Using crizotinib to treat lung cancer with specific gene mutations

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

This study is testing if the chemotherapy drug crizotinib can help people with advanced lung cancer that has certain gene mutations feel better and live longer.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University Health Network, Toronto (other)
• Drugs / interventions: Crizotinib, chemotherapy
• Locations: 1 site (Toronto, Ontario)
• Trial ID: NCT04084717 on ClinicalTrials.gov

What this trial studies

This phase 2 study evaluates the effectiveness of crizotinib, a chemotherapy drug, in patients with metastatic non-small cell lung cancer that has mutations in the ROS1 or MET genes. Participants will undergo a screening process to confirm eligibility, followed by a treatment period where they will receive crizotinib and have regular assessments for safety and efficacy. The study includes follow-up visits to monitor health status after treatment. The goal is to determine how well crizotinib works for these specific genetic alterations in lung cancer.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with stage IV non-squamous non-small cell lung cancer and documented ROS1 rearrangement or MET mutations.

Not a fit: Patients without ROS1 or MET gene mutations or those with contraindications to crizotinib therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a targeted therapy option for patients with ROS1 or MET mutated lung cancer, potentially improving outcomes.

How similar studies have performed: Previous studies have shown promising results for crizotinib in treating ROS1-positive lung cancer, indicating a potential for success in this approach.

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

Where this trial is running

Toronto, Ontario

• Princess Margaret Cancer Centre — Toronto, Ontario, Canada (RECRUITING)

Study contacts

• Principal investigator: Natasha Leighl, M.D. — Princess Margaret Cancer Centre
• Study coordinator: Natasha Leighl, M.D.

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