LCI-GU-URO-CRI-001: Crizotinib in Patients With c-MET or RON-Positive Metastatic Urothelial Cancer
NCT02612194
ABOUT THIS STUDY
FOR MORE INFORMATION
Contact a representative by phone, email, or visiting the study website. Please see the references below:
Pfizer Clinical Trials Contact Center
1-800-718-1021
Subjects must meet all of the following criteria:
1. Histologically confirmed stage IV urothelial carcinoma of the bladder, upper urinary tract or urethra.
2. 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.
3. Measurable disease per RECIST 1.1. See Section 10 for the evaluation of measurable disease.
4. 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
5. Age ≥ 18 years
6. ECOG performance status ≤ 2
7. Adequate liver function: AST and ALT ≤ 2x upper limit of normal, bilirubin ≤ 1.5x upper limit of normal
8. Adequate bone marrow function: Platelets ≥ 100,000 cells/mm3, hemoglobin > 8.0 g/dL and ANC ≥ 1,500 cells/mm3
9. Adequate renal function with a creatinine clearance (based on Cockgroft-Gault formula) ≥ 45 mL/min
10. Ability to understand and the willingness to sign a written informed consent document
11. Able to swallow oral medication
Subjects must not meet any of the following criteria
1. Currently receiving any other investigational agents, a prior c-MET inhibitor, or
crizotinib
2. Pregnant or breast feeding, because crizotinib can cause fetal harm
3. 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
4. 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
5. History of active malignancy other than urothelial carcinoma within the prior 12
months of the date of treatment consent (except non-melanoma skin cancer or localized,
treated prostate cancer)
6. Prolonged QT interval (QTc > 480 msec), symptomatic bradycardia, ongoing cardiac
dysrhythmias of CTCAE version 4.0 grade 2 ≥ or uncontrolled atrial fibrillation of any
grade
7. Pulmonary disorder requiring supplemental oxygen or history of pulmonary fibrosis.
Sleep apnea considered to be a sleep disorder (and not a pulmonary disorder) by the
investigator will be allowed.
8. Subjects receiving any medications or substances that are strong inhibitors or
inducers of CYP3A are ineligible. Because the lists of these agents are constantly
changing, it is important to regularly consult a frequently updated list such as
http://medicine.iupui.edu/clinpharm/ddis/table/aspx; medical reference texts such as
the Physicians' Desk Reference may also provide this information. As part of the
enrollment/informed consent procedures, the subject will be counseled on the risk of
interactions with other agents, and what to do if new medications need to be
prescribed or if the subject is considering a new over-the-counter medicine or herbal
product.
- Medical condition requiring the use of strong CPY3A inhibitors, including but not
limited to atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole,
nefazodone, nelfinavir, ritonavir, saquinavir, suboxone, telithromycin,
troleandomycin, and voriconazole.
- Use of grapefruit or grapefruit juice, which are considered strong CYP3A
inhibitors.
- Medical condition requiring the use of strong CYP3A inducers, including but not
limited to carbamazepine, efavirenz, modafinil, nevirapine, oxcarbazepine,
phenobarbital, phenytoin, pioglitazone, rifabutin, rifampin, St. John's Wort, and
troglitazone.
9. Receiving any medications that are CYP3A substrates with a narrow therapeutic range
(alfentanil, cyclosporine, dihydroergotamine, fentanyl, pimozide, quinidine, sirolimus
and tacrolimus)
10. Subjects may be screened for study participation though may not begin study treatment:
- Within 4 weeks of major surgery
- Within 2 weeks of prior systemic therapy
- Within 2 weeks of prior non-palliative radiotherapy
- Within 48 hours of completion of palliative radiotherapy (≤ 10 fractions)
- Until recovery of adverse events due to prior therapies to ≤ 1 (except alopecia)
11. Presence of untreated brain metastases or ≤ 6 months from prior treatment (from the
time of enrollment), active neurologic symptoms or the use of prohibited medications
in subjects with a history of brain metastases
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Descriptive Information | |||||||
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Brief Title ICMJE | LCI-GU-URO-CRI-001: Crizotinib in Patients With c-MET or RON-Positive Metastatic Urothelial Cancer | ||||||
Official Title ICMJE | LCI-GU-URO-CRI-001: A Phase II Study of Crizotinib in Patients With c-MET or RON-Positive Metastatic Urothelial Cancer | ||||||
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. | ||||||
Detailed Description | This is a single arm two-stage phase II study designed to evaluate the objective response rate in subjects with metastatic urothelial cancer demonstrating c-MET or RON overexpression who have received prior therapy with a cisplatin or carboplatin containing regimen. Subjects will be recruited at Levine Cancer Institute (LCI) and other participating sites. Immunohistochemistry will be utilized to define tumor sample c-MET and RON protein expression patterns for assignment into molecular cohorts as described in section 12.1. In the first stage of this study, subjects will be enrolled in parallel to three molecularly defined cohorts as follows:
All enrolled subjects will continue with study treatment until criteria for treatment discontinuation has been met. If Stage 1 response criteria are met in a cohort, the cohort may be considered for expansion, and additional subjects (16 in Cohort 1 or 25 in Cohorts 2 or 3) may then be enrolled into that cohort in Stage 2. An expansion cohort will be defined by the Sponsor- Investigator following review of all available trial data which will be conducted after the first Stage 1 cohort has completed accrual and at least every six months thereafter until all Stage 1 cohorts have completed accrual. If more than one cohort meets Stage 1 response criteria (2 responses out of 14 subjects for Cohort 1 or 1 response out of 7 subjects for each of Cohorts 2 and 3), then the cohort showing the highest response rate will be given highest consideration for expansion. | ||||||
Study Type ICMJE | Interventional | ||||||
Study Phase ICMJE | Phase 2 | ||||||
Study Design ICMJE | Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment | ||||||
Condition ICMJE |
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Intervention ICMJE | Drug: Crizotinib
All arms will receive crizotinib. Other Name: Xalkori | ||||||
Study Arms ICMJE |
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Publications * | Not Provided | ||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. | |||||||
Recruitment Information | |||||||
Recruitment Status ICMJE | Terminated | ||||||
Estimated Enrollment ICMJE | 46 | ||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||
Actual Study Completion Date ICMJE | November 21, 2019 | ||||||
Actual Primary Completion Date | September 17, 2019 (Final data collection date for primary outcome measure) | ||||||
Eligibility Criteria ICMJE | Inclusion Criteria Subjects must meet all of the following criteria:
Exclusion Criteria Subjects must not meet any of the following criteria
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||||
Accepts Healthy Volunteers ICMJE | No | ||||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||||
Listed Location Countries ICMJE | United States | ||||||
Removed Location Countries | |||||||
Administrative Information | |||||||
NCT Number ICMJE | NCT02612194 | ||||||
Other Study ID Numbers ICMJE | LCI-GU-URO-CRI-001 | ||||||
Has Data Monitoring Committee | Yes | ||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE | Not Provided | ||||||
Responsible Party | Earle Burgess, MD, Atrium Health | ||||||
Study Sponsor ICMJE | Earle Burgess, MD | ||||||
Collaborators ICMJE | Pfizer | ||||||
Investigators ICMJE |
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PRS Account | Atrium Health | ||||||
Verification Date | August 2020 | ||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |