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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

Primary Purpose

Non-Muscle Invasive Bladder Cancer (NMIBC)

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Bacillus Calmette-Guérin (BCG)
Gemcitabine
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-Muscle Invasive Bladder Cancer (NMIBC) focused on measuring Bacillus Calmette-Guérin (BCG), Gemcitabine, 19-374

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Recurrent high-grade NMIBC Tis (with TaHG, or T1 also acceptable) 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

Sites / Locations

  • Hartford Healthcare (Data Collection)Recruiting
  • Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)Recruiting
  • Memorial Sloan Kettering Monmouth (Limited Protocol Activities)Recruiting
  • Memorial Sloan Kettering Bergen (Limited Protocol Activities)Recruiting
  • Memorial Sloan Kettering Commack (Limited Protocol Activities)Recruiting
  • Memorial Sloan Kettering Westchester (Limited Protocol Activities)Recruiting
  • Memorial Sloan Kettering Cancer Center (All Protocol Activities)Recruiting
  • Memorial Sloan Kettering Nassau (Limited Protocol Activities)Recruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Bacillus Calmette-Guérin (BCG) and Gemcitabine

Arm Description

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.

Outcomes

Primary Outcome Measures

evaluate the MTD (Phase I)
Describe the toxicities by frequency and by grade.This study will use CTCAE version 5.0 for toxicity and serious adverse event reporting.
proportion of patients who are disease free
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).

Secondary Outcome Measures

Full Information

First Posted
November 25, 2019
Last Updated
March 10, 2023
Sponsor
Memorial Sloan Kettering Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT04179162
Brief Title
Bacillus Calmette-Guérin (BCG) and Gemcitabine in People With High-Grade Non-Muscle Invasive Bladder Cancer That Came Back After BCG 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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 22, 2019 (Actual)
Primary Completion Date
November 2023 (Anticipated)
Study Completion Date
November 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center

4. Oversight

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

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Muscle Invasive Bladder Cancer (NMIBC)
Keywords
Bacillus Calmette-Guérin (BCG), Gemcitabine, 19-374

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
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)
Allocation
N/A
Enrollment
68 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Bacillus Calmette-Guérin (BCG) and Gemcitabine
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Bacillus Calmette-Guérin (BCG)
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Intervention Description
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 Measure Information:
Title
evaluate the MTD (Phase I)
Description
Describe the toxicities by frequency and by grade.This study will use CTCAE version 5.0 for toxicity and serious adverse event reporting.
Time Frame
1 year
Title
proportion of patients who are disease free
Description
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).
Time Frame
6 months after the start of treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Recurrent high-grade NMIBC Tis (with TaHG, or T1 also acceptable) 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Eugene Pietzak, MD
Phone
646-422-4781
Email
pietzake@mskcc.org
First Name & Middle Initial & Last Name or Official Title & Degree
Guido Dalbagni, MD
Phone
1-646-422-4394
Email
dalbagng@mskcc.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eugene Pietzak, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hartford Healthcare (Data Collection)
City
Hartford
State/Province
Connecticut
ZIP/Postal Code
06102
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anoop Meraney, MD
Phone
860-947-8500
Facility Name
Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
City
Basking Ridge
State/Province
New Jersey
ZIP/Postal Code
07920
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eugene Pietzak, MD
Phone
646-422-4781
Facility Name
Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
City
Middletown
State/Province
New Jersey
ZIP/Postal Code
07748
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eugene Pietzak, MD
Phone
646-422-4781
Facility Name
Memorial Sloan Kettering Bergen (Limited Protocol Activities)
City
Montvale
State/Province
New Jersey
ZIP/Postal Code
07645
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eugene Pietzak, MD
Phone
646-422-4781
Facility Name
Memorial Sloan Kettering Commack (Limited Protocol Activities)
City
Commack
State/Province
New York
ZIP/Postal Code
11725
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eugene Pietzak,, PhD
Phone
646-422-4781
Facility Name
Memorial Sloan Kettering Westchester (Limited Protocol Activities)
City
Harrison
State/Province
New York
ZIP/Postal Code
10604
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eugene Pietzak, MD
Phone
646-422-4781
Facility Name
Memorial Sloan Kettering Cancer Center (All Protocol Activities)
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eugene Pietzak, MD
Phone
646-422-4781
First Name & Middle Initial & Last Name & Degree
Anisha Augustin
Phone
646-422-4781
Email
augustia@mskcc.org
First Name & Middle Initial & Last Name & Degree
Eugene Pietzak, MD
Facility Name
Memorial Sloan Kettering Nassau (Limited Protocol Activities)
City
Uniondale
State/Province
New York
ZIP/Postal Code
11553
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eugene Pietzak, MD
Phone
646-422-4781

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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 clinicaltrials.gov 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: crdatashare@mskcc.org.
Links:
URL
http://www.mskcc.org/mskcc/html/44.cfm
Description
Memorial Sloan Kettering Cancer Center

Learn more about this trial

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

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