LCI-GU-URO-CRI-001: Crizotinib in Patients With c-MET or RON-Positive Metastatic Urothelial Cancer

NCT02612194 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: LCI-GU-URO-CRI-001
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single arm two-stage phase II study with crizotinib (Xalkori®) in the treatment of subjects with metastatic urothelial cancer of the bladder, upper (ureter or renal pelvis) or lower (urethra) urinary tracts. The purpose of this study is to see if this experimental drug has a potential benefit in subjects with stage 4 urothelial cancer. This study tests crizotinib used alone in subjects with urothelial cancer, previously treated with chemotherapy, and whose tumors have certain proteins. Proteins are complex natural substances essential to the structure and function of all living cells. These proteins, c-MET or RON, may trigger molecular pathways that are involved in the growth and spread of bladder or upper urinary tract cancer. Crizotinib is a drug taken by mouth that blocks these pathways. Early laboratory research suggests that crizotinib may benefit patients with urothelial and other cancers with these molecular pathways.

Conditions

Urinary Bladder Neoplasms; Ureteral Neoplasms; Urethral Neoplasms

Outcome Measures

Primary Outcomes (1)

• Overall Response

  Overall response will be determined as the best treatment response for each patient as a binary variable indicating whether or not the patient achieved a Complete Response (CR) or Partial Response (PR) as determined by RECIST v1.1 criteria. Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1):Complete Response (CR) is the disappearance of all lesions (target and non target); Partial Response (PR) is at least 30% decrease in the sum of the diameters of target lesions from baseline and no new lesions or unequivocal progression in non target lesions from baseline; Stable Disease (SD) is neither sufficient shrinkage in target lesions to qualify for PR (less than 30% decrease) nor sufficient increase in target lesions (versus smallest sum of diameters) to qualify for PD (less than 20% increase), with no new lesions or unequivocal progression in non target lesions from baseline. For the purposes of response determination, confirmatory scan for CR and PR is required.

  From enrollment to best response while on crizotinib; Subjects remained on treatment until disease progression or death or unacceptable toxicity (subjects were on treatment for an average of 6 weeks)

Secondary Outcomes (2)

• Overall Survival

  From date of treatment start to date of death, or censored as described above; assessed for approximately 2 years.

• Progression Free Survival

  From date of treatment start to date of progression or death, or censored as described above; assessed for approximately 2 years.

Study Arms (3)

Cohort 1

EXPERIMENTAL

c-MET high (\> 50%), RON null (0-9%)

Drug: Crizotinib

Cohort 2

EXPERIMENTAL

c-MET + (10-100%), RON + (10-100%)

Drug: Crizotinib

Cohort 3

EXPERIMENTAL

c-MET null (0-9%), RON + (10-100%)

Drug: Crizotinib

Interventions

Crizotinib DRUG

Crizotinib was administered orally at 250mg twice daily

Also known as: Xalkori

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

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

You may qualify if:

• Subjects must meet all of the following criteria:
• Histologically confirmed stage IV urothelial carcinoma of the bladder, upper urinary tract or urethra.
• Prior treatment for metastatic disease with at least one cisplatin or carboplatin-based multi-agent chemotherapeutic regimen. Prior immunotherapy with anti-PD-L1 or anti-PD1 agents is allowed.
• o Chemotherapy received peri-operatively for non-metastatic bladder cancer will be considered a prior regimen if less than 24 months have elapsed since treatment.
• Measurable disease per RECIST 1.1. See Section 10 for the evaluation of measurable disease.
• Tissue Pre-screen: Archived tissue must have been obtained within 60 months of subject signing tissue pre-screen consent. Biopsy accessible disease if adequate archival tissue does not exist for molecular characterization.
• Treatment: Available tumor specimen C-MET/RON expression results that meet the criteria for one of the three molecularly defined cohorts per Section 4.2
• Age ≥ 18 years
• ECOG performance status ≤ 2
• Adequate liver function: AST and ALT ≤ 2x upper limit of normal, bilirubin ≤ 1.5x upper limit of normal
• Adequate bone marrow function: Platelets ≥ 100,000 cells/mm3, hemoglobin \> 8.0 g/dL and ANC ≥ 1,500 cells/mm3
• Adequate renal function with a creatinine clearance (based on Cockgroft-Gault formula) ≥ 45 mL/min
• Ability to understand and the willingness to sign a written informed consent document
• Able to swallow oral medication

You may not qualify if:

• Subjects must not meet any of the following criteria
• Currently receiving any other investigational agents, a prior c-MET inhibitor, or crizotinib
• Pregnant or breast feeding, because crizotinib can cause fetal harm
• Uncontrolled and current illness including, but no limited to:
• Ongoing or active infection
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia, or
• Psychiatric illness/social situations that would limit compliance with study requirements
• Presence of any of the following within the previous 3 months of treatment consent:
• Myocardial infarction
• Severe/unstable angina
• Coronary/peripheral artery bypass graft
• Congestive heart failure, or
• Cerebrovascular accident including transient ischemia attack

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• Pfizer: collaborator

Study Sites (1)

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Ureteral Neoplasms; Urethral Neoplasms

Interventions

Crizotinib

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; Ureteral Diseases; Urethral Diseases

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Aminopyridines; Pyridines

Results Point of Contact

• Title: Chair of Biostatistics Department
• Organization: Levine Cancer Institute

james.symanowski@atriumhealth.org

9804422371

Study Officials

• Earle Burgess, MD

  Atrium Health (formerly Carolinas HealthCare System)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: November 19, 2015
• First Posted: November 23, 2015
• Study Start: September 27, 2016
• Primary Completion: September 17, 2019
• Study Completion: November 21, 2019
• Last Updated: November 3, 2022
• Results First Posted: June 9, 2021

Record last verified: 2021-05

Locations

US (1)