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

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT04386746

Collaborator

(none)

Enrollment

Location

Arm

46.1

Anticipated Duration (Months)

0.6

Patients Per Site Per Month

Study Details

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

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 :

Jul 29, 2020

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Jun 1, 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 Names: 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 Names: Taxotere

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 Names:

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 Names:

Taxotere

Outcome Measures

Primary Outcome Measures

3-Month Complete Response Rate [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

12-Month Relapse-Free Survival Rate [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 [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 [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 [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

Number of gene alterations as measured by RNA-seq [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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:
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)

Intermediate-risk tumors: All tumors not defined in the two adjacent categories (between the category of low- and high-risk)
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)

Note #1: Low-risk tumors as defined above are not eligible
Note #2: Mixed histologies are permitted, provided a component of urothelial carcinoma is present
Note #3: All patients with high-grade T1 (HGT1) should undergo a restaging TURBT
Eastern Cooperative Oncology Group (ECOG) (WHO) performance status 0, 1, or 2
Age ≥ 18 years old at time of consent
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:
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).
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).
Subjects who give a written informed consent obtained according to local guidelines.

Exclusion Criteria:

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

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.

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.
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.
Subjects who have had radiotherapy ≤ 4 weeks prior to starting study drug, or who have not recovered from radiotherapy toxicities.
Pregnant or breast-feeding women.
Subjects unwilling or unable to comply with the protocol.
Patients with prior systemic gemcitabine or docetaxel use for a non-bladder malignancy may enroll and receive treatment.