Mercy Hospital Saint Louis

St Louis, Missouri, 63141, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

ARQ 197

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Paul Monk, MD
• Organization: The Ohio State University Comprehensive Cancer Center

Paul.Monk@osumc.edu

(614) 293-6196

Study Officials

• J. Monk

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2012
• First Posted: January 27, 2012
• Study Start: January 11, 2012
• Primary Completion: August 18, 2015
• Study Completion: August 18, 2015
• Last Updated: September 12, 2018
• Results First Posted: September 12, 2018

Record last verified: 2018-08

Locations

US (20)