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Intravesical Gemcitabine and Docetaxel for BCG naïve Non-muscle Invasive Bladder Cancer (GEMDOCE)

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ClinicalTrials.gov Identifier: NCT04386746
Recruitment Status : Recruiting
First Posted : May 13, 2020
Last Update Posted : August 4, 2020
Sponsor:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Tracking Information
First Submitted Date  ICMJE May 8, 2020
First Posted Date  ICMJE May 13, 2020
Last Update Posted Date August 4, 2020
Actual Study Start Date  ICMJE July 29, 2020
Estimated Primary Completion Date August 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 8, 2020)
3-Month Complete Response Rate [ Time Frame: 3 months ]
Proportion of patients with no evidence of recurrent high grade urothelial carcinoma of the bladder of any stage as assessed by cystoscopy with biopsy and urine cytology.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 8, 2020)
  • 12-Month Relapse-Free Survival Rate [ Time Frame: 12 months ]
    Proportion of patients alive and with no evidence of recurrent high grade urothelial carcinoma of the bladder of any stage.
  • 24-Month Relapse-Free Survival Rate [ Time Frame: 24 months ]
    Proportion of patients alive and with no evidence of recurrent high grade urothelial carcinoma of the bladder of any stage.
  • Safety profile as assessed by proportion of adverse events by type [ Time Frame: Up to 24 months ]
    Proportion of adverse events by type, as defined by Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0).
  • Safety profile as assessed by proportion of adverse events by grade [ Time Frame: Up to 24 months ]
    Proportion of adverse events by grade, as defined by Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: May 8, 2020)
  • Number of gene alterations as measured by RNA-seq [ Time Frame: 3 months ]
    Number of gene alterations as measured by RNA-seq. Compare results to 3-month Complete Response rate using statistical methods.
  • Type of gene alterations as measured by RNA-seq [ Time Frame: 3 months ]
    Type of gene alterations as measured by RNA-seq. Compare results to 3-month Complete Response rate using statistical methods.
  • Number of gene alterations as measured by RNA-seq [ Time Frame: 12 months ]
    Number of gene alterations as measured by RNA-seq. Compare results to 12-month Relapse-Free Survival rate using statistical methods.
  • Type of gene alterations as measured by RNA-seq [ Time Frame: 12 months ]
    Type of gene alterations as measured by RNA-seq. Compare results to 12-month Relapse-Free Survival rate using statistical methods.
  • Number of DNA mutations as measured by whole transcriptome [ Time Frame: 3 months ]
    Number of DNA mutations as measured by whole transcriptome. Compare results to 3-month Complete Response rate.
  • Number of DNA mutations as measured by whole exome [ Time Frame: 3 months ]
    Number of DNA mutations as measured by whole exome. Compare results to 3-month Complete Response rate.
  • Number of DNA mutations as measured by panel DNA sequencing [ Time Frame: 3 months ]
    Number of DNA mutations as measured by panel DNA sequencing. Compare results to 3-month Complete Response rate.
  • Type of DNA mutations as measured by whole transcriptome [ Time Frame: 3 months ]
    Type of DNA mutations as measured by whole transcriptome. Compare results to 3-month Complete Response rate.
  • Type of DNA mutations as measured by whole exome [ Time Frame: 3 months ]
    Type of DNA mutations as measured by whole exome. Compare results to 3-month Complete Response rate.
  • Type of DNA mutations as measured by panel DNA sequencing [ Time Frame: 3 months ]
    Type of DNA mutations as measured by panel DNA sequencing. Compare results to 3-month Complete Response rate.
  • Number of DNA mutations as measured by whole transcriptome [ Time Frame: 12 months ]
    Number of DNA mutations as measured by whole transcriptome. Compare results to 12-month Relapse Free Survival rate using statistical analysis.
  • Number of DNA mutations as measured by whole exome [ Time Frame: 12 months ]
    Number of DNA mutations as measured by whole exome. Compare results to 12-month Relapse Free Survival rate using statistical analysis.
  • Number of DNA mutations as measured by panel DNA sequencing [ Time Frame: 12 months ]
    Number of DNA mutations as measured by panel DNA sequencing. Compare results to 12-month Relapse Free Survival rate using statistical analysis.
  • Type of DNA mutations as measured by whole transcriptome [ Time Frame: 12 months ]
    Type of DNA mutations as measured by whole transcriptome. Compare results to 12-month Relapse Free Survival rate using statistical analysis.
  • Type of DNA mutations as measured by whole exome [ Time Frame: 12 months ]
    Type of DNA mutations as measured by whole exome. Compare results to 12-month Relapse Free Survival rate using statistical analysis.
  • Type of DNA mutations as measured by panel DNA sequencing [ Time Frame: 12 months ]
    Type of DNA mutations as measured by panel DNA sequencing. Compare results to 12-month Relapse Free Survival rate using statistical analysis.
  • Numbers of t-cell subpopulations [ Time Frame: 3 months ]
    Numbers of t-cell subpopulations utilizing immunohistochemical (IHC) staining and flow cytometry. Compare results to 3-month Complete Response rate using statistical analysis.
  • Ratio of t-cell subpopulations [ Time Frame: 3 months ]
    Ratio of t-cell subpopulations utilizing IHC staining and flow cytometry. Compare results to 3-month Complete Response rate using statistical analysis.
  • Numbers of t-cell subpopulations [ Time Frame: 12-months ]
    Numbers of t-cell subpopulations utilizing IHC staining and flow cytometry. Compare results to 12-month Relapse-Free Survival rate using statistical analysis.
  • Ratio of t-cell subpopulations [ Time Frame: 12-months ]
    Ratio of t-cell subpopulations utilizing IHC staining and flow cytometry. Compare results to 12-month Relapse-Free Survival rate using statistical analysis.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Intravesical Gemcitabine and Docetaxel for BCG naïve Non-muscle Invasive Bladder Cancer
Official Title  ICMJE A Phase II Trial for the Use of Intravesical Gemcitabine and Docetaxel (GEMDOCE) in the Treatment of BCG naïve Non-muscle Invasive Urothelial Carcinoma of the Bladder
Brief Summary A single-arm, two-stage, open-label, phase 2 study investigating the safety and efficacy of intravesical gemcitabine/docetaxel for bacillus Calmette-Guerin (BCG)-naïve patients with non-muscle invasive bladder cancer (NMIBC). All participants will receive an induction course of gemcitabine/docetaxel instillations followed by maintenance instillations if initial efficacy is seen. In addition to providing initial efficacy data, this study will provide safety and long-term efficacy data on the combination regimen studied. A tolerable safety profile and demonstrated efficacy would support a potential, randomized phase 3 trial comparing the experimental combination therapy and standard of care intravesical BCG therapy.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Urothelial Carcinoma Bladder
  • Bladder Cancer
Intervention  ICMJE
  • Drug: Gemcitabine
    1g gemcitabine in 50ml sterile water; instilled once weekly for 6 weeks and then once monthly for ≤ 21 months.
    Other Name: Gemzar
  • Drug: Docetaxel
    37.5mg docetaxel in 50ml normal saline solution (NSS); instilled once weekly for 6 weeks and then once monthly for ≤ 21 months.
    Other Name: Taxotere
Study Arms  ICMJE Experimental: Intravesical Gemcitabine/Docetaxel
Interventions:
  • Drug: Gemcitabine
  • Drug: Docetaxel
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 8, 2020)
26
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2024
Estimated Primary Completion Date August 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Histologically confirmed intermediate or high-risk non-muscle invasive urothelial carcinoma of the bladder (Ta, T1, or Tis stage) on TURBT obtained within 90 days of registration defined according to modified EORTC risk criteria summarized as follows:

