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Tivantinib in Treating Patients With Metastatic Prostate Cancer

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Completed
CT.gov ID
NCT01519414
Collaborator
(none)
78
Enrollment
20
Locations
2
Arms
43.2
Actual Duration (Months)
3.9
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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.

  2. 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.

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

  4. 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.

Study Design

Study Type:
Interventional
Actual Enrollment :
78 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
Double (Participant, 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
Actual Study Start Date :
Jan 11, 2012
Actual Primary Completion Date :
Aug 18, 2015
Actual Study Completion Date :
Aug 18, 2015

Arms and Interventions

Arm Intervention/Treatment
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.

Other: Laboratory Biomarker Analysis
Optional correlative studies

Drug: Tivantinib
Given PO
Other Names:
  • ARQ 197
  • ARQ-197
  • c-Met Inhibitor ARQ 197

    		•
    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: Laboratory Biomarker Analysis
    Optional correlative studies

    Other: Placebo
    Given PO
    Other Names:
  • placebo therapy
  • PLCB
  • sham therapy

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Progression-free Survival (PFS) Based on the RECIST Criteria [Time from study entry to the date of documented progression and/or death, assessed up to 6 months]

      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

    1. Changes in PSA Levels [Baseline to 12 weeks]

      Evaluated and patterns graphically explored through waterfall plots.

    2. Proportion of Patients Who Respond [At 12 weeks]

      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.

    3. PSA Response Rate [up to 12 weeks]

      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.

    4. Incidence of Adverse Events Graded as 3, 4, or 5 Per NCI CTCAE Version 4.0 [Up to 1 year]

      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

    1. Radiographic Response Rate Based on RECIST Criteria [Up to 12 weeks]

      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.

    2. Change in Bone Specific Alkaline Phosphatase (BSAP) in Serum [Baseline to up to 6 months]

      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.

    3. Change in Markers of Bone Turnover in Urine [Baseline to up to 6 months]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    No
    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

    Locations

    Site City State Country Postal Code
    1 MedStar Georgetown University Hospital Washington District of Columbia United States 20007
    2 Moffitt Cancer Center Tampa Florida United States 33612
    3 Northwestern University Chicago Illinois United States 60611
    4 Michael Reese Hospital Chicago Illinois United States 60616
    5 University of Chicago Comprehensive Cancer Center Chicago Illinois United States 60637
    6 Decatur Memorial Hospital Decatur Illinois United States 62526
    7 NorthShore University HealthSystem-Evanston Hospital Evanston Illinois United States 60201
    8 Ingalls Memorial Hospital Harvey Illinois United States 60426
    9 Illinois CancerCare-Peoria Peoria Illinois United States 61615
    10 Southern Illinois University School of Medicine Springfield Illinois United States 62702
    11 Fort Wayne Medical Oncology and Hematology Inc - Jefferson Boulevard Fort Wayne Indiana United States 46804
    12 Indiana University/Melvin and Bren Simon Cancer Center Indianapolis Indiana United States 46202
    13 University of Maryland/Greenebaum Cancer Center Baltimore Maryland United States 21201
    14 University of Maryland Saint Joseph Medical Center Towson Maryland United States 21204
    15 Mercy Hospital Saint Louis Saint Louis Missouri United States 63141
    16 Roswell Park Cancer Institute Buffalo New York United States 14263
    17 Case Western Reserve University Cleveland Ohio United States 44106
    18 Cleveland Clinic Foundation Cleveland Ohio United States 44195
    19 Ohio State University Comprehensive Cancer Center Columbus Ohio United States 43210
    20 University of Wisconsin Hospital and Clinics Madison Wisconsin United States 53792

    Sponsors and Collaborators

    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: J. Monk, Ohio State University Comprehensive Cancer Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT01519414
    Other Study ID Numbers:
    • NCI-2012-00237
    • NCI-2012-00237
    • CDR0000721410
    • OSU11132
    • OSU-11132
    • OSU 11132
    • 8986
    • N01CM00070
    • N01CM00071
    • N01CM00100
    • N01CM62207
    • P30CA016058
    • U01CA062491
    First Posted:
    Jan 27, 2012
    Last Update Posted:
    Sep 12, 2018
    Last Verified:
    Aug 1, 2018
    Additional relevant MeSH terms:
    Prostatic Neoplasms

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Arm I (Tivantinib) Arm II (Placebo) Crossover From Placebo to Tivantinib
    Arm/Group Description Patients receive tivantinib 360 mg (3 * 120 mg tablets) po BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive matched placebo (3 tablets) 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 who were originally assigned to placebo and experience disease progression will be allowed to crossover and take ARQ 197. The treatment plan, duration of therapy, criteria for progression and follow-up will be the same as described above for men originally assigned to ARQ 197.
    Period Title: Pre Cross-over
    STARTED 52 26 0
    COMPLETED 52 26 0
    NOT COMPLETED 0 0 0
    Period Title: Pre Cross-over
    STARTED 52 14 12
    COMPLETED 52 14 12
    NOT COMPLETED 0 0 0

    Baseline Characteristics

    Arm/Group Title Arm I (Tivantinib) Arm II (Placebo) Total
    Arm/Group Description Patients receive tivantinib 360 mg (3 * 120 mg tablets) po BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive matched placebo (3 tablets) 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. Total of all reporting groups
    Overall Participants 52 26 78
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    67
    66.5
    67
    Sex: Female, Male (Count of Participants)
    Female
    0
    0%
    0
    0%
    0
    0%
    Male
    52
    100%
    26
    100%
    78
    100%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    1
    1.9%
    0
    0%
    1
    1.3%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    2
    3.8%
    6
    23.1%
    8
    10.3%
    White
    49
    94.2%
    20
    76.9%
    69
    88.5%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (patients) [Number]
    United States
    52
    26
    78

    Outcome Measures

    1. Primary Outcome
    Title Progression-free Survival (PFS) Based on the RECIST Criteria
    Description 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 Frame Time from study entry to the date of documented progression and/or death, assessed up to 6 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm I (Tivantinib) Arm II (Placebo)
    Arm/Group Description Patients receive tivantinib 360 mg (3 * 120 mg tablets) po BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive matched placebo (3 tablets) 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.
    Measure Participants 52 26
    Median (95% Confidence Interval) [months]
    5.5
    3.7
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm I (Tivantinib), Arm II (Placebo)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.02
    Comments
    Method Log Rank
    Comments
    2. Secondary Outcome
    Title Changes in PSA Levels
    Description Evaluated and patterns graphically explored through waterfall plots.
    Time Frame Baseline to 12 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm I (Tivantinib) Arm II (Placebo)
    Arm/Group Description Patients receive tivantinib 360 mg (3 * 120 mg tablets) po BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive matched placebo (3 tablets) 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.
    Measure Participants 52 26
    Median (Full Range) [percentage change from baseline]
    140.1
    301.5
    3. Secondary Outcome
    Title Proportion of Patients Who Respond
    Description 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.
    Time Frame At 12 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm I (Tivantinib) Arm II (Placebo) Crossover From Placebo to Tivantinib
    Arm/Group Description Arm I: Patients receive tivantinib 360 mg (3 * 120 mg tablets) po BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. 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 Patients who were originally assigned to placebo and experience disease progression will be allowed to crossover and take ARQ 197. The treatment plan, duration of therapy, criteria for progression and follow-up will be the same as described above for men originally assigned to ARQ 197.
    Measure Participants 52 26 12
    Number (95% Confidence Interval) [percentage of patients]
    1.9
    0
    8.3
    4. Secondary Outcome
    Title PSA Response Rate
    Description 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.
    Time Frame up to 12 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm I (Tivantinib) Arm II (Placebo) Crossover From Placebo to Tivantinib
    Arm/Group Description Patients receive tivantinib 360 mg (3 * 120 mg tablets) po BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive matched placebo (3 tablets) 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 who were originally assigned to placebo and experience disease progression will be allowed to crossover and take ARQ 197. The treatment plan, duration of therapy, criteria for progression and follow-up will be the same as described above for men originally assigned to ARQ 197.
    Measure Participants 52 26 12
    Number (95% Confidence Interval) [percentage of patients]
    1.9
    0
    8.3
    5. Secondary Outcome
    Title Incidence of Adverse Events Graded as 3, 4, or 5 Per NCI CTCAE Version 4.0
    Description 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.
    Time Frame Up to 1 year

    Outcome Measure Data

    Analysis Population Description
    Adverse events graded as 3, 4 or 5 per NCI CTCAE version 4 (regardless of attribution)
    Arm/Group Title Arm I (Tivantinib) Arm II (Placebo) Crossover From Placebo to Tivantinib
    Arm/Group Description Patients receive tivantinib 360 mg (3 * 120 mg tablets) po BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive matched placebo (3 tablets) 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 who were originally assigned to placebo and experience disease progression will be allowed to crossover and take ARQ 197. The treatment plan, duration of therapy, criteria for progression and follow-up will be the same as described above for men originally assigned to ARQ 197.
    Measure Participants 52 26 12
    Acute coronary syndrome
    1
    0
    0
    Alkaline phosphatase increased
    0
    0
    2
    Anemia
    3
    0
    2
    Back pain
    1
    1
    1
    Confusion
    0
    2
    0
    Cataract
    1
    0
    0
    Death NOS
    1
    0
    1
    Dehydration
    0
    2
    1
    Dizziness
    0
    1
    0
    Duodenal ulcer
    1
    0
    0
    Dyspnea
    0
    1
    0
    Enterocolitis infectious
    0
    1
    0
    Fall
    0
    1
    0
    Fatigue
    2
    0
    0
    Febrile neutropenia
    1
    0
    0
    Gait disturbance
    0
    1
    0
    Generalized muscle weakness
    0
    1
    0
    Hypertension
    1
    0
    0
    Hypokalemia
    0
    1
    0
    Hyponatremia
    1
    0
    0
    Hypotension
    0
    1
    0
    Hypoxia
    1
    1
    0
    Infections and infestations - Other, specify
    1
    0
    0
    Lymph gland infection
    1
    0
    0
    Lymphocyte count decreased
    2
    2
    2
    Musculoskeletal and connective tissue disorder - O
    0
    1
    0
    Neoplasms benign, malignant and unspecified (incl
    1
    1
    0
    Nervous system disorders - Other, specify
    0
    1
    0
    Neutrophil count decreased
    2
    0
    2
    Platelet count decreased
    1
    0
    0
    Pleural effusion
    0
    0
    1
    Productive cough
    0
    0
    1
    Sinus bradycardia
    3
    0
    0
    Sinus tachycardia
    0
    1
    0
    Syncope
    0
    2
    0
    Thromboembolic event
    0
    1
    0
    Tumor pain
    1
    0
    0
    Upper respiratory infection
    0
    1
    0
    Urinary tract obstruction
    0
    0
    1
    White blood cell decreased
    2
    0
    2
    6. Other Pre-specified Outcome
    Title Radiographic Response Rate Based on RECIST Criteria
    Description 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.
    Time Frame Up to 12 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm I (Tivantinib) Arm II (Placebo) Crossover From Placebo to Tivantinib
    Arm/Group Description Arm I: Patients receive tivantinib 360 mg (3 * 120 mg tablets) po BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive matched placebo (3 tablets) 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 who were originally assigned to placebo and experience disease progression will be allowed to crossover and take ARQ 197. The treatment plan, duration of therapy, criteria for progression and follow-up will be the same as described above for men originally assigned to ARQ 197.
    Measure Participants 52 26 12
    Number (95% Confidence Interval) [percentage of patients]
    1.9
    0
    8.3
    7. Other Pre-specified Outcome
    Title Change in Bone Specific Alkaline Phosphatase (BSAP) in Serum
    Description 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.
    Time Frame Baseline to up to 6 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    8. Other Pre-specified Outcome
    Title Change in Markers of Bone Turnover in Urine
    Description 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.
    Time Frame Baseline to up to 6 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description

