Phase I of Histone Deacetylase (HDAC) Inhibitor Panobinostat With Ipilimumab With Unresectable III/IV Melanoma

Sponsor
H. Lee Moffitt Cancer Center and Research Institute (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT02032810
Collaborator
Novartis (Industry)
17
Enrollment
1
Location
1
Arm
98.8
Anticipated Duration (Months)
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to find out if an investigational drug called panobinostat can be given safely with another drug called ipilimumab. Investigators want to learn more about the side effects of this combination of drugs using different doses of panobinostat and the same dose of ipilimumab.

Condition or DiseaseIntervention/TreatmentPhase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
17 participants
Allocation:
N/A
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1 Study of HDAC Inhibitor Panobinostat (LBH 589) Administered in Combination With Ipilimumab in Subjects With Unresectable Stage III or Stage IV Melanoma
Actual Study Start Date :
Jan 7, 2014
Actual Primary Completion Date :
Sep 6, 2017
Anticipated Study Completion Date :
Apr 1, 2022

Arms and Interventions

ArmIntervention/Treatment
Experimental: Dose Escalation

Dose Escalation of Panobinostat + Ipilimumab. Participants will be assigned to receive a certain dose of panobinostat (5, 10, 15, or 20 mg) along with a dose of ipilimumab of 3 mg per kg (mg/kg) of body weight.

Drug: Panobinostat
Participants will be assigned to receive a certain dose of panobinostat (5, 10, 15, or 20 mg). The dose of panobinostat will depend on the time point the participant enters the study and the side effects of other participants already on the study.
Other Names:
  • LBH 589
  • Drug: Ipilimumab
    Dose of ipilimumab of 3 mg per kg (mg/kg) of body weight.
    Other Names:
  • BMS-734016
  • Outcome Measures

    Primary Outcome Measures

    1. Maximum Tolerated Dose (MTD) [Up to 36 months]

      MTD and recommended Phase 2 dose (RP2D) of panobinostat (PAN), administered in combination with ipilimumab (IPI) in participants with unresectable Stage III or Stage IV melanoma. The goal is to enroll up to 36 patients for determination of the MTD, but will be successfully concluded earlier if 12 patients are accrued at the dose determined to be the MTD, with 3 dose limiting toxicities (DLTs). All participants who receive study any drug therapy will be evaluated for safety. Safety assessments will be based on medical review of adverse event reports and the results of vital sign measurements, physical examinations, and clinical laboratory tests. Triplicate 12-lead electrocardiograms (ECGs) will be collected prior to dosing on Day 1 of induction cycle 1. MTD of PAN in milligrams (mg), with IPI at 3 mg/kg.

    Secondary Outcome Measures

    1. Immune Related Overall Response Rate (ORR) [Up to 36 months]

      Tumor response by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and immune-related Response Criteria (irRC). RECIST: Best overall response from start of treatment until disease progression/recurrence. Immune-related Complete Response (irCR): Complete disappearance of all tumor lesions for at least 4 weeks from date of documentation of irCR. Immune-related Partial Response (irPR): Sum of the products of the 2 largest perpendicular diameters of all index lesions, measured and captured as the Sum of Product of Diameters (SPD) baseline. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease (PD), taking as reference the smallest sum longest diameter (LD) since the treatment started. Immune-related Progressive Disease (irPD): At least a 25% increase in the SPD of all index lesions and new measurable lesions (irSPD) over the nadir SPD calculated for the index lesions.

    2. Progression Free Survival (PFS) [Up to 6 months]

      Progression Free Survival (PFS): is defined for each participant as the time from first dosing to the first observation of disease progression or death due to any cause. If a subject has not progressed or died at the time of analysis, PFS will be censored on the date of the last disease assessment. PFS will be calculated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Progressive Disease (PD) = 20% increase in the sum of the longest diameter of target lesions.

    3. Overall Survival (OS) [36 months]

      Overall survival: The time from randomization until death from any cause.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Men and women ≥ 18 years old

    • Participants must be ipilimumab naïve with progressive unresectable Stage III or Stage IV melanoma who are either treatment naïve or may have been treated with up to 3 prior treatments for melanoma (e.g., chemotherapy, biologic or targeted therapy or IL-2).

    • Histologic or cytologic confirmation of stage III or stage IV melanoma

    • Measurable disease at baseline as assessed by CT and/or MRI

    • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

    • Screening laboratory values must meet the following criteria: white blood count (WBCs) ≥ 2000/μL; Neutrophils ≥ 1500/μL; Platelets ≥ 100 x 10^3/μL; Hemoglobin ≥ 9.0 g/dL; Creatinine Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or creatinine clearance > 40 mL/minute (using Cockcroft/Gault formula); aspartic transaminase (AST) ≤ 3 x ULN; alanine transaminase (ALT) ≤ 3 x ULN; Total Bilirubin ≤ 1.5 x ULN (except those with Gilbert Syndrome who must have total bilirubin < 3.0 mg/dL)

    • Men and women of childbearing potential (WOCBP) must be using an acceptable method of contraception to avoid pregnancy throughout the study and for at least 12 weeks after the last dose of investigational product in such a manner that the risk of pregnancy is minimized. Women must have a negative serum pregnancy test within 72 hours prior to the start of investigational product.

    Exclusion Criteria:
    • Known or suspected brain metastasis, or brain as the only site of disease, with the following exceptions: controlled brain metastasis (no radiographic progression at least 4 weeks following radiation and/or surgical treatment, off steroids for at least 4 weeks, and have no new or progressing neurological signs or symptoms); history of prior malignancy with the exception of carcinoma in situ of the cervix or other malignancy diagnosed > 2 years ago that has undergone potentially curative therapy with no evidence of disease for the last ≥ 2 years and that is deemed by the investigator to be at a low risk of recurrence

    • Active autoimmune disease or a history of known or suspected autoimmune disease with the exception of subjects with isolated vitiligo, treated thyroiditis or resolved childhood asthma/atopy

    • Known human immunodeficiency virus (HIV), active hepatitis A, or hepatitis B or C infection

    • History of any hepatitis (e.g., alcohol or non-alcohol steatohepatitis (NASH), drug- related, autoimmune)

    • Evidence of active infection that requires anti-bacterial, anti-viral, or anti-fungal therapy ≤ 7 days prior to initiation of study drug therapy

    • History of acute diverticulitis, or current chronic diarrhea

    • Active peptic ulcer disease even if asymptomatic

    • History of adrenal insufficiency (including subjects using replacement therapy)

    • Prior organ allograft or allogeneic bone marrow transplantation

    • Uncontrolled or significant cardiovascular disease including, but not limited to, any of the following: Myocardial infarction within the past 6 months; Uncontrolled angina within the past 6 months; Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation or Torsades de pointes). Controlled atrial fibrillation by itself is not an exclusion criterion.; Baseline corrected QT interval (QTc) interval greater than 500 milliseconds

    • Baseline toxicities from prior anti-cancer treatments > Grade 1

    • Inability to be venipunctured and/or tolerate venous access

    • Any major surgery within 4 weeks or a diagnostic procedure (e.g. incision, needle biopsy) within 1 day of study drug administration

    • Any current or recent (within 3 months) gastrointestinal disease that could potentially impact the ability to swallow and/or absorb study drug (i.e., gastrointestinal surgery, malabsorption syndrome)

    • Diabetes mellitus uncontrolled by medication

    • Known drug or alcohol abuse

    • Presence of underlying medical condition that in the opinion of the Investigator or Sponsor could adversely affect the ability of the subject to comply with or tolerate study procedures and/or study therapy, or confound the ability to interpret the tolerability of combined administration of panobinostat and ipilimumab in treated subjects

    • History of allergy to components of ipilimumab or panobinostat, or known allergy to other antibody therapies.

    • WOCBP who are unwilling or unable to use an acceptable method to minimize the risk of pregnancy for the entire study period and for at least 12 weeks after the last dose of investigational product

    • Women who are pregnant or breastfeeding

    • Women with a positive pregnancy test on enrollment or prior to investigational product administration

    • Sexually active fertile men not using effective birth control if their partners are WOCBP

    • Exposure to any investigational drug within 4 weeks of study drug administration.

    • Any anti-cancer therapy (e.g., chemotherapy, biologics, radiotherapy, or hormonal treatment) within 4 weeks or at least 5 half-lives (whichever is longer) of study drug administration

    • Prior therapy with an anti-CTLA4 antibody or an HDAC inhibitor

    • Concurrent chemotherapy, hormonal therapy, immunotherapy regimens, or radiation therapy, standard or investigational

    • Prisoners or subjects who are involuntarily incarcerated

    • Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1H. Lee Moffitt Cancer Center and Research InstituteTampaFloridaUnited States33612

    Sponsors and Collaborators

    • H. Lee Moffitt Cancer Center and Research Institute
    • Novartis

    Investigators

    • Principal Investigator: Nikhil Khushalani, M.D., H. Lee Moffitt Cancer Center and Research Institute

