Enzalutamide in Combination With Gemcitabine and Cisplatin in Bladder Cancer

NCT02300610 | Completed Phase 1 Results FDA Drug

• 1 other identifier: MCC-17924
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

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.

Conditions

Bladder Cancer; Carcinoma, Transitional Cell; Renal Pelvis Cancer; Ureter Cancer; Urethra Cancer

Keywords

Ureteral Diseases; Urinary Bladder Diseases; Transitional Cell Carcinoma; Bladder; Carcinoma; Renal; Pelvis; Ureter; Urethra

Outcome Measures

Primary Outcomes (1)

• Recommended Dose of Enzalutamide

  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.

  Up to 6 months

Secondary Outcomes (3)

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

  Up to 6 months

• Progression Free Survival (PFS)

  14 months

• Overall Survival (OS)

  Up to 24 Months

Study Arms (2)

Dose Escalation

EXPERIMENTAL

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

Drug: Enzalutamide; Drug: Cisplatin; Drug: Gemcitabine

Dose Expansion

EXPERIMENTAL

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

Drug: Enzalutamide; Drug: Cisplatin; Drug: Gemcitabine

Interventions

Enzalutamide DRUG

Enzalutamide orally once a day. Dose Escalation Level 1: 80 mg; Level 2: 160 mg. Dose Expansion at recommended dose level, after dose escalation.

Also known as: MDV3100, XTANDI®

Dose Escalation; Dose Expansion

Cisplatin DRUG

Cisplatin at 70 mg/m\^2 IV on day 1, repeated every 21 days for total of 6 cycles.

Also known as: Platinol®, Platinol®-AQ

Dose Escalation; Dose Expansion

Gemcitabine DRUG

Gemcitabine at 1000 mg/m\^2 IV on days 1, 8, repeated every 21 days for total of 6 cycles.

Also known as: Gemzar ®

Dose Escalation; Dose Expansion

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead

Study Sites (2)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

University of Minnesota, Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Ureteral Neoplasms; Urethral Neoplasms; Ureteral Diseases; Urinary Bladder Diseases; Carcinoma

Interventions

enzalutamide; Cisplatin; Gemcitabine

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urologic Diseases; Male Urogenital Diseases; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Urethral Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Limitations and Caveats

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

Results Point of Contact

• Title: Dr. Jingsong Zhang
• Organization: H. Lee Moffitt Cancer Center and Research Institute

jingsong.zhang@moffitt.org

813-745-3973

Study Officials

• Jingsong Zhang, M.D., Ph.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

• Shilpa Gupta, M.D.

  University of Minnesota Masonic Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2014
• First Posted: November 25, 2014
• Study Start: February 11, 2015
• Primary Completion: August 7, 2017
• Study Completion: April 19, 2019
• Last Updated: August 1, 2019
• Results First Posted: August 1, 2019

Record last verified: 2019-06

Locations

US (2)