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.
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.
|Overal Status||Start Date||Phase||Study Type|
|Recruiting||December 1, 2014||Phase 1||Interventional|
Primary Outcome 1 - Measure: The number of serious adverse events associated with therapy of intravesically administered Cabazitaxel, Gemcitabine, and Cisplatin.
Primary Outcome 1 - Time Frame: 6 weeks from baseline
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
- 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
- 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
- No experimental intravesical therapy within 6 weeks of study entry
- History of severe hypersensitivity reaction (≥grade 3) to docetaxel
- History of severe hypersensitivity reaction (≥grade 3) to polysorbate 80 containing
- 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
- 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
Minimum Age: 18 Years
Maximum Age: N/A
Healthy Volunteers: No
Name: Joel DeCastro, MD
Role: Principal Investigator
Affiliation: Columbia University
Name: Bridget Buckley-Matura, MPH
|Columbia University Medical Center- HIP
New York, New York 10032
Bridget Buckley-Matura, MPH