Enzalutamide in Combination With Gemcitabine and Cisplatin in Bladder Cancer

Sponsor
H. Lee Moffitt Cancer Center and Research Institute (Other)
Overall Status
Completed
CT.gov ID
NCT02300610
Collaborator
(none)
10
Enrollment
2
Locations
2
Arms
50.2
Actual Duration (Months)
5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The main purpose of this study is to find out the dose of enzalutamide that can be safely given with gemcitabine and cisplatin in patients with advanced bladder cancer. Researchers also want to find out the side effects of these drugs when given together. This study will also help in finding out the effect on tumor of the combination of enzalutamide, gemcitabine and cisplatin.

Detailed Description

For the phase 1 dose escalation phase, the starting dose of enzalutamide will be 80 mg orally once a day (Level 1). The dosing regimen of cisplatin and gemcitabine will be at standard doses of Gemcitabine at 1000 mg/m^2 IV on days 1, 8 and cisplatin at 70 mg/m2 IV on day 1, repeated every 21 days for total of 6 cycles.

Three patients will be treated dose level 1 (enzalutamide 80 mg daily). If 0 patients experience dose limiting toxicity (DLT), dose escalation will be done to level 2 of enzalutamide 160 mg daily. If 1 patient experiences DLT, 3 more patients will be treated at the same dose level; if 1 of 6 experiences DLT, escalate the dose to next level, and if 2 or more of 6 experiences DLT, the dose level 1 (80 mg enzalutamide) will be the recommended dose for dose expansion cohort.

The cohort expansion will then be done by enrolling 12 patients with stage IV bladder cancer, who express androgen receptor (AR) staining of 1+ and above by immunohistochemistry (IHC), to determine the safety and tolerability of cisplatin and gemcitabine with the recommended dose level of enzalutamide (80 mg or 160 mg, depending upon the safety results from dose escalation part) in this expanded cohort of patients with AR + bladder cancer.

Enzalutamide would be continued after completion of 6 cycles of gemcitabine-cisplatin for patients exhibiting a response or stable disease, until they experience disease progression.

Study Design

Study Type:
Interventional
Actual Enrollment :
10 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I/1b Study of Enzalutamide in Combination With Gemcitabine and Cisplatin in Bladder Cancer
Actual Study Start Date :
Feb 11, 2015
Actual Primary Completion Date :
Aug 7, 2017
Actual Study Completion Date :
Apr 19, 2019

Arms and Interventions

ArmIntervention/Treatment
Experimental: Dose Escalation

Dose Escalation: Begin with Level 1 dose of enzalutamide (orally), with standard doses of cisplatin and gemcitabine via intravenous (IV).

Drug: Enzalutamide
Enzalutamide orally once a day. Dose Escalation Level 1: 80 mg; Level 2: 160 mg. Dose Expansion at recommended dose level, after dose escalation.
Other Names:
  • MDV3100
  • XTANDI®
  • Drug: Cisplatin
    Cisplatin at 70 mg/m^2 IV on day 1, repeated every 21 days for total of 6 cycles.
    Other Names:
  • Platinol®
  • Platinol®-AQ
  • Drug: Gemcitabine
    Gemcitabine at 1000 mg/m^2 IV on days 1, 8, repeated every 21 days for total of 6 cycles.
    Other Names:
  • Gemzar ®
  • Experimental: Dose Expansion

    Dose Expansion: Enzalutamide at recommended dose level with standard doses of cisplatin and gemcitabine.

    Drug: Enzalutamide
    Enzalutamide orally once a day. Dose Escalation Level 1: 80 mg; Level 2: 160 mg. Dose Expansion at recommended dose level, after dose escalation.
    Other Names:
  • MDV3100
  • XTANDI®
  • Drug: Cisplatin
    Cisplatin at 70 mg/m^2 IV on day 1, repeated every 21 days for total of 6 cycles.
    Other Names:
  • Platinol®
  • Platinol®-AQ
  • Drug: Gemcitabine
    Gemcitabine at 1000 mg/m^2 IV on days 1, 8, repeated every 21 days for total of 6 cycles.
    Other Names:
  • Gemzar ®
  • Outcome Measures

