Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02202772
Recruitment Status : Active, not recruiting
First Posted : July 29, 2014
Last Update Posted : June 28, 2018
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
James M. McKiernan, Columbia University

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.

Condition or disease Intervention/treatment Phase
Urothelial Carcinoma of the Urinary Bladder Drug: Cabazitaxel Drug: Gemcitabine Drug: Cisplatin Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Trial for the Use of Intravesical Cabazitaxel, Gemcitabine, and Cisplatin (CGC) in the Treatment of BCG-Refractory Non-muscle Invasive Urothelial Carcinoma of the Bladder Cancer
Actual Study Start Date : December 1, 2014
Actual Primary Completion Date : June 1, 2018
Estimated Study Completion Date : December 1, 2020


Arm Intervention/treatment
Experimental: Gem and Low Cab
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
Intravesical instillation of the Cabazitaxel for 2 hours
Other Name: Jevtana

Drug: Gemcitabine
Intravesical instillation of Gemcitabine for 2 hours
Other Name: Gemzar

Experimental: Gem and High Cab
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
Intravesical instillation of the Cabazitaxel for 2 hours
Other Name: Jevtana

Drug: Gemcitabine
Intravesical instillation of Gemcitabine for 2 hours
Other Name: Gemzar

Experimental: Gem, High Cab, and Low Cis
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
Intravesical instillation of the Cabazitaxel for 2 hours
Other Name: Jevtana

Drug: Gemcitabine
Intravesical instillation of Gemcitabine for 2 hours
Other Name: Gemzar

Drug: Cisplatin
Intravesical installation of Cisplatin for 2hours
Other Name: Platinol, Platinol-AQ

Experimental: Gem, High Cab, Mod Cis
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
Intravesical instillation of the Cabazitaxel for 2 hours
Other Name: Jevtana

Drug: Gemcitabine
Intravesical instillation of Gemcitabine for 2 hours
Other Name: Gemzar

Drug: Cisplatin
Intravesical installation of Cisplatin for 2hours
Other Name: Platinol, Platinol-AQ

Experimental: Gem, High Cab, High Cis
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
Intravesical instillation of the Cabazitaxel for 2 hours
Other Name: Jevtana

Drug: Gemcitabine
Intravesical instillation of Gemcitabine for 2 hours
Other Name: Gemzar

Drug: Cisplatin
Intravesical installation of Cisplatin for 2hours
Other Name: Platinol, Platinol-AQ




Primary Outcome Measures :
  1. The number of serious adverse events associated with therapy of intravesically administered Cabazitaxel, Gemcitabine, and Cisplatin. [ Time Frame: 6 weeks from baseline ]
    The investigator is measuring safety by looking at the number of events that occur during the study


Secondary Outcome Measures :
  1. The number of complete responders after completion of six weeks of intravesically administered Cabazitaxel, Gemcitabine, and Cisplatin. [ Time Frame: 6 weeks from baseline ]
    The investigator is measuring efficacy by the number of complete responders to the treatment



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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.
  • 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., intrauterine device (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)
  • 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 >1.0 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.
  • No Institutional Review Board (IRB) approved signed consent form

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02202772


Locations
Layout table for location information
United States, New York
Columbia University Medical Center- HIP
New York, New York, United States, 10032
Sponsors and Collaborators
James M. McKiernan
Sanofi
Investigators
Layout table for investigator information
Principal Investigator: Guarionex DeCastro, MD Columbia University
  Study Documents (Full-Text)

Documents provided by James M. McKiernan, Columbia University:
Study Protocol  [PDF] December 21, 2017


Additional Information:
Layout table for additonal information
Responsible Party: James M. McKiernan, Chairman of Urology, Columbia University
ClinicalTrials.gov Identifier: NCT02202772    
Other Study ID Numbers: AAAM8506
First Posted: July 29, 2014    Key Record Dates
Last Update Posted: June 28, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by James M. McKiernan, Columbia University:
Urothelial
Cisplatin
Gemcitabine
Cabazitaxel
Bladder
Carcinoma
Bacillus Calmette-Guerin
Intravesical
Recurrent
Non-muscle
Invasive
Cancer
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma
Carcinoma, Transitional Cell
Urinary Bladder Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
Gemcitabine
Cisplatin
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs