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Bacillus Calmette-Guérin (BCG) and Gemcitabine in People With High-Grade Non-Muscle Invasive Bladder Cancer That Came Back After BCG Treatment

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04179162
Recruitment Status : Recruiting
First Posted : November 27, 2019
Last Update Posted : March 18, 2021
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Brief Summary:
This study will test the safety of BCG and gemcitabine in people who have BCG-relapsing Non-Muscle Invasive Bladder Cancer (NMIBC). The researchers will test increasing doses of gemcitabine to find the highest dose that causes few or mild side effects when combined with BCG. The study will also look at whether this combination of drugs is effective in treating BCG-relapsing NMIBC.

Condition or disease Intervention/treatment Phase
Non-Muscle Invasive Bladder Cancer (NMIBC) Drug: Bacillus Calmette-Guérin (BCG) Drug: Gemcitabine Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 68 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: This is a phase I/II trial of intravesical gemcitabine given between doses of BCG in patients who have relapsing but BCG-responsiveNon-Muscle Invasive Bladder Cancer (NMIBC).
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Trial of Bacillus Calmette-Guérin (BCG) and Intravesical Gemcitabine for Patients With BCG-Relapsing High-Grade Non-Muscle Invasive Bladder Cancer
Actual Study Start Date : November 22, 2019
Estimated Primary Completion Date : November 2022
Estimated Study Completion Date : November 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bladder Cancer

Arm Intervention/treatment
Experimental: Bacillus Calmette-Guérin (BCG) and Gemcitabine
Eligible patients will receive combination intravesical chemoimmunotherapy. Treatment is sequential, with twice-weekly intravesical gemcitabine given at weeks 1, 4, 7, and 10, for a total of 8 doses, administered in a standard fashion. In phase I, the dose of gemcitabine will depend on the dose level being assessed for the determination of the MTD. phase II, 1 dose level will be given (the MTD from phase I). Fixed doses of once-weekly intravesical BCG therapy (TICE strain, 50 mg) will be given at weeks 2 (+/- 2 days), 3 (+/- 2 days), 5 (+/- 2 days), 6 (+/- 2 days), 8 (+/- 2 days), and 9 (+/- 2 days), for a total of 6 doses, also administered in a standard fashion. All intravesical therapy will be administered in the chemotherapy suite on an outpatient basis, in accordance with standard clinical practice. Intravesical therapies will be retained in the bladder for up to 2 h (BCG) or 1 h (gemcitabine), or as tolerated.
Drug: Bacillus Calmette-Guérin (BCG)
Patients will receive once-weekly intravesical BCG therapy (TICE strain, 50 mg) at weeks 2 (+/- 2 days), 3 (+/- 2 days), 5 (+/- 2 days), 6(+/- 2 days), 8 (+/- 2 days), and 9 (+/- 2 days).

Drug: Gemcitabine
Patients will receive gemcitabine at their specified dose level, given in a twice weekly fashion, with 72 to 96 h (+/- 1 day) between doses, at weeks 1, 4, 7, and 10.

Primary Outcome Measures :
  1. evaluate the MTD (Phase I) [ Time Frame: 1 year ]
    Describe the toxicities by frequency and by grade.This study will use CTCAE version 5.0 for toxicity and serious adverse event reporting.

  2. proportion of patients who are disease free [ Time Frame: 6 months after the start of treatment ]
    Will be assessed by both urine cytology and cystoscopy at 6 months after initiation of therapy. Disease free (i.e., complete treatment response) is defined as no evidence of disease (negative cytology and cystoscopy).

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Recurrent high-grade NMIBC (Tis, TaHG, or T1) within 24 months of the last treatment with BCG (with or without IFN)
  • Pathologic confirmation of stage, grade, and urothelial histology by the Department of Pathology at MSK
  • All visible papillary lesions macroscopically resected within 60 days of treatment initiation
  • Absence of urothelial carcinoma involving the upper urinary tract (documented by radiological imaging or ureteroscopy) within 12 months from the start of treatment
  • Receipt of restaging transurethral resection (TUR) for any tumor with invasion into the lamina propria (HGT1) as part of standard care
  • Age ≥18 years
  • Karnofsky performance status ≥60%
  • Informed consent

Exclusion Criteria:

  • Positive pregnancy test
  • Known contraindications to BCG

    • History of systemic hypersensitivity reaction or history of febrile systemic BCG reaction
    • Febrile illness or persistent gross hematuria
    • Active tuberculosis
    • Immunosuppression due to congenital or acquired immune deficiency, concurrent immune suppressive disease, systemic cancer therapy, or chronic immunosuppressive therapy other than topical or inhaled corticosteroids
  • History of or currently being treated for muscle-invasive (i.e., stage T2 or higher) or metastatic urothelial cell carcinoma
  • Evidence of concurrent extravesical (i.e., urethra, ureter, or renal pelvis) urothelial cell carcinoma
  • BCG-unresponsive NMIBC as defined by the FDA:

    • HGT1 within 3 months after an induction BCG course (received ≥5 of 6 doses)
    • Persistent or recurrent high-grade NMIBC (Tis, Ta, T1) within 6 months of ≥5 of 6 doses of induction BCG therapy and ≥2 of 3 doses of maintenance BCG therapy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04179162

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Contact: Eugene Pietzak, MD 646-422-4781
Contact: Guido Dalbagni, MD 1-646-422-4394

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United States, Connecticut
Hartford Healthcare (Data Collection) Not yet recruiting
Hartford, Connecticut, United States, 06102
Contact: Anoop Meraney, MD    860-947-8500      
United States, New Jersey
Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities) Recruiting
Basking Ridge, New Jersey, United States, 07920
Contact: Eugene Pietzak, MD    646-422-4781      
Memorial Sloan Kettering Monmouth (Limited Protocol Activities) Recruiting
Middletown, New Jersey, United States, 07748
Contact: Eugene Pietzak, MD    646-422-4781      
Memorial Sloan Kettering Bergen (Limited Protocol Activities) Recruiting
Montvale, New Jersey, United States, 07645
Contact: Eugene Pietzak, MD    646-422-4781      
United States, New York
Memorial Sloan Kettering Commack (Limited Protocol Activities) Recruiting
Commack, New York, United States, 11725
Contact: Eugene Pietzak,, PhD    646-422-4781      
Memorial Sloan Kettering Westchester (Limited Protocol Activities) Recruiting
Harrison, New York, United States, 10604
Contact: Eugene Pietzak, MD    646-422-4781      
Memorial Sloan Kettering Cancer Center (All Protocol Activities) Recruiting
New York, New York, United States, 10065
Contact: Eugene Pietzak, MD    646-422-4781      
Contact: Anisha Augustin    646-422-4781   
Principal Investigator: Eugene Pietzak, MD         
Memorial Sloan Kettering Nassau (Limited Protocol Activities) Recruiting
Uniondale, New York, United States, 11553
Contact: Eugene Pietzak, MD    646-422-4781      
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
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Principal Investigator: Eugene Pietzak, MD Memorial Sloan Kettering Cancer Center
Additional Information:
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Responsible Party: Memorial Sloan Kettering Cancer Center Identifier: NCT04179162    
Other Study ID Numbers: 19-374
First Posted: November 27, 2019    Key Record Dates
Last Update Posted: March 18, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to:

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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 Memorial Sloan Kettering Cancer Center:
Bacillus Calmette-Guérin (BCG)
Additional relevant MeSH terms:
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Urinary Bladder Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
BCG Vaccine
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Adjuvants, Immunologic