    1. Low-risk tumors: Initial or recurrent tumor > 12 months after resection with all of the following:

      • Solitary tumor
      • Low-grade
      • < 3 cm
      • No carcinoma in situ (CIS)
    2. Intermediate-risk tumors: All tumors not defined in the two adjacent categories (between the category of low- and high-risk)
    3. High-risk tumors: Any of the following:

      • T1 tumor
      • High-grade
      • CIS
      • Multiple and recurrent and large (> 3 cm) Ta low-grade tumors (all conditions must be met for this point of Ta low-grade tumors)
    4. Note #1: Low-risk tumors as defined above are not eligible
    5. Note #2: Mixed histologies are permitted, provided a component of urothelial carcinoma is present
    6. Note #3: All patients with high-grade T1 (HGT1) should undergo a restaging TURBT
  2. Eastern Cooperative Oncology Group (ECOG) (WHO) performance status 0, 1, or 2
  3. Age ≥ 18 years old at time of consent
  4. Evidence of post-menopausal status or negative urinary or serum pregnancy test or female pre-menopausal patients is required. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:

    1. Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
    2. Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
  5. Subjects who give a written informed consent obtained according to local guidelines.

Exclusion Criteria:

  1. Subjects with muscle-invasive (i.e. T2, T3, T4), locally advanced unresectable, or metastatic urothelial carcinoma as assessed on baseline radiographic imaging obtained within 90 days prior to study registration. The required radiographic imaging includes:

    1. Abdomen/Pelvis - CT scan
    2. Chest - chest x-ray or CT scan
  2. Subjects with concurrent upper urinary tract (i.e. ureter, renal pelvis) urothelial carcinoma of any stage.

    a. Note: Subjects with history of non-invasive (Ta, Tis) upper tract urothelial carcinoma that has been definitively treated with at least one post-treatment disease assessment (i.e. cytology, biopsy, imaging) that demonstrates no evidence of residual disease are eligible.

  3. Subjects with another active second malignancy with an estimated overall survival from the second malignancy of < 12 months. Subjects with another second active malignancy that are deemed to have an estimated overall survival of >12 months are eligible.
  4. Subjects who have received the last administration of an anti-cancer therapy including chemotherapy, immunotherapy, and monoclonal antibodies ≤ 4 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy.
  5. Subjects who have had radiotherapy ≤ 4 weeks prior to starting study drug, or who have not recovered from radiotherapy toxicities.
  6. Pregnant or breast-feeding women.
  7. Subjects unwilling or unable to comply with the protocol.
  8. Patients with prior systemic gemcitabine or docetaxel use for a non-bladder malignancy may enroll and receive treatment.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Max Kates, MD 4106140009 mkates@jhmi.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04386746
Other Study ID Numbers  ICMJE J2020
IRB00241941 ( Other Identifier: Johns Hopkins Institutional Review Boards )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
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.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study Sponsor  ICMJE Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Max Kates, MD Johns Hopkins University
PRS Account Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP