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

• ClinicalTrials.gov Identifier: NCT04386746
• Recruitment Status: Active, not recruiting
• First Posted: May 13, 2020
• Last Update Posted: January 9, 2023
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Information provided by (Responsible Party): Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Urothelial Carcinoma Bladder; Bladder Cancer	Drug: Gemcitabine; Drug: Docetaxel	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 26 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: July 29, 2020
• Actual Primary Completion Date: October 4, 2022
• Estimated Study Completion Date: June 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Intravesical Gemcitabine/Docetaxel	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

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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.
2. 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.
3. 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).
4. 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).

Other Outcome Measures:

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.
16. 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.
17. 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.
18. 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.
19. 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.
20. 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.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Maryland

Johns Hopkins University: Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, United States, 21287

Sponsors and Collaborators

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Investigators

• Principal Investigator: Max Kates, MD; Johns Hopkins University

More Information

Additional Information:

Sidney Kimmel Comprehensive Cancer Center website 

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT04386746
• Other Study ID Numbers: J2020; IRB00241941 ( Other Identifier: Johns Hopkins Institutional Review Boards )
• First Posted: May 13, 2020
• Last Update Posted: January 9, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:

NMIBC

Additional relevant MeSH terms:

Carcinoma; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urinary Bladder Diseases; Urologic Diseases; Gemcitabine; Docetaxel; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators