Genetic Determinants of Response to Neoadjuvant Cisplatin-based Chemotherapy in Urothelial Cancer

Identification of Genetic Determinants of Response to Neoadjuvant Cisplatin-based Chemotherapy in Urothelial Cancer

This is observational clinical trial to study adult urothelial cancer patients treated with cisplatin-based neoadjuvant chemotherapy.

Hypothesis: Identification of genetic and molecular "cisplatin susceptibility" biomarkers will allow identification of urothelial cancer patients most likely to benefit from cisplatin-based neoadjuvant chemotherapy.

Study Overview

• Status: Completed
• Conditions: Urothelial Cancer

Detailed Description

In this trial patients will submit germline (blood) and tumor tissue samples as part of two existing sample collection protocols for analysis of genetic and molecular markers governing response to chemotherapy. Pathologic review of tissue samples after neoadjuvant therapy will allow determination of the complete response rate (pT0 rate) and this will be compared between patients with "susceptible" and "resistant" genetic/molecular cisplatin susceptibility variants.

Primary Endpoint: Analysis of whether a small set of previously-identified germline "cisplatin susceptibility" polymorphisms associate with achievement of a complete pathologic response to neoadjuvant cisplatin-based chemotherapy in urothelial cancer patients.

Secondary Endpoints: To perform companion genetic or molecular analyses of other previously-identified gene, SNP, or microRNA "cisplatin susceptibility" candidates in these patients, using tumor and/or germline tissue.

Exploratory Endpoints: To perform unbiased, hypothesis-generating SNP, gene, or microRNA array studies to identify novel germline or tumor determinants which may predict response to cisplatin-based chemotherapy.

• Study Type: Observational
• Enrollment (Actual): 79

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 89 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Eligible patients who are about to begin neoadjuvant cisplatin-based chemotherapy for urothelial cancer and who have consented to IRB approved protocols #15550B and/or TRIDOM (IRB #14104B).

Description

Inclusion Criteria:

• Patients with clinical T2 through T4 urothelial carcinoma of the bladder or upper tract.
• Patients must be deemed appropriate by the treating physician to require cisplatin-based neoadjuvant chemotherapy for urothelial cancer. Consideration of regional nodal status as part of the decision for appropriateness for neoadjuvant chemotherapy will be left to the treating physician.
• Patients must be scheduled to proceed to definitive urothelial cancer surgery, including either cystectomy or nephrectomy/ureterectomy, after chemotherapy.
• Age >18 years.

Exclusion Criteria:

• Patients receiving cisplatin-based chemotherapy for urothelial cancer in the adjuvant setting or for metastatic disease.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genetic Determinants of pT0 Status	To perform genetic analysis of germline samples from these patients to determine whether a set of "cisplatin susceptibility" polymorphisms predict complete pathologic response to cisplatin-based chemotherapy.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Molecular Determinants of pT0 Status	To perform companion genetic or molecular analyses of other previously-identified gene, SNP, or microRNA "cisplatin susceptibility" candidates in these patients, using tumor or germline tissue.	3 years

Collaborators and Investigators

• Sponsor: University of Chicago
• Investigators: Principal Investigator: Peter H O'Donnell, MD, University of Chicago

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2009
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): October 16, 2017

Study Registration Dates

• First Submitted: September 13, 2010
• First Submitted That Met QC Criteria: September 20, 2010
• First Posted (Estimate): September 21, 2010

Study Record Updates

• Last Update Posted (Actual): May 4, 2018
• Last Update Submitted That Met QC Criteria: May 1, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Urothelial, cancer, cisplatin, neoadjuvant, chemotherapy, germline
• Other Study ID Numbers: 09-288-B

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No