    Adverse Events

    Time Frame
    Adverse Event Reporting Description The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.
    Arm/Group Title Arm I (Tivantinib) Arm II (Placebo) Crossover From Placebo to Tivantinib
    Arm/Group Description Patients receive tivantinib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. 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 who were originally assigned to placebo and experience disease progression will be allowed to crossover and take ARQ 197. The treatment plan, duration of therapy, criteria for progression and follow-up will be the same as described above for men originally assigned to ARQ 197.
    All Cause Mortality
    Arm I (Tivantinib) Arm II (Placebo) Crossover From Placebo to Tivantinib
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 7/52 (13.5%) 4/26 (15.4%) 0/12 (0%)
    Serious Adverse Events
    Arm I (Tivantinib) Arm II (Placebo) Crossover From Placebo to Tivantinib
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 19/52 (36.5%) 22/26 (84.6%) 5/12 (41.7%)
    Blood and lymphatic system disorders
    Anemia 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Cardiac disorders
    Acute coronary syndrome 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Sinus bradycardia 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Sinus tachycardia 0/52 (0%) 0 1/26 (3.8%) 1 0/12 (0%) 0
    Gastrointestinal disorders
    Abdominal pain 0/52 (0%) 0 1/26 (3.8%) 1 0/12 (0%) 0
    Constipation 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Diarrhea 0/52 (0%) 0 1/26 (3.8%) 1 0/12 (0%) 0
    Duodenal ulcer 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Nausea 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    General disorders
    Death NOS 1/52 (1.9%) 1 0/26 (0%) 0 1/12 (8.3%) 1
    Edema limbs 1/52 (1.9%) 1 0/26 (0%) 0 1/12 (8.3%) 1
    Fatigue 1/52 (1.9%) 1 0/26 (0%) 0 1/12 (8.3%) 1
    Fever 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Gait disturbance 0/52 (0%) 0 1/26 (3.8%) 1 0/12 (0%) 0
    Infections and infestations
    Enterocolitis infectious 0/52 (0%) 0 1/26 (3.8%) 1 0/12 (0%) 0
    Infections and infestations - Other, specify 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Upper respiratory infection 0/52 (0%) 0 1/26 (3.8%) 1 0/12 (0%) 0
    Injury, poisoning and procedural complications
    Fall 0/52 (0%) 0 1/26 (3.8%) 1 0/12 (0%) 0
    Metabolism and nutrition disorders
    Anorexia 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Dehydration 0/52 (0%) 0 2/26 (7.7%) 2 0/12 (0%) 0
    Musculoskeletal and connective tissue disorders
    Generalized muscle weakness 1/52 (1.9%) 1 1/26 (3.8%) 1 0/12 (0%) 0
    Musculoskeletal and connective tissue disorder - Other, specify 0/52 (0%) 0 1/26 (3.8%) 1 0/12 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify 1/52 (1.9%) 1 1/26 (3.8%) 1 0/12 (0%) 0
    Tumor pain 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Nervous system disorders
    Dizziness 0/52 (0%) 0 1/26 (3.8%) 1 0/12 (0%) 0