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    H. Lee Moffitt Cancer Center and Research Institute
    ClinicalTrials.gov Identifier:
    NCT02032810
    Other Study ID Numbers:
    • MCC-17439
    First Posted:
    Jan 10, 2014
    Last Update Posted:
    Nov 16, 2021
    Last Verified:
    Nov 1, 2021
    Keywords provided by H. Lee Moffitt Cancer Center and Research Institute
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment DetailsParticipants were enrolled at Moffitt Cancer Center, November 2014 through November 2016.
    Pre-assignment Detail
    Arm/Group TitlePanobinostat 5 mgPanobinostat 10 mg
    Arm/Group DescriptionParticipants who received 5 mg of Panobinostat along with 3 mg IpilimumabParticipants who received Panobinostat 10 mg along with 3 mg Ipilimumab
    Period Title: Overall Study
    STARTED611
    COMPLETED611
    NOT COMPLETED00

    Baseline Characteristics

    Arm/Group TitlePanobinostat 5 mgPanobinostat 10 mgTotal
    Arm/Group DescriptionParticipants who received 5 mg of Panobinostat along with 3 mg IpililumabParticipants who received 10 mg of Panobinostat along with 3 mg IpililumabTotal of all reporting groups
    Overall Participants61117
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    64
    66
    66
    Sex: Female, Male (Count of Participants)
    Female
    2
    33.3%
    2
    18.2%
    4
    23.5%
    Male
    4
    66.7%
    9
    81.8%
    13
    76.5%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    1
    9.1%
    1
    5.9%
    Not Hispanic or Latino
    6
    100%
    10
    90.9%
    16
    94.1%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    White
    6
    100%
    11
    100%
    17
    100%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    6
    100%
    11
    100%
    17
    100%

    Outcome Measures

    1. Primary Outcome
    TitleMaximum Tolerated Dose (MTD)
    DescriptionMTD and recommended Phase 2 dose (RP2D) of panobinostat (PAN), administered in combination with ipilimumab (IPI) in participants with unresectable Stage III or Stage IV melanoma. The goal is to enroll up to 36 patients for determination of the MTD, but will be successfully concluded earlier if 12 patients are accrued at the dose determined to be the MTD, with 3 dose limiting toxicities (DLTs). All participants who receive study any drug therapy will be evaluated for safety. Safety assessments will be based on medical review of adverse event reports and the results of vital sign measurements, physical examinations, and clinical laboratory tests. Triplicate 12-lead electrocardiograms (ECGs) will be collected prior to dosing on Day 1 of induction cycle 1. MTD of PAN in milligrams (mg), with IPI at 3 mg/kg.
    Time FrameUp to 36 months

    Outcome Measure Data

    Analysis Population Description
    All participants
    Arm/Group TitleDose Escalation of Panobinostat, Plus Ipilimumab
    Arm/Group DescriptionEligible participants with unresectable stage 3/4 MEL, up to 3 prior lines of therapy, and adequate laboratory values were treated with oral PAN 5 mg thrice weekly (TIW) plus IPI at 3 mg/kg IV every 3 weeks X 4 doses, followed by maintenance PAN until progression or intolerance. Using a modified Ji design, PAN dose escalation by 5 mg was planned in 3-12 participant cohorts up to a maximum dose of 20 mg TIW, without intra-participant dose escalation. Dose limiting toxicity (DLT) was assessed up to day 84 from start of therapy.
    Measure Participants17
    Number [mg]
    5
    2. Secondary Outcome
    TitleImmune Related Overall Response Rate (ORR)
    DescriptionTumor response by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and immune-related Response Criteria (irRC). RECIST: Best overall response from start of treatment until disease progression/recurrence. Immune-related Complete Response (irCR): Complete disappearance of all tumor lesions for at least 4 weeks from date of documentation of irCR. Immune-related Partial Response (irPR): Sum of the products of the 2 largest perpendicular diameters of all index lesions, measured and captured as the Sum of Product of Diameters (SPD) baseline. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease (PD), taking as reference the smallest sum longest diameter (LD) since the treatment started. Immune-related Progressive Disease (irPD): At least a 25% increase in the SPD of all index lesions and new measurable lesions (irSPD) over the nadir SPD calculated for the index lesions.
    Time FrameUp to 36 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitlePanobinostat 5 mgPanobinostat 10 mg
    Arm/Group DescriptionParticipants who received 5 mg of Panobinostat along with 3 mg IpilimumabParticipants who received Panobinostat 10 mg along with 3 mg Ipilimumab
    Measure Participants611
    Partial Response
    1
    16.7%
    1
    9.1%
    Complete Response
    0
    0%
    0
    0%
    Stable Disease
    3
    50%
    3
    27.3%
    3. Secondary Outcome
    TitleProgression Free Survival (PFS)
    DescriptionProgression Free Survival (PFS): is defined for each participant as the time from first dosing to the first observation of disease progression or death due to any cause. If a subject has not progressed or died at the time of analysis, PFS will be censored on the date of the last disease assessment. PFS will be calculated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Progressive Disease (PD) = 20% increase in the sum of the longest diameter of target lesions.
    Time FrameUp to 6 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitlePanobinostat 5 mgPanobinostat 10 mg
    Arm/Group DescriptionParticipants who received 5 mg of Panobinostat along with 3 mg IpilimumabParticipants who received 10 mg of Panobinostat along with 3 mg of Ipilimumab
    Measure Participants611
    Median (95% Confidence Interval) [Months]
    4.19
    1.81
    4. Secondary Outcome
    TitleOverall Survival (OS)
    DescriptionOverall survival: The time from randomization until death from any cause.
    Time Frame36 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitlePanobinostat 5 mgPanobinostat 10 mg
    Arm/Group DescriptionParticipants who received 5 mg of Panobinostat along with 3 mg of IpilimumabParticipants who received 10 mg Panobinostat along with 3 mg Ipilimumab
    Measure Participants611
    Median (95% Confidence Interval) [Months]
    25.91
    12