    Primary Outcome Measures

    1. Recommended Dose of Enzalutamide [Up to 6 months]

      Dose Escalation. Maximum Tolerated Dose (MTD) of Enzalutamide when given with Cisplatin and Gemcitabine at standard doses. Dose Level 1: 80 mg Enzalutamide; Dose Level 2: 160 mg Enzalutamide. Dose-Limiting Toxicity (DLT) is defined as any of the following occurring in the first 21 days (cycle 1) of study participation that are considered at least possibly related to enzalutamide administration. Toxicities that are in the opinion of the investigator(s) attributable exclusively to gemcitabine or cisplatin will not be considered DLT. 7 consecutive missed doses (out of 21 doses) of enzalutamide in 21 days due to study drug related toxicity. Missed day 8 dose of gemcitabine in cycle 1 will not be considered DLT. Delay of greater than 3 weeks from scheduled date in initiating cycle 2 due to study drug related toxicity. Discontinuation of a patient due to study drug related toxicity before completing cycle 1.

    Secondary Outcome Measures

    1. Overall Response Rate (ORR): Complete Response (CR) + Partial Response (PR) [Up to 6 months]

      Dose Expansion. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

    2. Progression Free Survival (PFS) [14 months]

      Dose Expansion. PFS is defined as the time from randomization until objective tumor progression or death. Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).

    3. Overall Survival (OS) [Up to 24 Months]

      Dose Expansion. Overall survival is defined as the time from randomization until death from any cause, and is measured in the intent-to-treat population.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Cytologically or histologically confirmed evidence of transitional cell carcinoma of bladder, renal pelvis, ureter or urethra.

    • Patients with Stage IV (locally advanced or metastatic) disease. Must have measurable disease, as per Response Evaluation Criteria in Solid Tumors (RECIST).

    • Minimum of 4 weeks since any major surgery, completion of radiation.

    • Prior treatment with cytotoxic chemotherapy is not a requirement, but allowed only if used in neoadjuvant, adjuvant or for bladder preserving protocols, as long as was administered > 6 months prior to starting study.

    • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.

    • Life expectancy 12 weeks or more.

    • Must have normal organ and marrow function.

    • Women of childbearing potential must have a negative serum or urine pregnancy test within 14 days of the administration of the first study treatment. Women must not be lactating.

    • Sexually active women of childbearing age and men should be willing to follow birth control guidelines.

    • Should be able to swallow enzalutamide and comply with study requirements.

    Exclusion Criteria:
    • Prior treatment with any cytotoxic chemotherapy in metastatic setting. Prior treatment with cytotoxic chemotherapy is allowed only if used in neoadjuvant, adjuvant or for bladder preserving protocols, as long as was administered > 6 months prior to starting study.

    • Have undergone major surgery within 4 weeks prior to study enrollment.

    • Chronic treatment with steroids or any other immunosuppressant drugs.

    • Should not receive immunization with attenuated live vaccines during study period or within 1 week of study entry.

    • History of seizures, predisposing factors for seizures, including underlying brain injury with loss of consciousness within previous 12 months, transient ischemic attack within previous 12 months, cerebral vascular accident or brain arteriovenous malformation.

    • Untreated brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases.

    • Congestive heart failure (NYHA Class III or IV), unstable angina, sustained ventricular tachycardia, ventricular fibrillation, clinically significant bradycardia, advanced heart block or a history of acute myocardial infarction within the 6 months preceding enrollment.

    • Known history of HIV.

    • Have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study.

    • Women who are pregnant or breast feeding, or women/men able to conceive and unwilling to practice birth control guidelines.

    • Concurrent medications which strongly inhibit or induce CYP enzymes (gemfibrozil, Rifampin, carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, bosentan, efavirenz, etravirine, modafinil, nafcillin, St. John's Wort).

    • History of stage III or greater cancer, except basal or squamous cell skin cancers adequately treated or any other stage I or II cancer adequately treated and disease-free for ≥ 2 years. Incidental findings of stage I or II prostate cancer that is considered to be cured with radical cystoprostatectomy is allowed.

    • Prior use of enzalutamide.

    • Radiation therapy via external beam or brachytherapy within 28 days of registration.

    • Patients who are ineligible to receive cisplatin: Creatinine clearance of less than 60 mL/minute, hearing loss of 25 decibel (dB) at 2 contiguous frequencies, grade 2 or higher peripheral neuropathy, or New York Heart Association Class III or higher heart failure.

    • Allergy/sensitivity to any study drug (gemcitabine, cisplatin, enzalutamide), or drugs chemically related to study drug, or excipients.