    Nervous system disorders - Other, specify 0/52 (0%) 0 1/26 (3.8%) 1 0/12 (0%) 0
    Seizure 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Stroke 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Syncope 0/52 (0%) 0 1/26 (3.8%) 1 0/12 (0%) 0
    Psychiatric disorders
    Confusion 0/52 (0%) 0 2/26 (7.7%) 2 0/12 (0%) 0
    Renal and urinary disorders
    Urinary tract obstruction 0/52 (0%) 0 0/26 (0%) 0 1/12 (8.3%) 1
    Respiratory, thoracic and mediastinal disorders
    Dyspnea 0/52 (0%) 0 1/26 (3.8%) 1 0/12 (0%) 0
    Hypoxia 1/52 (1.9%) 1 1/26 (3.8%) 1 0/12 (0%) 0
    Pleural effusion 0/52 (0%) 0 0/26 (0%) 0 1/12 (8.3%) 1
    Vascular disorders
    Hypotension 0/52 (0%) 0 1/26 (3.8%) 1 0/12 (0%) 0
    Thromboembolic event 1/52 (1.9%) 1 2/26 (7.7%) 2 0/12 (0%) 0
    Other (Not Including Serious) Adverse Events
    Arm I (Tivantinib) Arm II (Placebo) Crossover From Placebo to Tivantinib
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 52/52 (100%) 26/26 (100%) 12/12 (100%)
    Blood and lymphatic system disorders
    Anemia 23/52 (44.2%) 23 12/26 (46.2%) 12 6/12 (50%) 6
    Febrile neutropenia 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Lymph node pain 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Cardiac disorders
    Atrial fibrillation 0/52 (0%) 0 1/26 (3.8%) 1 0/12 (0%) 0
    Cardiac disorders - Other, specify 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Sinus bradycardia 11/52 (21.2%) 11 1/26 (3.8%) 1 1/12 (8.3%) 1
    Sinus tachycardia 0/52 (0%) 0 1/26 (3.8%) 1 0/12 (0%) 0
    Ear and labyrinth disorders
    Ear pain 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Endocrine disorders
    Hypothyroidism 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Eye disorders
    Blurred vision 2/52 (3.8%) 2 3/26 (11.5%) 3 1/12 (8.3%) 1
    Cataract 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Eye disorders - Other, specify 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Eye pain 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Flashing lights 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Gastrointestinal disorders
    Abdominal pain 1/52 (1.9%) 1 3/26 (11.5%) 3 1/12 (8.3%) 1
    Bloating 0/52 (0%) 0 1/26 (3.8%) 1 0/12 (0%) 0
    Colonic hemorrhage 0/52 (0%) 0 1/26 (3.8%) 1 0/12 (0%) 0
    Constipation 14/52 (26.9%) 14 7/26 (26.9%) 7 3/12 (25%) 3
    Diarrhea 8/52 (15.4%) 8 4/26 (15.4%) 4 3/12 (25%) 3
    Dry mouth 2/52 (3.8%) 2 4/26 (15.4%) 4 0/12 (0%) 0
    Dyspepsia 2/52 (3.8%) 2 2/26 (7.7%) 2 1/12 (8.3%) 1
    Dysphagia 1/52 (1.9%) 1 0/26 (0%) 0 1/12 (8.3%) 1
    Fecal incontinence 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Flatulence 2/52 (3.8%) 2 2/26 (7.7%) 2 0/12 (0%) 0
    Gastric hemorrhage 0/52 (0%) 0 1/26 (3.8%) 1 0/12 (0%) 0
    Gastroesophageal reflux disease 1/52 (1.9%) 1 1/26 (3.8%) 1 0/12 (0%) 0
    Gastrointestinal disorders - Other, specify 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Hemorrhoidal hemorrhage 2/52 (3.8%) 2 0/26 (0%) 0 0/12 (0%) 0
    Hemorrhoids 4/52 (7.7%) 4 1/26 (3.8%) 1 0/12 (0%) 0
    Mucositis oral 0/52 (0%) 0 1/26 (3.8%) 1 0/12 (0%) 0
    Nausea 9/52 (17.3%) 9 5/26 (19.2%) 5 3/12 (25%) 3
    Oral dysesthesia 0/52 (0%) 0 1/26 (3.8%) 1 0/12 (0%) 0
    Oral pain 2/52 (3.8%) 2 2/26 (7.7%) 2 1/12 (8.3%) 1
    Rectal hemorrhage 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Rectal pain 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Stomach pain 0/52 (0%) 0 1/26 (3.8%) 1 0/12 (0%) 0
    Toothache 0/52 (0%) 0 1/26 (3.8%) 1 0/12 (0%) 0
    Vomiting 4/52 (7.7%) 4 2/26 (7.7%) 2 1/12 (8.3%) 1
    General disorders
    Chills 0/52 (0%) 0 1/26 (3.8%) 1 2/12 (16.7%) 2
    Edema face 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Edema limbs 5/52 (9.6%) 5 2/26 (7.7%) 2 1/12 (8.3%) 1
    Edema trunk 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Facial pain 2/52 (3.8%) 2 0/26 (0%) 0 0/12 (0%) 0
    Fatigue 30/52 (57.7%) 30 11/26 (42.3%) 11 7/12 (58.3%) 7
    Fever 1/52 (1.9%) 1 1/26 (3.8%) 1 1/12 (8.3%) 1
    Flu like symptoms 1/52 (1.9%) 1 0/26 (0%) 0 1/12 (8.3%) 1
    General disorders and administration site conditions - Other, specify 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Irritability 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Localized edema 2/52 (3.8%) 2 2/26 (7.7%) 2 0/12 (0%) 0
    Malaise 2/52 (3.8%) 2 0/26 (0%) 0 0/12 (0%) 0
    Neck edema 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Non-cardiac chest pain 1/52 (1.9%) 1 1/26 (3.8%) 1 0/12 (0%) 0
    Pain 5/52 (9.6%) 5 7/26 (26.9%) 7 2/12 (16.7%) 2
    Infections and infestations
    Conjunctivitis infective 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Infections and infestations - Other, specify 0/52 (0%) 0 1/26 (3.8%) 1 0/12 (0%) 0
    Lung infection 0/52 (0%) 0 0/26 (0%) 0 1/12 (8.3%) 1
    Lymph gland infection 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Papulopustular rash 0/52 (0%) 0 1/26 (3.8%) 1 0/12 (0%) 0
    Rhinitis infective 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Sinusitis 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Upper respiratory infection 3/52 (5.8%) 3 2/26 (7.7%) 2 0/12 (0%) 0
    Urinary tract infection 2/52 (3.8%) 2 1/26 (3.8%) 1 1/12 (8.3%) 1
    Injury, poisoning and procedural complications
    Bruising 0/52 (0%) 0 1/26 (3.8%) 1 1/12 (8.3%) 1
    Burn 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Fracture 1/52 (1.9%) 1 0/26 (0%) 0 1/12 (8.3%) 1
    Investigations
    Alanine aminotransferase increased 7/52 (13.5%) 7 2/26 (7.7%) 2 0/12 (0%) 0
    Alkaline phosphatase increased 8/52 (15.4%) 8 5/26 (19.2%) 5 3/12 (25%) 3
    Aspartate aminotransferase increased 13/52 (25%) 13 3/26 (11.5%) 3 2/12 (16.7%) 2
    Creatinine increased 7/52 (13.5%) 7 1/26 (3.8%) 1 1/12 (8.3%) 1
    Lymphocyte count decreased 11/52 (21.2%) 11 6/26 (23.1%) 6 4/12 (33.3%) 4
    Lymphocyte count increased 0/52 (0%) 0 1/26 (3.8%) 1 0/12 (0%) 0
    Neutrophil count decreased 5/52 (9.6%) 5 0/26 (0%) 0 5/12 (41.7%) 5
    Platelet count decreased 3/52 (5.8%) 3 2/26 (7.7%) 2 1/12 (8.3%) 1
