Intravesical Cabazitaxel, Gemcitabine, and Cisplatin (CGC) in the Treatment Urothelial Carcinoma of the Bladder

NCT02202772 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: AAAM8506
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators intend to evaluate the safety and toxicity profile of intravesically administered multidrug regimen of Cabazitaxel, Cisplatin and Gemcitabine in treatment refractory Transitional Cell Carcinoma.The investigators propose to conduct a combined phase I trial to assess the safety, toxicity, and efficacy of a novel multidrug intravesical regimen consisting of Cabazitaxel, Gemcitabine, and Cisplatin (CGC) in the treatment of BCG resistant non-muscle invasive urothelial carcinoma of the bladder. This phase I trial will have a combined dose and cycle-escalation scheme with enrollment of up to 24 patients.

Conditions

Urothelial Carcinoma of the Urinary Bladder

Keywords

Urothelial; Cisplatin; Gemcitabine; Cabazitaxel; Bladder; Carcinoma; Bacillus Calmette-Guerin; Intravesical; Recurrent; Non-muscle; Invasive; Cancer

Outcome Measures

Primary Outcomes (2)

• Phase 1a/1b: The number of serious adverse events associated with therapy of intravesically administered Cabazitaxel, Gemcitabine, and Cisplatin.

  The investigator is measuring safety by looking at the number of events that occur during the study

  6 weeks from baseline

• Phase 2: The number of complete responders after completion of six weeks of intravesically

  The investigator is measuring efficacy by the number of complete responders to the treatment

  6 weeks from baseline

Study Arms (5)

Gem and Low Cab

EXPERIMENTAL

Gemcitabine: Intravesical; 2000mg/100ml; 1 time a week for 6 weeks; 2 hours Cabazitaxel: Intravesical; 2.5mg/100ml; 1 time a week for 6 weeks; 2 hours

Drug: Cabazitaxel; Drug: Gemcitabine

Gem and High Cab

EXPERIMENTAL

Gemcitabine: Intravesical; 2000mg/100ml; 1 time a week for 6 weeks; 2 hours Cabazitaxel: Intravesical; 5mg/100ml; 1 time a week for 6 weeks; 2 hours

Drug: Cabazitaxel; Drug: Gemcitabine

Gem, High Cab, and Low Cis

EXPERIMENTAL

Gemcitabine: Intravesical; 2000mg/100ml; 1 time a week for 6 weeks; 2 hours Cabazitaxel: Intravesical; 5mg/100ml; 1 time a week for 6 weeks; 2 hours Cisplatin: Intravesical; 66mg/100ml; 1 time a week for 6 weeks; 2 hours

Drug: Cabazitaxel; Drug: Gemcitabine; Drug: Cisplatin

Gem, High Cab, Mod Cis

EXPERIMENTAL

Gemcitabine: Intravesical; 2000mg/100ml; 1 time a week for 6 weeks; 2 hours Cabazitaxel: Intravesical; 5mg/100ml; 1 time a week for 6 weeks; 2 hours Cisplatin: Intravesical; 80mg/100ml; 1 time a week for 6 weeks; 2 hours

Drug: Cabazitaxel; Drug: Gemcitabine; Drug: Cisplatin

Gem, High Cab, High Cis

EXPERIMENTAL

Gemcitabine: Intravesical; 2000mg/100ml; 1 time a week for 6 weeks; 2 hours Cabazitaxel: Intravesical; 5mg/100ml; 1 time a week for 6 weeks; 2 hours Cisplatin: Intravesical; 100mg/100ml; 1 time a week for 6 weeks; 2 hours

Drug: Cabazitaxel; Drug: Gemcitabine; Drug: Cisplatin

Interventions

Cabazitaxel DRUG

Intravesical instillation of the Cabazitaxel for 2 hours

Also known as: Jevtana

Gem and High Cab; Gem and Low Cab; Gem, High Cab, High Cis; Gem, High Cab, Mod Cis; Gem, High Cab, and Low Cis

Gemcitabine DRUG

Intravesical instillation of Gemcitabine for 2 hours

Also known as: Gemzar

Gem and High Cab; Gem and Low Cab; Gem, High Cab, High Cis; Gem, High Cab, Mod Cis; Gem, High Cab, and Low Cis