    • Brain metastases (including treated or stable brain metastases)

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1H. Lee Moffitt Cancer Center and Research InstituteTampaFloridaUnited States33612
    2University of Minnesota, Masonic Cancer CenterMinneapolisMinnesotaUnited States55455

    Sponsors and Collaborators

    • H. Lee Moffitt Cancer Center and Research Institute

    Investigators

    • Principal Investigator: Jingsong Zhang, M.D., Ph.D., H. Lee Moffitt Cancer Center and Research Institute
    • Study Chair: Shilpa Gupta, M.D., University of Minnesota Masonic Cancer Center

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    H. Lee Moffitt Cancer Center and Research Institute
    ClinicalTrials.gov Identifier:
    NCT02300610
    Other Study ID Numbers:
    • MCC-17924
    First Posted:
    Nov 25, 2014
    Last Update Posted:
    Aug 1, 2019
    Last Verified:
    Jun 1, 2019
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by H. Lee Moffitt Cancer Center and Research Institute
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment DetailsParticipants were recruited at Moffitt Cancer Center and the University of Minnesota Masonic Cancer Center, February 2015 through August 2017.
    Pre-assignment Detail
    Arm/Group TitleDose Escalation: Level 1 DoseDose Escalation- Level 2 DoseDose Expansion
    Arm/Group DescriptionDose Escalation: Level 1 dose of 80 mg enzalutamide (orally), with standard doses of cisplatin and gemcitabine via intravenous (IV).Dose Escalation: Level 2 dose of 160 mg enzalutamide (orally), with standard doses of cisplatin and gemcitabine via intravenous (IV).Enzalutamide at MTD (160 mg) with standard doses of cisplatin and gemcitabine.
    Period Title: Overall Study
    STARTED334
    COMPLETED233
    NOT COMPLETED101

    Baseline Characteristics

    Arm/Group TitleDose Escalation: Level 1 DoseDose Escalation: Level 2 DoseDose ExpansionTotal
    Arm/Group DescriptionDose Escalation: Level 1 dose of 80 mg enzalutamide (orally), with standard doses of cisplatin and gemcitabine via intravenous (IV).Dose Escalation: Level 2 dose of 160 mg enzalutamide (orally), with standard doses of cisplatin and gemcitabine via intravenous (IV).Dose Expansion: Enzalutamide at recommended dose level with standard doses of cisplatin and gemcitabine.Total of all reporting groups
    Overall Participants33410
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    2
    66.7%
    1
    33.3%
    2
    50%
    5
    50%
    >=65 years
    1
    33.3%
    2
    66.7%
    2
    50%
    5
    50%
    Age (years) [Mean (Full Range) ]
    Mean (Full Range) [years]
    65
    66.6
    65
    65.5
    Sex: Female, Male (Count of Participants)
    Female
    0
    0%
    0
    0%
    1
    25%
    1
    10%
    Male
    3
    100%
    3
    100%
    3
    75%
    9
    90%
    Race/Ethnicity, Customized (Count of Participants)
    White Non-Hispanic
    3
    100%
    3
    100%
    4
    100%
    10
    100%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Hispanic or Latino
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Other
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    3
    100%
    3
    100%
    4
    100%
    10
    100%

    Outcome Measures

    1. Primary Outcome
    TitleRecommended Dose of Enzalutamide
    DescriptionDose Escalation. Maximum Tolerated Dose (MTD) of Enzalutamide when given with Cisplatin and Gemcitabine at standard doses. Dose Level 1: 80 mg Enzalutamide; Dose Level 2: 160 mg Enzalutamide. Dose-Limiting Toxicity (DLT) is defined as any of the following occurring in the first 21 days (cycle 1) of study participation that are considered at least possibly related to enzalutamide administration. Toxicities that are in the opinion of the investigator(s) attributable exclusively to gemcitabine or cisplatin will not be considered DLT. 7 consecutive missed doses (out of 21 doses) of enzalutamide in 21 days due to study drug related toxicity. Missed day 8 dose of gemcitabine in cycle 1 will not be considered DLT. Delay of greater than 3 weeks from scheduled date in initiating cycle 2 due to study drug related toxicity. Discontinuation of a patient due to study drug related toxicity before completing cycle 1.
    Time FrameUp to 6 months

    Outcome Measure Data

    Analysis Population Description
    All participants in Dose Escalation arm.
    Arm/Group TitleDose Escalation
    Arm/Group DescriptionDose Escalation: Begin with Level 1 dose of enzalutamide (orally), with standard doses of cisplatin and gemcitabine via intravenous (IV).
    Measure Participants6
    Number [mg]
    160
    2. Secondary Outcome
    TitleOverall Response Rate (ORR): Complete Response (CR) + Partial Response (PR)
    DescriptionDose Expansion. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
    Time FrameUp to 6 months

    Outcome Measure Data

    Analysis Population Description
    All participants evaluable at time of analysis.
    Arm/Group TitleDose Escalation: Level 1 DoseDose Escalation: Level 2 DoseDose Expansion
    Arm/Group DescriptionDose Escalation: Level 1 dose of 80 mg enzalutamide (orally), with standard doses of cisplatin and gemcitabine via intravenous (IV).Dose Escalation - Level 2 dose of 160 mg enzalutamide (orally) with standard dose of cisplatin and gemcitabine via intravenous (IV).Dose Expansion: Enzalutamide at MTD (160 mg) with standard doses of cisplatin and gemcitabine.
    Measure Participants334
    Partial Response
    0
    0%
    3
    100%
    1
    25%
    Progressive Disease
    1
    33.3%
    0
    0%
    0
    0%
    Stable Disease
    1
    33.3%
    0
    0%
    1
    25%
    Complete Response
    0
    0%
    0
    0%
    1
    25%
    Not Evaluable
    1
    33.3%
    0
    0%
    1
    25%
    3. Secondary Outcome
    TitleProgression Free Survival (PFS)
    DescriptionDose Expansion. PFS is defined as the time from randomization until objective tumor progression or death. Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).
    Time Frame14 months

    Outcome Measure Data

    Analysis Population Description
    All Participants.
    Arm/Group TitleDose Escalation: Level 1 DoseDose Escalation: Level 2 DoseDose Expansion
    Arm/Group DescriptionDose Escalation: Level 1 dose of 80 mg enzalutamide (orally), with standard doses of cisplatin and gemcitabine via intravenous (IV).Dose Escalation - Level 2 dose of 160 mg enzalutamide (orally) with standard dose of cisplatin and gemcitabine via intravenous (IV).Dose Expansion: Enzalutamide at MTD (160 mg) with standard doses of cisplatin and gemcitabine.
    Measure Participants334
    Median (95% Confidence Interval) [months]
    3.81
    14.63
    7.68
    4. Secondary Outcome
    TitleOverall Survival (OS)
    DescriptionDose Expansion. Overall survival is defined as the time from randomization until death from any cause, and is measured in the intent-to-treat population.
    Time FrameUp to 24 Months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleDose Escalation: Level 1 DoseDose Escalation: Level 2 DoseDose Expansion
    Arm/Group DescriptionDose Escalation: Level 1 dose of 80 mg enzalutamide (orally), with standard doses of cisplatin and gemcitabine via intravenous (IV).Dose Escalation: Level 2 dose of 160 mg enzalutamide (orally) with standard dose of cisplatin and gemcitabine via intravenous (IV).Dose Expansion: Enzalutamide at MTD (160 mg) with standard doses of cisplatin and gemcitabine.
    Measure Participants334
    Median (95% Confidence Interval) [months]
    4.14
    14.63
    10.03

    Adverse Events

    Time Frame2 years, 7 months
    Adverse Event Reporting Description Patient deaths listed in "all cause mortality" occurred after the Adverse Event reporting period, but within the Overall Survival follow-up period.
    Arm/Group TitleDose Escalation: Dose Level 1Dose Escalation: Level 2 DoseDose Expansion
    Arm/Group DescriptionDose Escalation: Level 1 dose of 80 mg enzalutamide (orally), with standard doses of cisplatin and gemcitabine via intravenous (IV).Dose Escalation: Level 2 dose of 160 mg enzalutamide (orally), with standard doses of cisplatin and gemcitabine via intravenous (IV).Dose Expansion: Enzalutamide at MTD (160 mg) with standard doses of cisplatin and gemcitabine.
    All Cause Mortality
    Dose Escalation: Dose Level 1Dose Escalation: Level 2 DoseDose Expansion
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total3/3 (100%) 3/3 (100%) 2/4 (50%)
    Serious Adverse Events
    Dose Escalation: Dose Level 1Dose Escalation: Level 2 DoseDose Expansion
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total2/3 (66.7%) 3/3 (100%) 3/4 (75%)
    Gastrointestinal disorders
    Nausea0/3 (0%) 01/3 (33.3%) 10/4 (0%) 0
    Oral pain0/3 (0%) 01/3 (33.3%) 10/4 (0%) 0
    Pancreatitis0/3 (0%) 00/3 (0%) 01/4 (25%) 2
    Small intestinal obstruction0/3 (0%) 01/3 (33.3%) 10/4 (0%) 0
    Vomiting0/3 (0%) 01/3 (33.3%) 10/4 (0%) 0
    Infections and infestations
    Device related infection1/3 (33.3%) 10/3 (0%) 00/4 (0%) 0
    Kidney infection0/3 (0%) 01/3 (33.3%) 10/4 (0%) 0
    Lung infection1/3 (33.3%) 10/3 (0%) 00/4 (0%) 0
    Sepsis1/3 (33.3%) 10/3 (0%) 01/4 (25%) 1
    Urinary tract infection0/3 (0%) 00/3 (0%) 01/4 (25%) 1
    Injury, poisoning and procedural complications
    Fall1/3 (33.3%) 10/3 (0%) 00/4 (0%) 0
    Investigations
    Creatinine increased0/3 (0%) 01/3 (33.3%) 10/4 (0%) 0
    Metabolism and nutrition disorders
    Dehydration0/3 (0%) 00/3 (0%) 01/4 (25%) 1
    Hypokalemia0/3 (0%) 00/3 (0%) 01/4 (25%) 1
    Hyponatremia0/3 (0%) 01/3 (33.3%) 11/4 (25%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms benign, malignant and unspecified - Other0/3 (0%) 01/3 (33.3%) 10/4 (0%) 0
    Nervous system disorders
    Dysarthria0/3 (0%) 01/3 (33.3%) 10/4 (0%) 0
    Syncope1/3 (33.3%) 10/3 (0%) 00/4 (0%) 0
    Transient ischemic attacks0/3 (0%) 00/3 (0%) 01/4 (25%) 1
    Psychiatric disorders
    Agitation0/3 (0%) 01/3 (33.3%) 10/4 (0%) 0
    Confusion0/3 (0%) 01/3 (33.3%) 10/4 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Pneumothorax0/3 (0%) 01/3 (33.3%) 10/4 (0%) 0
    Vascular disorders
    Thromboembolic event1/3 (33.3%) 10/3 (0%) 00/4 (0%) 0
    Other (Not Including Serious) Adverse Events
    Dose Escalation: Dose Level 1Dose Escalation: Level 2 DoseDose Expansion
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total3/3 (100%) 3/3 (100%) 4/4 (100%)
    Blood and lymphatic system disorders
    Anemia2/3 (66.7%) 43/3 (100%) 194/4 (100%) 9
    Leukocytosis0/3 (0%) 01/3 (33.3%) 21/4 (25%) 1
    Cardiac disorders
    Sinus tachycardia0/3 (0%) 01/3 (33.3%) 11/4 (25%) 1
    Sinus bradycardia0/3 (0%) 01/3 (33.3%) 20/4 (0%) 0
    Ear and labyrinth disorders
