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Study of Crizotinib for ROS1 and MET Activated Lung Cancer

Primary Purpose

Non-squamous Non-small-cell Lung Cancer, Stage IV Non-small Cell Lung Cancer, ROS1 Gene Rearrangement

Status

Recruiting

Phase

Phase 2

Locations

Canada

Study Type

Interventional

Intervention

Crizotinib

About this trial

This is an interventional treatment trial for Non-squamous Non-small-cell Lung Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Princess Margaret Cancer CentreRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

ROS1 Rearrangement

MET-activating Mutation (exon 14)

MET-amplification

Arm Description

Patients with stage IV or incurable non-squamous non-small cell lung cancer with a documented ROS1 rearrangement will be assigned to this arm.

Patients with stage IV or incurable non-squamous non-small cell lung cancer with a documented MET-activating mutation (exon 14) will be assigned to this arm.

Patients with stage IV or incurable non-squamous non-small cell lung cancer with a documented MET-amplification will be assigned to this arm.

Outcomes

Primary Outcome Measures

Response Rate

Via RECIST 1.1

Progression-free survival

Via RECIST 1.1

Average Time-to-treatment Failure

Time from randomization to treatment discontinuation for any reason

Edmonton Symptom Assessment Scale (ESAS) Score

Patient related symptom improvement evaluated by ESAS

EQ5D-5L Questionnaire Score

Patient preference/health related utility evaluated by EQ5D-5L Questionnaire

Overall survival

Number of days from the date of randomization to the date of death

Secondary Outcome Measures

Full Information

NCT ID

NCT04084717

First Posted

September 8, 2019

Last Updated

June 15, 2023

Sponsor

University Health Network, Toronto

Collaborators

Pfizer

1. Study Identification

Unique Protocol Identification Number

NCT04084717

Brief Title

Study of Crizotinib for ROS1 and MET Activated Lung Cancer

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Recruiting

Study Start Date

December 3, 2019 (Actual)

Primary Completion Date

December 2024 (Anticipated)

Study Completion Date

June 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Health Network, Toronto

Collaborators

Pfizer

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

Participants will be assigned to one of the following: Cohort 1 - ROS1 rearrangement Cohort 2 - MET-activating mutation (exon 14) Cohort 3 - MET-amplification

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

ROS1 Rearrangement

Arm Type

Experimental

Arm Description

Patients with stage IV or incurable non-squamous non-small cell lung cancer with a documented ROS1 rearrangement will be assigned to this arm.

Arm Title

MET-activating Mutation (exon 14)

Arm Type

Experimental

Arm Description

Patients with stage IV or incurable non-squamous non-small cell lung cancer with a documented MET-activating mutation (exon 14) will be assigned to this arm.

Arm Title

MET-amplification

Arm Type

Experimental

Arm Description

Patients with stage IV or incurable non-squamous non-small cell lung cancer with a documented MET-amplification will be assigned to this arm.

Intervention Type

Drug

Intervention Name(s)

Crizotinib

Other Intervention Name(s)

XALKORI

Intervention Description

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.

Primary Outcome Measure Information:

Title

Response Rate

Description

Via RECIST 1.1

Time Frame

5 years

Title

Progression-free survival

Description

Via RECIST 1.1

Time Frame

5 years

Title

Average Time-to-treatment Failure

Description

Time from randomization to treatment discontinuation for any reason

Time Frame

5 years

Title

Edmonton Symptom Assessment Scale (ESAS) Score

Description

Patient related symptom improvement evaluated by ESAS

Time Frame

5 years

Title

EQ5D-5L Questionnaire Score

Description

Patient preference/health related utility evaluated by EQ5D-5L Questionnaire

Time Frame

5 years

Title

Overall survival

Description

Number of days from the date of randomization to the date of death

Time Frame

2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Natasha Leighl, M.D.

Phone

416-946-4645

natasha.leighl@uhn.ca

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Natasha Leighl, M.D.

Organizational Affiliation

Princess Margaret Cancer Centre

Official's Role

Principal Investigator

Facility Information:

Facility Name

Princess Margaret Cancer Centre

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5G 1Z5

Country

Canada

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Natasha Leighl

Phone

416-946-4645

natasha.leighl@uhn.ca

First Name & Middle Initial & Last Name & Degree

Natasha Leighil, M.D.

12. IPD Sharing Statement

Learn more about this trial

Study of Crizotinib for ROS1 and MET Activated Lung Cancer

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