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

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

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.

Study Overview

• Status: Completed
• Conditions: Bladder Cancer
• Intervention / Treatment: Drug: Gemcitabine and Cisplatin (DD GC)

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Memorial Sloan Kettering at Basking Ridge
  • New York
    • Commack, New York, United States, 11725
      • Memorial Sloan Kettering Cancer Center @ Suffolk
    • Harrison, New York, United States, 10604
      • Memorial Sloan Kettering West Harrison
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10010
      • New York University
    • Rockville Centre, New York, United States, 11570
      • Memorial Sloan Kettering Cancer Center at Mercy Medical Center
    • Sleepy Hollow, New York, United States
      • Memoral Sloan Kettering Cancer Center@Phelps
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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
• If female of childbearing potential, pregnancy test is negative

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Gemcitabine and Cisplatin (DD GC); 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); 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Toxicity	Toxicity will be graded according to the National Cancer Institute Common Toxicity Criteria for Adverse Events version 4.0.	1 year
2 Year Recurrence Free Survival (RFS) Rate for Responders	Defined as the time from treatment initiation to disease progression, local-regional or metastatic recurrence, or death analyzed using the Kaplan Meier method.	2 years
2 Year Recurrence Free Survival (RFS) Rate for Nonresponders	Defined as the time from treatment initiation to disease progression, local-regional or metastatic recurrence, or death analyzed using the Kaplan Meier method.	2 years

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: New York University; University of North Carolina, Chapel Hill

Publications and helpful links

General Publications

• 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.

Helpful Links

• Memorial Sloan-Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): August 1, 2018
• Study Completion (Actual): August 1, 2018

Study Registration Dates

• First Submitted: April 27, 2012
• First Submitted That Met QC Criteria: April 27, 2012
• First Posted (Estimate): May 1, 2012

Study Record Updates

• Last Update Posted (Actual): October 2, 2019
• Last Update Submitted That Met QC Criteria: October 1, 2019
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: GM-CSF; radical cystectomy; CISPLATIN; GEMCITABINE; 12-071
• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Urinary Bladder Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine; Cisplatin
• Other Study ID Numbers: 12-071