    Tinnitus0/3 (0%) 01/3 (33.3%) 12/4 (50%) 2
    Hearing impaired0/3 (0%) 01/3 (33.3%) 10/4 (0%) 0
    Eye disorders
    Blurred vision0/3 (0%) 01/3 (33.3%) 11/4 (25%) 1
    Eye disorders - Other, specify0/3 (0%) 00/3 (0%) 01/4 (25%) 2
    Gastrointestinal disorders
    Nausea3/3 (100%) 33/3 (100%) 63/4 (75%) 4
    Vomiting1/3 (33.3%) 13/3 (100%) 32/4 (50%) 2
    Constipation1/3 (33.3%) 13/3 (100%) 31/4 (25%) 1
    Diarrhea1/3 (33.3%) 22/3 (66.7%) 32/4 (50%) 2
    Abdominal pain1/3 (33.3%) 11/3 (33.3%) 11/4 (25%) 1
    Bloating0/3 (0%) 02/3 (66.7%) 30/4 (0%) 0
    Dry mouth0/3 (0%) 02/3 (66.7%) 20/4 (0%) 0
    Gastrointestinal disorders - Other, specify1/3 (33.3%) 11/3 (33.3%) 10/4 (0%) 0
    Mucositis oral1/3 (33.3%) 11/3 (33.3%) 20/4 (0%) 0
    Duodenal ulcer0/3 (0%) 00/3 (0%) 01/4 (25%) 1
    Flatulence1/3 (33.3%) 10/3 (0%) 00/4 (0%) 0
    Gastrointestinal pain0/3 (0%) 01/3 (33.3%) 10/4 (0%) 0
    Oral pain0/3 (0%) 01/3 (33.3%) 20/4 (0%) 0
    Pancreatitis0/3 (0%) 00/3 (0%) 01/4 (25%) 1
    Rectal pain1/3 (33.3%) 10/3 (0%) 00/4 (0%) 0
    Small intestinal obstruction0/3 (0%) 01/3 (33.3%) 10/4 (0%) 0
    General disorders
    Fatigue3/3 (100%) 43/3 (100%) 53/4 (75%) 8
    Edema limbs1/3 (33.3%) 20/3 (0%) 01/4 (25%) 1
    Fever2/3 (66.7%) 20/3 (0%) 00/4 (0%) 0
    Non-cardiac chest pain1/3 (33.3%) 11/3 (33.3%) 10/4 (0%) 0
    Chills1/3 (33.3%) 10/3 (0%) 00/4 (0%) 0
    Infusion site extravasation1/3 (33.3%) 10/3 (0%) 00/4 (0%) 0
    Infections and infestations
    Urinary tract infection1/3 (33.3%) 11/3 (33.3%) 11/4 (25%) 1
    Bladder infection0/3 (0%) 00/3 (0%) 01/4 (25%) 1
    Catheter related infection0/3 (0%) 01/3 (33.3%) 10/4 (0%) 0
    Rhinitis infective0/3 (0%) 00/3 (0%) 01/4 (25%) 1
    Wound infection0/3 (0%) 01/3 (33.3%) 10/4 (0%) 0
    Injury, poisoning and procedural complications
    Fall1/3 (33.3%) 22/3 (66.7%) 22/4 (50%) 4
    Wound complication0/3 (0%) 01/3 (33.3%) 10/4 (0%) 0
    Investigations
    Platelet count decreased3/3 (100%) 33/3 (100%) 233/4 (75%) 13
    Lymphocyte count decreased0/3 (0%) 03/3 (100%) 122/4 (50%) 5
    Neutrophil count decreased0/3 (0%) 03/3 (100%) 122/4 (50%) 5
    Alkaline phosphatase increased0/3 (0%) 02/3 (66.7%) 52/4 (50%) 4
    Creatinine increased1/3 (33.3%) 32/3 (66.7%) 91/4 (25%) 2
    Weight loss2/3 (66.7%) 31/3 (33.3%) 31/4 (25%) 1
    White blood cell decreased0/3 (0%) 03/3 (100%) 61/4 (25%) 7
    Alanine aminotransferase increased1/3 (33.3%) 10/3 (0%) 01/4 (25%) 2
    Aspartate aminotransferase increased0/3 (0%) 01/3 (33.3%) 31/4 (25%) 1
    Activated partial thromboplastin time prolonged0/3 (0%) 00/3 (0%) 01/4 (25%) 1
    Blood bilirubin increased0/3 (0%) 00/3 (0%) 01/4 (25%) 1
    Electrocardiogram QT corrected interval prolonged0/3 (0%) 00/3 (0%) 01/4 (25%) 1
    Lipase increased0/3 (0%) 00/3 (0%) 01/4 (25%) 2
    Metabolism and nutrition disorders
    Hypoalbuminemia2/3 (66.7%) 22/3 (66.7%) 73/4 (75%) 4
    Hyponatremia3/3 (100%) 72/3 (66.7%) 42/4 (50%) 2
    Anorexia1/3 (33.3%) 12/3 (66.7%) 52/4 (50%) 2
    Hypomagnesemia1/3 (33.3%) 12/3 (66.7%) 42/4 (50%) 3
    Hyperkalemia2/3 (66.7%) 21/3 (33.3%) 81/4 (25%) 3
    Hypokalemia0/3 (0%) 01/3 (33.3%) 12/4 (50%) 13