    Weight gain 2/52 (3.8%) 2 0/26 (0%) 0 0/12 (0%) 0
    Weight loss 4/52 (7.7%) 4 1/26 (3.8%) 1 0/12 (0%) 0
    White blood cell decreased 12/52 (23.1%) 12 1/26 (3.8%) 1 5/12 (41.7%) 5
    Metabolism and nutrition disorders
    Anorexia 17/52 (32.7%) 17 5/26 (19.2%) 5 6/12 (50%) 6
    Dehydration 1/52 (1.9%) 1 0/26 (0%) 0 1/12 (8.3%) 1
    Hypercalcemia 0/52 (0%) 0 1/26 (3.8%) 1 0/12 (0%) 0
    Hyperglycemia 9/52 (17.3%) 9 3/26 (11.5%) 3 1/12 (8.3%) 1
    Hyperkalemia 5/52 (9.6%) 5 0/26 (0%) 0 0/12 (0%) 0
    Hypoalbuminemia 4/52 (7.7%) 4 2/26 (7.7%) 2 1/12 (8.3%) 1
    Hypocalcemia 4/52 (7.7%) 4 1/26 (3.8%) 1 3/12 (25%) 3
    Hypokalemia 3/52 (5.8%) 3 2/26 (7.7%) 2 3/12 (25%) 3
    Hyponatremia 11/52 (21.2%) 11 3/26 (11.5%) 3 3/12 (25%) 3
    Metabolism and nutrition disorders - Other, specify 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/52 (1.9%) 1 1/26 (3.8%) 1 0/12 (0%) 0
    Back pain 9/52 (17.3%) 9 13/26 (50%) 13 3/12 (25%) 3
    Bone pain 3/52 (5.8%) 3 1/26 (3.8%) 1 1/12 (8.3%) 1
    Chest wall pain 1/52 (1.9%) 1 0/26 (0%) 0 1/12 (8.3%) 1
    Flank pain 3/52 (5.8%) 3 2/26 (7.7%) 2 1/12 (8.3%) 1
    Generalized muscle weakness 3/52 (5.8%) 3 3/26 (11.5%) 3 1/12 (8.3%) 1
    Muscle weakness lower limb 3/52 (5.8%) 3 3/26 (11.5%) 3 1/12 (8.3%) 1
    Muscle weakness upper limb 1/52 (1.9%) 1 0/26 (0%) 0 1/12 (8.3%) 1
    Musculoskeletal and connective tissue disorder - Other, specify 0/52 (0%) 0 0/26 (0%) 0 1/12 (8.3%) 1
    Myalgia 2/52 (3.8%) 2 1/26 (3.8%) 1 0/12 (0%) 0
    Pain in extremity 13/52 (25%) 13 11/26 (42.3%) 11 2/12 (16.7%) 2
    Trismus 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Nervous system disorders
    Dizziness 5/52 (9.6%) 5 1/26 (3.8%) 1 1/12 (8.3%) 1
    Dysgeusia 5/52 (9.6%) 5 2/26 (7.7%) 2 1/12 (8.3%) 1
    Headache 1/52 (1.9%) 1 2/26 (7.7%) 2 2/12 (16.7%) 2
    Ischemia cerebrovascular 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Memory impairment 1/52 (1.9%) 1 1/26 (3.8%) 1 0/12 (0%) 0
    Paresthesia 0/52 (0%) 0 2/26 (7.7%) 2 0/12 (0%) 0
    Peripheral motor neuropathy 2/52 (3.8%) 2 1/26 (3.8%) 1 0/12 (0%) 0
    Peripheral sensory neuropathy 2/52 (3.8%) 2 4/26 (15.4%) 4 1/12 (8.3%) 1
    Sinus pain 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Syncope 0/52 (0%) 0 1/26 (3.8%) 1 0/12 (0%) 0
    Tremor 1/52 (1.9%) 1 0/26 (0%) 0 1/12 (8.3%) 1
    Psychiatric disorders
    Anxiety 4/52 (7.7%) 4 2/26 (7.7%) 2 0/12 (0%) 0
    Depression 1/52 (1.9%) 1 3/26 (11.5%) 3 0/12 (0%) 0
    Insomnia 2/52 (3.8%) 2 1/26 (3.8%) 1 1/12 (8.3%) 1
    Renal and urinary disorders
    Hematuria 4/52 (7.7%) 4 0/26 (0%) 0 0/12 (0%) 0
    Proteinuria 2/52 (3.8%) 2 0/26 (0%) 0 0/12 (0%) 0
    Renal and urinary disorders - Other, specify 1/52 (1.9%) 1 0/26 (0%) 0 1/12 (8.3%) 1
    Urinary frequency 3/52 (5.8%) 3 4/26 (15.4%) 4 0/12 (0%) 0
    Urinary incontinence 3/52 (5.8%) 3 0/26 (0%) 0 1/12 (8.3%) 1
    Urinary retention 1/52 (1.9%) 1 1/26 (3.8%) 1 0/12 (0%) 0
    Urinary tract pain 1/52 (1.9%) 1 1/26 (3.8%) 1 2/12 (16.7%) 2