    Adverse Events

    Time Frame3 years, 9 months
    Adverse Event Reporting Description
    Arm/Group TitlePanobinostat 5 mgPanobinostat 10 mg
    Arm/Group DescriptionParticipants who received 5 mg of Panobinostat along with 3 mg IpililumabParticipants who received 10 mg of Panobinostat along with 3 mg Ipililumab
    All Cause Mortality
    Panobinostat 5 mgPanobinostat 10 mg
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total1/6 (16.7%) 0/11 (0%)
    Serious Adverse Events
    Panobinostat 5 mgPanobinostat 10 mg
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total4/6 (66.7%) 7/11 (63.6%)
    Blood and lymphatic system disorders
    Anemia1/6 (16.7%) 10/11 (0%) 0
    Leukocytosis0/6 (0%) 01/11 (9.1%) 1
    Cardiac disorders
    Sinus tachycardia0/6 (0%) 01/11 (9.1%) 1
    Endocrine disorders
    Endocrine disorders - Other, Hypophysitis0/6 (0%) 01/11 (9.1%) 1
    Hypothyroidism1/6 (16.7%) 10/11 (0%) 0
    Gastrointestinal disorders
    Diarrhea0/6 (0%) 03/11 (27.3%) 3
    Nausea1/6 (16.7%) 13/11 (27.3%) 4
    Vomiting1/6 (16.7%) 12/11 (18.2%) 2
    General disorders
    Death NOS1/6 (16.7%) 10/11 (0%) 0
    Fatigue0/6 (0%) 03/11 (27.3%) 3
    Fever0/6 (0%) 02/11 (18.2%) 3
    Pain - Left groin/leg0/6 (0%) 01/11 (9.1%) 1
    Infections and infestations
    Infections and infestations - Other, Tested positive for adenovirus0/6 (0%) 01/11 (9.1%) 1
    Lung infection - Pneumonia0/6 (0%) 01/11 (9.1%) 1
    Sepsis0/6 (0%) 01/11 (9.1%) 1
    Investigations
    Investigations - Other, Hypophysitis2/6 (33.3%) 20/11 (0%) 0
    Platelet count decreased0/6 (0%) 01/11 (9.1%) 1
    Serum amylase increased0/6 (0%) 01/11 (9.1%) 1
    Metabolism and nutrition disorders
    Anorexia0/6 (0%) 01/11 (9.1%) 1
    Dehydration1/6 (16.7%) 11/11 (9.1%) 1
    Hypocalcemia0/6 (0%) 01/11 (9.1%) 1
    Hypokalemia0/6 (0%) 01/11 (9.1%) 1
    Hyponatremia1/6 (16.7%) 11/11 (9.1%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms - Other, basal cell carcinoma0/6 (0%) 01/11 (9.1%) 1
    Nervous system disorders
    Dizziness0/6 (0%) 01/11 (9.1%) 1
    Psychiatric disorders
    Confusion0/6 (0%) 02/11 (18.2%) 2
    Renal and urinary disorders
    Acute kidney injury0/6 (0%) 03/11 (27.3%) 3
    Renal and urinary disorders - Other, Hydronephrosis1/6 (16.7%) 10/11 (0%) 0
    Urinary retention0/6 (0%) 01/11 (9.1%) 1
    Respiratory, thoracic and mediastinal disorders
    Cough0/6 (0%) 01/11 (9.1%) 1
    Dyspnea0/6 (0%) 01/11 (9.1%) 1
    Skin and subcutaneous tissue disorders
    Rash maculopapular0/6 (0%) 02/11 (18.2%) 2
    Vascular disorders
    Hypotension0/6 (0%) 02/11 (18.2%) 2
    Other (Not Including Serious) Adverse Events
