Study of Crizotinib for ROS1 and MET Activated Lung Cancer

Stage IV Non-small Cell Lung Cancer Clinical Trial

Official title:

Phase II Study of Crizotinib for ROS1 and MET Activated Lung Cancer (CROME)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04084717
• Other study ID #: 18-5607
• Secondary ID: CROME / WI235747
• Status: Recruiting
• Phase: Phase 2
• Start date: December 3, 2019
• Est. completion date: June 2025

Study information

• Verified date: June 2023
• Source: University Health Network, Toronto
• Contact: Natasha Leighl, M.D.
• Phone: 416-946-4645
• Email: natasha.leighl[@]uhn.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a phase 2 study of a drug called crizotinib in people with metastatic (the cancer has spread to other parts of the body) non-small cell lung cancer with a mutation (change) in genes called ROS1 or MET. The purpose of this study is to look at how effective crizotinib is at treating ROS1 or MET mutated non-small cell lung cancer.

Crizotinib, also called XALKORI, is a chemotherapy drug that is currently approved for the treatment of ALK- or ROS1- positive advanced non-small cell lung cancer.

Description:

The study consists of a screening period, study drug period, end of study drug visit and follow-up period.

During the screening period, participants will be asked to have tests and procedures done to make sure that they are eligible to continue in the study. Screening may take several visits. Participants found to be eligible to continue in the study, will then enter the study drug period where they will take the study drug and have tests and procedures done about once a week for safety and for research purposes.

Participants who stop the study drug completely for any reason, will be asked to return to the clinic for an end of study drug visit about 28 days after their last dose of study drug to have tests and procedures done for safety and for research purposes. Participants that are experiencing any side effects during this time, will be closely followed by their study Doctor until the side effects have resolved or stabilized.

Participants who discontinue study drug for any reason other than disease progression, will be asked to have radiological imaging every 8 weeks to follow up on the status of their disease, until disease progression or the start a new treatment for their cancer.

After their final visit, the study nurse will call participants approximately every 3 months to check on the status of their health.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: June 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of stage IV or incurable non-squamous non-small cell lung cancer with a documented ROS1 rearrangement (cohort 1) or MET-activating mutation (exon 14) (cohort 2) or MET-amplification (cohort 3) tested in either plasma or tissue, as applicable

• 18 years of age or older.

• Measurable disease as per RECIST v1.1.

• Adequate hematologic and organ function within 7 days of the proposed start date of treatment and adequate cardiac function within 28 days of the proposed start date of treatment

• Life expectancy >12 weeks.

• Have the ability to understand and the willingness to sign a written informed consent document

• Eastern Cooperative Oncology Group (ECOG) performance status =2

• No contraindication to Crizotinib therapy

• Able to swallow and retain oral medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels.

• No pregnant

• Agree to use methods (as agreed upon by the study doctor and participant) before the study and for at least 120 days after the last dose of study drug to prevent pregnancy

Exclusion Criteria:

• Symptomatic untreated brain metastases.

• Had chemotherapy (including investigational cytotoxic chemotherapy), biologic agents (e.g. targeted therapy or antibodies) within 4 weeks or radiotherapy within 2 weeks prior to the proposed first dose of study treatment.

• Adverse events attributed to prior anti-cancer therapy > Grade 1 if clinically relevant.

• Receiving medications or substances known to be strong inhibitors or inducers of CYP3A4.

• Any known intolerance to agents structurally similar to crizotinib.

• Congenital long QT syndrome or persistent corrected QT interval by Fredericia formula (QTcF) = 500 msec.

• Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures, e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, social/ psychological issues

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• MET Activating Mutation
• MET Amplification
• Non-squamous Non-small-cell Lung Cancer
• ROS1 Gene Rearrangement
• Stage IV Non-small Cell Lung Cancer

Intervention

Drug:
• Crizotinib
Crizotinib is an orally administered, chemotherapy drug that works by blocking ALK, MET and ROS1 receptor tyrosine kinases from working. Participants will receive crizotinib, orally (by mouth), at a dose of 250 mg, twice per day, every day of each 28 day cycle.

Locations

Country	Name	City	State
Canada	Princess Margaret Cancer Centre	Toronto	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
University Health Network, Toronto	Pfizer

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response Rate	Via RECIST 1.1	5 years
Primary	Progression-free survival	Via RECIST 1.1	5 years
Primary	Average Time-to-treatment Failure	Time from randomization to treatment discontinuation for any reason	5 years
Primary	Edmonton Symptom Assessment Scale (ESAS) Score	Patient related symptom improvement evaluated by ESAS	5 years
Primary	EQ5D-5L Questionnaire Score	Patient preference/health related utility evaluated by EQ5D-5L Questionnaire	5 years
Primary	Overall survival	Number of days from the date of randomization to the date of death	2 years