Neoadjuvant Dose Dense Gemcitabine and Cisplatin (DD GC) In Patients With Muscle-Invasive Bladder Cancer

NCT01589094 | Completed Phase 2 Results

• 1 other identifier: 12-071
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 8

Brief Summary

The purpose of this study is to find out if standard chemotherapy (gemcitabine and cisplatin) given on a dose-dense treatment schedule (with less time between treatments) can help shrink the tumor better than standard chemotherapy given on a standard treatment schedule before the patient undergoes surgery for bladder cancer.

Conditions

Bladder Cancer

Keywords

CISPLATIN; GEMCITABINE; GM-CSF; radical cystectomy; 12-071

Outcome Measures

Primary Outcomes (1)

• Pathologic Response Rate

  Defined as the absence of muscle invasive carcinoma (\<pT2 disease) and the absence of lymph node metastases (N0) on the final cystectomy specimen. Pathologists will assess surgical specimens systematically using criteria agreed upon for all conventional neoadjuvant treatment based on the AJCC TNM staging system.

  1 year

Secondary Outcomes (3)

• Number of Participants With Toxicity

  1 year

• 2 Year Recurrence Free Survival (RFS) Rate for Responders

  2 years

• 2 Year Recurrence Free Survival (RFS) Rate for Nonresponders

  2 years

Study Arms (1)

Gemcitabine and Cisplatin (DD GC)

EXPERIMENTAL

This is a Multicenter Phase II study of dose-dense (DD) gemcitabine and cisplatin (GC) neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer (MIBC) who are candidates for radical cystectomy.

Drug: Gemcitabine and Cisplatin (DD GC)

Interventions

Gemcitabine and Cisplatin (DD GC) DRUG

Patients will receive six cycles of GC administered every 14 days. Gemcitabine 2,500 mg/m2 will be administered intravenously on day 1 and cisplatin 35 mg/m2 will be administered intravenously on days 1 and 2 of a 14 days cycle (with Peg GCSF). A total of six cycles of therapy will be administered followed by radical cystectomy with bilateral pelvic lymph node dissection (PLND)

Gemcitabine and Cisplatin (DD GC)

Eligibility Criteria

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

You may qualify if:

• Muscle invasive urothelial carcinoma of the bladder histologically confirmed at MSKCC or participating site ((Urothelial carcinoma invading into the prostatic stroma with no histologic muscle invasion is allowed, provided the extent of disease is confirmed via imaging and/or EUA.)
• Clinical stage T2-T4a N0/X M0 disease
• Medically appropriate candidate for radical cystectomy, as per MSKCC or participating site
• Karnofsky Performance Status ≥ 70%
• Age ≥ 18 years of age
• Required Initial Laboratory Values:
• Absolute Neutrophil Count ≥ 1000 cells/mm3
• Platelets ≥ 100,000 cells/mm3
• Hemoglobin ≥ 9.0g/dL
• Bilirubin ≤ 1.5 the upper limit of normal (ULN) for the institution
• Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN for the institution
• Alkaline phosphatase ≤ 2.5 x ULN for the institution
• Serum creatinine ≤ 1.5 mg/dL
• Estimated glomerular filtration rate ≥ 60 ml/min/1.73m2 using the CKD-EPI equation: eGFR = 141 x min(Scr/k, 1)a x max(Scr/k, 1)-1.209 x 0.993Age
• x 1.018 \[if female\] x 1.159 \[if black\] Scr is serum creatinine, k is 0.7 for females and 0.9 for males, a is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/k or 1, and max indicates the maximum of Scr/k or 1

You may not qualify if:

• Prior systemic chemotherapy (prior intravesical therapy is allowed)
• Prior radiation therapy to the bladder
• Evidence of NYHA functional class III or IV heart disease
• Serious intercurrent medical or psychiatric illness, including serious active infection
• Preexisting sensory grade ≥ 2 neuropathy
• Preexisting grade ≥ 2 hearing loss
• Major surgery or radiation therapy \< 4 weeks of starting study treatment
• Concomitant use of any other investigational drugs
• Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attack
• Ongoing cardiac dysrhythmias of NCI CTCAE Version 4.0 grade ≥ 2
• Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness or other active infection
• Concurrent treatment on another clinical trial; supportive care trials or non-treatment trials, e.g. QOL, are allowed
• Pregnancy or breast-feeding. Patients must be surgically sterile, postmenopausal, or must agree to use effective contraception during the period of therapy. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate. Male patients must be surgically sterile or agree to use effective contraception.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• University of North Carolina, Chapel Hill: collaborator
• New York University: collaborator

Study Sites (8)

Memorial Sloan Kettering at Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Cancer Center @ Suffolk

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering West Harrison

Harrison, New York, 10604, United States

Location

New York University

New York, New York, 10010, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Cancer Center at Mercy Medical Center

Rockville Centre, New York, 11570, United States

Location

Memoral Sloan Kettering Cancer Center@Phelps

Sleepy Hollow, New York, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27514, United States

Location

Related Publications (1)

• Iyer G, Balar AV, Milowsky MI, Bochner BH, Dalbagni G, Donat SM, Herr HW, Huang WC, Taneja SS, Woods M, Ostrovnaya I, Al-Ahmadie H, Arcila ME, Riches JC, Meier A, Bourque C, Shady M, Won H, Rose TL, Kim WY, Kania BE, Boyd ME, Cipolla CK, Regazzi AM, Delbeau D, McCoy AS, Vargas HA, Berger MF, Solit DB, Rosenberg JE, Bajorin DF. Multicenter Prospective Phase II Trial of Neoadjuvant Dose-Dense Gemcitabine Plus Cisplatin in Patients With Muscle-Invasive Bladder Cancer. J Clin Oncol. 2018 Jul 1;36(19):1949-1956. doi: 10.1200/JCO.2017.75.0158. Epub 2018 May 9.

  PMID: 29742009 DERIVED

Related Links

• Memorial Sloan-Kettering Cancer Center

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Gemcitabine; Cisplatin

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dean Bajorin, MD
• Organization: Memorial Sloan Kettering Cancer Center

bajorind@mskcc.org

646-888-4700

Study Officials

• Dean Bajorin, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2012
• First Posted: May 1, 2012
• Study Start: April 1, 2012
• Primary Completion: August 1, 2018
• Study Completion: August 1, 2018
• Last Updated: October 2, 2019
• Results First Posted: October 2, 2019

Record last verified: 2018-08

Locations

US (8)