    Dehydration0/3 (0%) 01/3 (33.3%) 31/4 (25%) 1
    Hypercalcemia0/3 (0%) 02/3 (66.7%) 50/4 (0%) 0
    Hypertriglyceridemia0/3 (0%) 02/3 (66.7%) 30/4 (0%) 0
    Hyperglycemia0/3 (0%) 01/3 (33.3%) 60/4 (0%) 0
    Hypermagnesemia0/3 (0%) 01/3 (33.3%) 10/4 (0%) 0
    Hypernatremia0/3 (0%) 01/3 (33.3%) 10/4 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia0/3 (0%) 01/3 (33.3%) 11/4 (25%) 1
    Back pain0/3 (0%) 01/3 (33.3%) 11/4 (25%) 2
    Pain in extremity1/3 (33.3%) 10/3 (0%) 01/4 (25%) 1
    Arthritis0/3 (0%) 01/3 (33.3%) 10/4 (0%) 0
    Bone pain0/3 (0%) 01/3 (33.3%) 10/4 (0%) 0
    Generalized muscle weakness0/3 (0%) 00/3 (0%) 01/4 (25%) 1
    Musculoskeletal and connective tissue disorder - Other, specify1/3 (33.3%) 10/3 (0%) 00/4 (0%) 0
    Myalgia0/3 (0%) 00/3 (0%) 01/4 (25%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumor pain1/3 (33.3%) 10/3 (0%) 00/4 (0%) 0
    Nervous system disorders
    Dizziness1/3 (33.3%) 11/3 (33.3%) 32/4 (50%) 7
    Dysgeusia0/3 (0%) 02/3 (66.7%) 21/4 (25%) 1
    Headache0/3 (0%) 00/3 (0%) 03/4 (75%) 4
    Syncope0/3 (0%) 00/3 (0%) 01/4 (25%) 1
    Presyncope0/3 (0%) 00/3 (0%) 01/4 (25%) 1
    Psychiatric disorders
    Hallucinations0/3 (0%) 01/3 (33.3%) 11/4 (25%) 1
    Anxiety0/3 (0%) 01/3 (33.3%) 10/4 (0%) 0
    Insomnia0/3 (0%) 00/3 (0%) 01/4 (25%) 2
    Renal and urinary disorders
    Acute kidney injury0/3 (0%) 01/3 (33.3%) 11/4 (25%) 2
    Chronic kidney disease0/3 (0%) 01/3 (33.3%) 11/4 (25%) 2
    Hematuria1/3 (33.3%) 11/3 (33.3%) 10/4 (0%) 0
    Urinary incontinence1/3 (33.3%) 11/3 (33.3%) 10/4 (0%) 0
    Renal and urinary disorders - Other, specify0/3 (0%) 00/3 (0%) 01/4 (25%) 1
    Urinary frequency0/3 (0%) 00/3 (0%) 01/4 (25%) 1
    Urinary retention0/3 (0%) 01/3 (33.3%) 10/4 (0%) 0
    Urinary tract obstruction1/3 (33.3%) 10/3 (0%) 00/4 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnea1/3 (33.3%) 11/3 (33.3%) 11/4 (25%) 4
    Atelectasis0/3 (0%) 01/3 (33.3%) 10/4 (0%) 0
    Cough1/3 (33.3%) 10/3 (0%) 00/4 (0%) 0
    Epistaxis0/3 (0%) 01/3 (33.3%) 20/4 (0%) 0
    Skin and subcutaneous tissue disorders
    Alopecia0/3 (0%) 00/3 (0%) 01/4 (25%) 1
    Photosensitivity0/3 (0%) 01/3 (33.3%) 10/4 (0%) 0
    Vascular disorders
    Hypotension0/3 (0%) 01/3 (33.3%) 12/4 (50%) 3
    Hypertension0/3 (0%) 02/3 (66.7%) 40/4 (0%) 0
    Hot flashes0/3 (0%) 01/3 (33.3%) 10/4 (0%) 0
    Superficial thrombophlebitis0/3 (0%) 00/3 (0%) 01/4 (25%) 2
    Thromboembolic event1/3 (33.3%) 20/3 (0%) 00/4 (0%) 0

    Limitations/Caveats

    This study did not meet the anticipated accrual goal of 24 participants.

    More Information

    Certain Agreements

    Principal Investigators are NOT 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. Jingsong Zhang
    OrganizationH. Lee Moffitt Cancer Center and Research Institute
    Phone813-745-3973
    Emailjingsong.zhang@moffitt.org
    Responsible Party:
    H. Lee Moffitt Cancer Center and Research Institute
    ClinicalTrials.gov Identifier:
    NCT02300610
    Other Study ID Numbers:
    • MCC-17924
    First Posted:
    Nov 25, 2014
    Last Update Posted:
    Aug 1, 2019
    Last Verified:
    Jun 1, 2019