    Urinary urgency 2/52 (3.8%) 2 0/26 (0%) 0 1/12 (8.3%) 1
    Reproductive system and breast disorders
    Breast pain 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Erectile dysfunction 0/52 (0%) 0 0/26 (0%) 0 1/12 (8.3%) 1
    Genital edema 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Pelvic pain 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Penile pain 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Scrotal pain 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Allergic rhinitis 1/52 (1.9%) 1 0/26 (0%) 0 1/12 (8.3%) 1
    Cough 9/52 (17.3%) 9 2/26 (7.7%) 2 1/12 (8.3%) 1
    Dyspnea 8/52 (15.4%) 8 0/26 (0%) 0 2/12 (16.7%) 2
    Epistaxis 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Hoarseness 1/52 (1.9%) 1 1/26 (3.8%) 1 0/12 (0%) 0
    Laryngeal mucositis 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Nasal congestion 2/52 (3.8%) 2 2/26 (7.7%) 2 1/12 (8.3%) 1
    Postnasal drip 2/52 (3.8%) 2 0/26 (0%) 0 0/12 (0%) 0
    Productive cough 0/52 (0%) 0 1/26 (3.8%) 1 1/12 (8.3%) 1
    Respiratory, thoracic and mediastinal disorders - Other, specify 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Sinus disorder 1/52 (1.9%) 1 0/26 (0%) 0 1/12 (8.3%) 1
    Sore throat 3/52 (5.8%) 3 0/26 (0%) 0 0/12 (0%) 0
    Skin and subcutaneous tissue disorders
    Alopecia 7/52 (13.5%) 7 2/26 (7.7%) 2 3/12 (25%) 3
    Dry skin 2/52 (3.8%) 2 1/26 (3.8%) 1 0/12 (0%) 0
    Erythema multiforme 2/52 (3.8%) 2 0/26 (0%) 0 0/12 (0%) 0
    Hypertrichosis 0/52 (0%) 0 0/26 (0%) 0 1/12 (8.3%) 1
    Nail ridging 2/52 (3.8%) 2 0/26 (0%) 0 0/12 (0%) 0
    Periorbital edema 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Pruritus 3/52 (5.8%) 3 3/26 (11.5%) 3 0/12 (0%) 0
    Rash acneiform 2/52 (3.8%) 2 1/26 (3.8%) 1 0/12 (0%) 0
    Rash maculo-papular 5/52 (9.6%) 5 2/26 (7.7%) 2 0/12 (0%) 0
    Skin and subcutaneous tissue disorders - Other, specify 1/52 (1.9%) 1 1/26 (3.8%) 1 0/12 (0%) 0
    Skin ulceration 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Urticaria 0/52 (0%) 0 2/26 (7.7%) 2 0/12 (0%) 0
    Vascular disorders
    Hot flashes 5/52 (9.6%) 5 2/26 (7.7%) 2 0/12 (0%) 0
    Hypertension 5/52 (9.6%) 5 2/26 (7.7%) 2 0/12 (0%) 0
    Hypotension 1/52 (1.9%) 1 0/26 (0%) 0 2/12 (16.7%) 2
    Lymphedema 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0
    Thromboembolic event 1/52 (1.9%) 1 0/26 (0%) 0 0/12 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Paul Monk, MD
    Organization The Ohio State University Comprehensive Cancer Center
    Phone (614) 293-6196
    Email Paul.Monk@osumc.edu
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT01519414
    Other Study ID Numbers:
    • NCI-2012-00237
    • NCI-2012-00237
    • CDR0000721410
    • OSU11132
    • OSU-11132
    • OSU 11132
    • 8986
    • N01CM00070
    • N01CM00071
    • N01CM00100
    • N01CM62207
    • P30CA016058
    • U01CA062491
    First Posted:
    Jan 27, 2012
    Last Update Posted:
    Sep 12, 2018
    Last Verified:
    Aug 1, 2018