Intravesical Cabazitaxel, Gemcitabine, and Cisplatin (CGC) in the Treatment Urothelial Carcinoma of the Bladder
Conditions
Urothelial Carcinoma of the Urinary Bladder
Conditions: official terms
Carcinoma - Carcinoma, Transitional Cell - Urinary Bladder Neoplasms
Conditions: Keywords
Urothelial, Cisplatin, Gemcitabine, Cabazitaxel, Bladder, Carcinoma, Bacillus Calmette-Guerin, Intravesical, Recurrent, Non-muscle, Invasive, Cancer
Study Type
Interventional
Study Phase
Phase 1
Study Design
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: Cabazitaxel Type: Drug
Name: Gemcitabine Type: Drug
Name: Cisplatin Type: Drug
Overall Status
Recruiting
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.
Detailed Description
Nonsurgical treatment strategies for BCG refractory bladder cancer have failed to prove themselves as reliable options for increased survival among this subset of bladder cancer patients. For these patients, removal of the bladder with all the associated perioperative risks and the subsequent reduction of quality of life, remains the only option. Prior attempts at second line treatments have included intravesical (within the bladder) monotherapy with a range of drugs including Gemcitabine and Paclitaxel (a taxane, similar to Cabazitaxel). These drugs have shown some potential improvement for a small number of patients Given the synergy of systemic chemotherapy, it is believed that a multidrug regimen would allow for further improvement in survival among these patients.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: Inclusion Criteria:

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 grade bladder cancer (Ta, T1 and/or CIS) at the first cystoscopic exam after the initial 6 week induction course of Bacillus Calmette-Guerin (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 Bacillus Calmette-Guerin (BCG) with or without maintenance Bacillus Calmette-Guerin (BCG). Participants must have recurred within 18 months following the last dose of Bacillus Calmette-Guerin (BCG).

o Patients must exhibit disease recurrence after receiving some form of standard intravesical therapy that must include a minimum of one induction course of Bacillus Calmette-Guerin (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: Eastern Cooperative Oncology Group (ECOG) of 0 or 1 (See Appendix I) including patients who are not surgical candidates due to comorbid conditions.

- Peripheral neuropathy: must be < grade 1

- 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., IUD, Birth control pills, Depo-Provera, and condoms while on treatment and for 3 months after their participation in the study ends.

- No experimental intravesical therapy within 6 weeks of study entry

Exclusion Criteria:

- 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) (see Appendix IV)

- 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 9.0 g/dL (Normal Range: Male: 13.5-17.5g/dL Female: 12.0-16.0 g/dL)

- Absolute neutrophil count: less than 1.5 x 10^9/L,

- Platelet count: less than 100 x 10^9/L (Normal Range: 150-400 x 10^9)

- Aspartate Aminotransferase Test (AST) / Serum Glutamic Oxaloacetic Transaminase (SGOT) and/or ( Alanine Aminotransferase Test (ALT)/ Serum Glutamic Pyruvic Transaminase (SGPT) >2.5 x ULN;

- Total bilirubin >1.0 x ULN,(Normal Range: Bilirubin, serum (adult) 0.1-1.0 mg/dL)

- Serum creatinine >1.5 x ULN. (Normal Range: 0.6-1.2mg/dL)

- 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.

- No IRB approved signed consent form
Location
Columbia University Medical Center- HIP
New York, New York, United States
Status: Recruiting
Contact: Jamie Pak - 212-305-6665 - jsp2187@columbia.edu
Start Date
December 2014
Completion Date
January 2016
Sponsors
Columbia University
Source
Columbia University
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page