Cisplatin DRUG

Intravesical installation of Cisplatin for 2hours

Also known as: Platinol, Platinol-AQ

Gem, High Cab, High Cis; Gem, High Cab, Mod Cis; Gem, High Cab, and Low Cis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have a histologically confirmed diagnosis of non- muscle invasive urothelial carcinoma of the bladder at the study institution prior to the beginning of the study. This includes patients with:
• High grade Ta papillary lesion(s)
• High or low grade T1 papillary lesion(s)
• Carcinoma In Situ (CIS), with or without Ta or T1 papillary tumor(s) of any grade The patient must have Bacillus Calmette-Guerin (BCG) refractory or recurrent non-muscle invasive bladder cancer
• Refractory disease is defined as evidence of persistent high risk bladder cancer (high grade Ta, T1 and/or CIS) at the first cystoscopic exam after the initial 6 week induction course of BCG or at the 6 month cystoscopic exam.
• Recurrent disease is defined as reappearance of disease after achieving a tumor- free status by 6 months following a full induction course of BCG with or without maintenance BCG. Participants must have recurred within 18 months following the last dose of BCG.
• Low-grade superficial (Ta) disease will not be considered recurrent.
• Patients must exhibit disease recurrence after receiving some form of standard intravesical therapy that must include a minimum of one induction course of BCG and may also include prior exposure to mitomycin, interferon, single agent gemcitabine or taxane therapy or maintenance.
• Patients must be eligible for radical cystectomy and refuse this standard of care treatment or not be a surgical candidate for radical cystectomy based on other comorbidities.
• All grossly visible disease in the bladder must be fully resected and pathologic stage will be confirmed at the study institution.
• Patients enrolled in other clinical trials must have received their last treatment at least 6 weeks prior to enrollment.
• Age \> 18 and must be able to read, understand and sign informed consent
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance Status: ECOG of 0 or 1 including patients who are not surgical candidates due to comorbid conditions.
• Women of childbearing potential must have a negative pregnancy test.
• All patients of childbearing potential must be willing to consent to using effective contraception, i.e., intrauterine device (IUD), Birth control pills, Depo-Provera, and condoms while on treatment and for 3 months after their participation in the study ends.

You may not qualify if:

• History of severe hypersensitivity reaction (≥grade 3) to docetaxel
• History of severe hypersensitivity reaction (≥grade 3) to polysorbate 80 containing drugs
• Concurrent or planned treatment with strong inhibitors or strong inducers of cytochrome P450 3A4/5 (a one week wash-out period is necessary for patients who are already on I these treatments)
• Concurrent malignancy diagnosed within 6 months of entry to the study.
• Concurrent treatment with any systemic chemotherapeutic agent.
• Inadequate organ and bone marrow function as evidenced by:
• Hemoglobin: less than 8.0 g/dL
• Absolute neutrophil count: less than 1.5 x 10\^9/L
• Platelet count: less than 80x 10\^9/L
• Aspartate Aminotransferase Test (AST) / Serum Glutamic Oxaloacetic Transaminase (SGOT) and/or ( Alanine Aminotransferase Test (ALT)/ Serum Glutamic Pyruvic Transaminase (SGPT) \>2.5 x upper limit of normal (ULN);
• Total bilirubin \>1.5 x ULN
• Serum creatinine \>2 x ULN. If creatinine 1.5 - 2.0 x ULN, creatinine clearance will be calculated according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula and patients with creatinine clearance \<30 mL/min should be excluded.
• Women who are pregnant or lactating.
• Documented history of vesicoureteral reflux or an indwelling urinary stent.
• Participation in any other research protocol involving administration of an investigational agent within 6 weeks prior to study entry.

Sponsors & Collaborators

• Guarionex J. Decastro: lead
• Sanofi: collaborator

Study Sites (1)

Columbia University Irving Medical Center - HIP

New York, New York, 10032, United States

Location

Related Links

• Columbia University current clinical trials

MeSH Terms

Conditions

Carcinoma; Recurrence; Neoplasms

Interventions

cabazitaxel; Gemcitabine; Cisplatin

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Guarionex DeCastro, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Urology at the Columbia University Medical

Study Record Dates

• First Submitted: July 25, 2014
• First Posted: July 29, 2014
• Study Start: December 1, 2014
• Primary Completion: April 1, 2026
• Study Completion (Estimated): April 1, 2028
• Last Updated: February 24, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)