Neoadjuvant Gemcitabine and Fractionated, Weekly Cisplatin For Muscle Invasive Bladder Cancer and Patients Not Candidates For High Dose Cisplatin

This study has been terminated.
(The study is being closed to accrual secondary to low accrual and an interest in opening up a different trial.)
Information provided by (Responsible Party):
Jodi Layton, Brown University Identifier:
First received: December 20, 2013
Last updated: February 25, 2016
Last verified: February 2016

The standard treatment of muscle invasive bladder cancer is to administer chemotherapy for approximately 3 months then to have surgery to remove the bladder. Chemotherapy may reduce the size of the cancer in your bladder before surgery and can also help to reduce the chance that your bladder cancer will come back (metastasize) in other parts of your body after bladder surgery.

This study will involve testing cisplatin in lower weekly doses with gemcitabine.The purpose of this study is to test the effects, good and bad, of low dose weekly cisplatin and gemcitabine.

Condition Intervention Phase
Invasive Bladder Cancer
Bladder Cancer
Drug: Gemcitabine and fractionated cisplatin (combination treatment)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: BrUOG 300: Neoadjuvant Gemcitabine and Fractionated, Weekly Cisplatin For Muscle Invasive Bladder Cancer and Patients Not Candidates For High Dose Cisplatin

Resource links provided by NLM:

Further study details as provided by Brown University:

Primary Outcome Measures:
  • Pathologic Complete Response Rate of Neoadjuvant Gemcitabine and Fractionated Cisplatin for Patients With Muscle Invasive Bladder Cancer Whom Are Not Candidates for High Dose Cisplatin. [ Time Frame: at approximately 6 months ] [ Designated as safety issue: No ]
    Response will be evaluated in this study using the international criteria proposed in the Revised Response Evaluation Criteria in Solid Tumors (RECIST) Guideline version 1.1 [Eur J Cancer. 2009;45:228-247.].Complete Response (CR): Disappearance of all target lesions; Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of 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). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficie

Secondary Outcome Measures:
  • Toxicities Participants Experience With Neoadjuvant Gemcitabine and Fractionated Cisplatin for Patients With Bladder Cancer. [ Time Frame: Prior to each of the 4 cycles of treatment, after 4 months of treatment, 30 days post the last dose of drug (for a total of approximately 5 months) ] [ Designated as safety issue: Yes ]
    Toxicities assessed while patients are on treatments

Enrollment: 2
Study Start Date: July 2014
Study Completion Date: June 2015
Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Gemcitabine and fractionated cisplatin (combination treatment)
1 Cycle = 21 days. GC x 4 cycles ----> cystectomy Gemcitabine: 1000mg/m2, days 1 and 8 Cisplatin: 35mg/m2, days 1 and 8
Drug: Gemcitabine and fractionated cisplatin (combination treatment)
1 Cycle = 21 days. GC x 4 cycles ----> cystectomy Gemcitabine: 1000mg/m2, days 1 and 8 Cisplatin: 35mg/m2, days 1 and 8


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Pathologically confirmed muscle-invasive urothelial (transitional cell) carcinoma of the bladder or upper genitourinary tract.
  2. Stage T2-T4a. Patients may have nodal disease but there must be no evidence of distant metastases and patients must be candidates for radical cystectomy as determined by urologic surgeon (note from/confirmation by surgeon required).
  3. No prior systemic therapy for urothelial carcinoma. Prior intravesical therapy is allowed.
  4. Patients are determined by their treating oncologist to not be a candidate high dose cisplatin (> 70mg/m2) due to medical comorbidities.
  5. Creatinine Clearance (CrCL or eCCr)) > 25 mL/min calculated using the Cockcroft-Gault formula
  6. Patients without serious medical risk factors involving any of the major organ systems such that the investigator considers it unsafe for the patient to receive the protocol treatment of this study with gemcitabine and weekly fractionated cisplatin.
  7. Preexisting neuropathy < grade 2.
  8. No prior invasive malignancy within the prior two years. However, prior history of non-muscle invasive bladder cancer and patients with an early stage malignancy that is not expected to require treatment in the next 2 years (such as early stage, resected breast cancer, or asymptomatic prostate cancer) are eligible.
  9. ECOG performance status 0 or 1.
  10. Age ≥ 18 years of age.
  11. Not pregnant and not nursing. Women of child bearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 7 days prior to beginning of treatment. Post-menopausal women (surgical menopause or lack of menses >12 months) do not need to have a pregnancy test, please document status.
  12. Required Initial Laboratory Values:

    • Neutrophils ≥ 1,000/μl
    • Platelet count ≥ 100,000/μl
    • Total bilirubin ≤ 1.5 x ULN.
    • AST (SGOT) & ALT (SGPT) ≤ 3.0 x ULN

Exclusion Criteria:

  1. Metastatic disease.
  2. Prior hypersensitivity to platinums that in the investigators opinion would put the patient at risk if re-exposed
  3. Small cell cancer of the bladder or pure adenocarcinoma. Patients with mixed histologies such as urothelial carcinoma with sarcomatoid features, squamous differentiation or adenocarcinoma are allowed as long as transitional cell cancer is the predominant pathologic subtype.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT02030574

United States, Rhode Island
Rhode Island Hospital (including Newport Hospital and East Greenwich)
Providence, Rhode Island, United States, 02903
The Miriam Hospital
Providence, Rhode Island, United States, 02906
Sponsors and Collaborators
Brown University
  More Information

Responsible Party: Jodi Layton, Principal Investigator, Brown University Identifier: NCT02030574     History of Changes
Other Study ID Numbers: BrUOG 300 
Study First Received: December 20, 2013
Results First Received: October 27, 2015
Last Updated: February 25, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms
Anti-Infective Agents
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs processed this record on May 25, 2016