Clinical Trials /

Enzalutamide in Combination With Gemcitabine and Cisplatin in Bladder Cancer

NCT02300610

Description:

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.

Related Conditions:
  • Bladder Carcinoma
  • Renal Pelvis and Ureter Carcinoma
  • Urethral Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Enzalutamide</span> in Combination With <span class="go-doc-concept go-doc-intervention">Gemcitabine and Cisplatin</span> in Bladder Cancer

Title

  • Brief Title: Enzalutamide in Combination With Gemcitabine and Cisplatin in Bladder Cancer
  • Official Title: A Phase I/1b Study of Enzalutamide in Combination With Gemcitabine and Cisplatin in Bladder Cancer
  • Clinical Trial IDs

    NCT ID: NCT02300610

    ORG ID: MCC-17924

    Trial Conditions

    Bladder Cancer

    Carcinoma, Transitional Cell

    Renal Pelvis Cancer

    Ureter Cancer

    Urethra Cancer

    Trial Interventions

    Drug Synonyms Arms
    Enzalutamide MDV3100, XTANDI Dose Escalation and Dose Expansion
    Cisplatin Platinol, Platinol-AQ Dose Escalation and Dose Expansion
    Gemcitabine Gemzar Dose Escalation and Dose Expansion

    Trial Purpose

    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.

    Trial Arms

    Name Type Description Interventions
    Dose Escalation and Dose Expansion Experimental Dose Escalation: Begin with Level 1 dose of 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. Enzalutamide, Cisplatin, Gemcitabine

    Eligibility Criteria

    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)

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Maximum Tolerated Dose (MTD)

    Secondary Outcome Measures

    Overall Response Rate (ORR): Complete Response (CR) + Partial Response (PR)

    Progression Free Survival (PFS)

    Overall Survival (OS)

    Trial Keywords

    Ureteral Diseases

    Urinary Bladder Diseases

    Transitional Cell Carcinoma

    Bladder

    Carcinoma

    Renal

    Pelvis

    Ureter

    Urethra