    Panobinostat 5 mgPanobinostat 10 mg
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total6/6 (100%) 11/11 (100%)
    Blood and lymphatic system disorders
    Anemia1/6 (16.7%) 11/11 (9.1%) 1
    Cardiac disorders
    Cardiac disorders - Other0/6 (0%) 01/11 (9.1%) 1
    Palpitations0/6 (0%) 01/11 (9.1%) 3
    Sinus bradycardia1/6 (16.7%) 10/11 (0%) 0
    Ear and labyrinth disorders
    Ear pain0/6 (0%) 01/11 (9.1%) 1
    Vertigo1/6 (16.7%) 10/11 (0%) 0
    Endocrine disorders
    Hypothyroidism2/6 (33.3%) 24/11 (36.4%) 5
    Endocrine disorders - Other2/6 (33.3%) 33/11 (27.3%) 6
    Adrenal insufficiency1/6 (16.7%) 10/11 (0%) 0
    Eye disorders
    Conjunctivitis0/6 (0%) 01/11 (9.1%) 1
    Dry eye0/6 (0%) 01/11 (9.1%) 1
    Eye disorders - Other0/6 (0%) 01/11 (9.1%) 1
    Gastrointestinal disorders
    Diarrhea5/6 (83.3%) 69/11 (81.8%) 33
    Nausea5/6 (83.3%) 88/11 (72.7%) 14
    Vomiting4/6 (66.7%) 65/11 (45.5%) 12
    Abdominal pain4/6 (66.7%) 43/11 (27.3%) 6
    Constipation2/6 (33.3%) 24/11 (36.4%) 4
    Dry mouth1/6 (16.7%) 13/11 (27.3%) 4
    Bloating1/6 (16.7%) 11/11 (9.1%) 1
    Colitis1/6 (16.7%) 11/11 (9.1%) 1
    Gastrointestinal disorders - Other1/6 (16.7%) 11/11 (9.1%) 2
    Mucositis oral0/6 (0%) 01/11 (9.1%) 1
    General disorders
    Fatigue5/6 (83.3%) 1110/11 (90.9%) 20
    Pain1/6 (16.7%) 13/11 (27.3%) 4
    Fever1/6 (16.7%) 12/11 (18.2%) 4
    General disorders and administration site conditions - Other2/6 (33.3%) 20/11 (0%) 0
    Malaise1/6 (16.7%) 11/11 (9.1%) 2
    Chills0/6 (0%) 01/11 (9.1%) 1
    Edema limbs0/6 (0%) 01/11 (9.1%) 1
    Flu like symptoms0/6 (0%) 01/11 (9.1%) 1
    Infusion related reaction1/6 (16.7%) 10/11 (0%) 0
    Localized edema0/6 (0%) 01/11 (9.1%) 1
    Non-cardiac chest pain0/6 (0%) 01/11 (9.1%) 1
    Immune system disorders
    Immune system disorders - Other0/6 (0%) 01/11 (9.1%) 1
    Infections and infestations
    Lung infection0/6 (0%) 01/11 (9.1%) 2
    Upper respiratory infection0/6 (0%) 01/11 (9.1%) 2
    Urinary tract infection0/6 (0%) 01/11 (9.1%) 1
    Injury, poisoning and procedural complications
    Fracture0/6 (0%) 01/11 (9.1%) 1
    Postoperative hemorrhage0/6 (0%) 01/11 (9.1%) 1
    Investigations
    Platelet count decreased0/6 (0%) 03/11 (27.3%) 8
    Lipase increased1/6 (16.7%) 42/11 (18.2%) 4
    Serum amylase increased1/6 (16.7%) 12/11 (18.2%) 2
    Weight loss0/6 (0%) 03/11 (27.3%) 3
    Creatinine increased2/6 (33.3%) 20/11 (0%) 0
    Investigations - Other2/6 (33.3%) 30/11 (0%) 0
    Alanine aminotransferase increased0/6 (0%) 01/11 (9.1%) 1
    Aspartate aminotransferase increased0/6 (0%) 01/11 (9.1%) 1
    Electrocardiogram QT corrected interval prolonged0/6 (0%) 01/11 (9.1%) 1
    Metabolism and nutrition disorders
    Anorexia3/6 (50%) 49/11 (81.8%) 10
    Dehydration2/6 (33.3%) 23/11 (27.3%) 3
    Hyponatremia1/6 (16.7%) 43/11 (27.3%) 9
    Hypokalemia0/6 (0%) 01/11 (9.1%) 1
    Hyperglycemia0/6 (0%) 01/11 (9.1%) 2
    Hypoalbuminemia0/6 (0%) 01/11 (9.1%) 1
    Musculoskeletal and connective tissue disorders
    Myalgia0/6 (0%) 04/11 (36.4%) 4
    Back pain1/6 (16.7%) 12/11 (18.2%) 3
    Arthralgia0/6 (0%) 02/11 (18.2%) 2
    Arthritis0/6 (0%) 01/11 (9.1%) 1
    Generalized muscle weakness1/6 (16.7%) 10/11 (0%) 0
    Pain in extremity0/6 (0%) 01/11 (9.1%) 1
    Nervous system disorders
    Dizziness1/6 (16.7%) 52/11 (18.2%) 4
    Dysgeusia0/6 (0%) 02/11 (18.2%) 2
    Headache1/6 (16.7%) 21/11 (9.1%) 3
    Amnesia1/6 (16.7%) 10/11 (0%) 0
    Concentration impairment1/6 (16.7%) 10/11 (0%) 0
    Nervous system disorders - Other0/6 (0%) 01/11 (9.1%) 2
    Syncope1/6 (16.7%) 10/11 (0%) 0
    Psychiatric disorders
    Confusion1/6 (16.7%) 11/11 (9.1%) 1
    Insomnia1/6 (16.7%) 12/11 (18.2%) 2
    Anxiety1/6 (16.7%) 10/11 (0%) 0
    Depression0/6 (0%) 01/11 (9.1%) 1
    Renal and urinary disorders
    Hematuria0/6 (0%) 03/11 (27.3%) 3
    Urinary frequency1/6 (16.7%) 12/11 (18.2%) 2
    Acute kidney injury0/6 (0%) 01/11 (9.1%) 1
    Urinary retention0/6 (0%) 01/11 (9.1%) 1
    Respiratory, thoracic and mediastinal disorders
    Dyspnea2/6 (33.3%) 25/11 (45.5%) 6
    Cough2/6 (33.3%) 22/11 (18.2%) 2
    Productive cough2/6 (33.3%) 20/11 (0%) 0
    Hoarseness0/6 (0%) 01/11 (9.1%) 1
    Pneumonitis0/6 (0%) 01/11 (9.1%) 1
    Respiratory, thoracic and mediastinal disorders - Other0/6 (0%) 01/11 (9.1%) 1
    Sore throat0/6 (0%) 01/11 (9.1%) 1
    Skin and subcutaneous tissue disorders
    Rash maculopapular1/6 (16.7%) 14/11 (36.4%) 5
    Pruritus1/6 (16.7%) 13/11 (27.3%) 3
    Dry skin0/6 (0%) 01/11 (9.1%) 1
    Skin and subcutaneous tissue disorders - Other0/6 (0%) 01/11 (9.1%) 3
    Skin ulceration0/6 (0%) 01/11 (9.1%) 1
    Vascular disorders
    Hypotension0/6 (0%) 02/11 (18.2%) 4
    Hot flashes1/6 (16.7%) 10/11 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/TitleDr. Nikhil I. Khushalani
    OrganizationH. Lee Moffitt Cancer Center and Research Institute
    Phone813-745-3437
    Emailnikhil.khushalani@moffitt.org
    Responsible Party:
    H. Lee Moffitt Cancer Center and Research Institute
    ClinicalTrials.gov Identifier:
    NCT02032810
    Other Study ID Numbers:
    • MCC-17439
    First Posted:
    Jan 10, 2014
    Last Update Posted:
    Nov 16, 2021
    Last Verified:
    Nov 1, 2021