Crizotinib for Cancer with ROS1 Genetic Changes

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inhibitors, ROS1 inhibitors

Disqualifiers: NSCLC, Interstitial lung disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: Up to 3 years

4 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II MATCH treatment trial identifies the effects of crizotinib in patients whose cancer has a genetic change called ROS1 translocation. Crizotinib may block a protein called ROS1, which may be needed for cancer cell growth. Researchers hope to learn if crizotinib will shrink this type of cancer or stop its growth.

Will I have to stop taking my current medications?

The trial requires that you do not use drugs or foods that are known potent CYP3A4 inhibitors or inducers, as these can affect how crizotinib works. If you are taking any of these, you may need to stop them before joining the trial.

What data supports the effectiveness of the drug Crizotinib for cancer with ROS1 genetic changes?

Crizotinib has shown strong antitumor activity in patients with ROS1-positive advanced non-small-cell lung cancer (NSCLC), leading to increased progression-free survival and improved quality of life. It is considered a safe and effective treatment for patients with this specific genetic change in lung cancer. ^{1 2 3 4 5}

Is Crizotinib safe for humans?

Crizotinib is generally well tolerated in humans, with common side effects including vision problems, nausea, diarrhea, and fatigue. Some patients may experience more serious effects like changes in heart rhythm and liver function, so monitoring is important. ^{6 7 8 9 10}

How is the drug Crizotinib unique for treating cancer with ROS1 genetic changes?

Crizotinib is unique because it is an oral drug that specifically targets ROS1, a gene involved in certain cancers, and it has shown significant effectiveness in treating non-small-cell lung cancer with ROS1 rearrangements. Unlike some other treatments, it directly inhibits the activity of the ROS1 protein, which is a key driver in these cancers. ^{2 3 4 11 12}

Research Team

Aaron S Mansfield

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

This trial is for cancer patients with a specific genetic change called ROS1 translocation, excluding those with non-small cell lung cancer (NSCLC) or a history of lung disease. Participants must have normal heart rhythms and not be allergic to crizotinib or similar compounds. They can't use certain drugs that affect crizotinib's metabolism and shouldn't have used any ROS1 inhibitors before.

Inclusion Criteria

Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol

My recent ECG showed no significant heart issues.

My cancer has a specific genetic change in the ROS1 gene.

Exclusion Criteria

Patients must not have known hypersensitivity to crizotinib or compounds of similar chemical or biologic composition

I am not using any strong medications or foods that affect drug metabolism.

I have never been treated with ROS1 inhibitors.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive crizotinib orally twice daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Up to 3 years

Every 2 cycles for the first 26 cycles, then every 3 cycles thereafter

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-ups every 3 months if less than 2 years from study entry, and then every 6 months for year 3.

Up to 3 years

Treatment Details

Interventions

• Crizotinib

Trial Overview The study tests Crizotinib, which may inhibit the growth of cancers by blocking the protein ROS1. It's for patients whose cancers are identified to have this targetable genetic alteration. The goal is to see if Crizotinib can shrink these cancers or halt their progression.

Participant Groups

Group I: Treatment (crizotinib) Experimental Treatment 1 Intervention

Patients receive crizotinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Crizotinib is already approved in United States, European Union, Japan, Canada for the following indications:

Approved in United States as Xalkori for:

• Non-small cell lung cancer (NSCLC) with ALK rearrangements

Approved in European Union as Xalkori for:

• Non-small cell lung cancer (NSCLC) with ALK rearrangements

Approved in Japan as Xalkori for:

• Non-small cell lung cancer (NSCLC) with ALK rearrangements

Approved in Canada as Xalkori for:

• Non-small cell lung cancer (NSCLC) with ALK rearrangements

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

ROS1 fusion events occur in 1%-2% of non-small-cell lung cancer (NSCLC) patients and are associated with specific patient demographics, including younger individuals, women, and non-smokers, indicating a distinct molecular subtype of NSCLC.

Crizotinib is the only approved treatment for ROS1-rearranged NSCLC, showing significant benefits in progression-free survival and quality of life, and is recommended as the standard first-line therapy for patients with this genetic alteration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Crizotinib inhibition of ROS1-positive tumours in advanced non-small-cell lung cancer: a Canadian perspective. Bebb, DG., Agulnik, J., Albadine, R., et al.[2023]

In a study of 35 Chinese patients with advanced non-small-cell lung cancer (NSCLC) harboring ROS1 rearrangements, crizotinib demonstrated a high objective response rate of 71.4% and a disease control rate of 94.3%, indicating its efficacy in real-world clinical practice.

The median progression-free survival was 11 months and median overall survival was 41 months, with crizotinib being well tolerated despite some common adverse effects like elevated transaminases and vision disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Crizotinib in Chinese Patients with ROS1-Rearranged Advanced Non‒Small-Cell Lung Cancer in Routine Clinical Practice. Liu, C., Yu, H., Chang, J., et al.[2022]

In a phase II trial involving 127 East Asian patients with ROS1-positive advanced non-small-cell lung cancer (NSCLC), crizotinib showed a high objective response rate of 71.7%, indicating significant antitumor activity.

The treatment was well tolerated, with no new safety concerns reported, and patients experienced durable responses, with a median duration of response of 19.7 months and a median progression-free survival of 15.9 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Study of Crizotinib in East Asian Patients With ROS1-Positive Advanced Non-Small-Cell Lung Cancer. Wu, YL., Yang, JC., Kim, DW., et al.[2022]

Crizotinib is an effective treatment for adults with ALK-rearranged non-small-cell lung cancer, but managing its common side effects is essential for maintaining treatment continuity and achieving optimal survival rates.

While some side effects like visual disturbances and bradycardia are generally mild, serious cardiac and liver-related adverse events require careful monitoring, particularly for QT interval prolongation and liver function, to ensure patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ALK-rearranged non-small cell lung cancers: how best to optimize the safety of crizotinib in clinical practice? Girard, N., Audigier-Valette, C., Cortot, AB., et al.[2018]

Crizotinib is an effective oral tyrosine kinase inhibitor specifically targeting ALK, which is found in about 5% of non-small-cell lung cancers (NSCLCs), and has been approved for treating advanced ALK-rearranged NSCLC.

Clinical trials have demonstrated that crizotinib is superior to standard chemotherapy for patients with ALK-positive NSCLC, highlighting its efficacy in this specific cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Crizotinib in the treatment of non--small-cell lung cancer. Rothschild, SI., Gautschi, O.[2021]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Crizotinib inhibition of ROS1-positive tumours in advanced non-small-cell lung cancer: a Canadian perspective. [2023]

2. France pubmed.ncbi.nlm.nih.gov

Crizotinib in Chinese Patients with ROS1-Rearranged Advanced Non‒Small-Cell Lung Cancer in Routine Clinical Practice. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Crizotinib in ROS1-rearranged non-small-cell lung cancer. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

A Novel Crizotinib-Resistant Solvent-Front Mutation Responsive to Cabozantinib Therapy in a Patient with ROS1-Rearranged Lung Cancer. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Clinical and molecular factors that impact the efficacy of first-line crizotinib in ROS1-rearranged non-small-cell lung cancer: a large multicenter retrospective study. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Phase II Study of Crizotinib in East Asian Patients With ROS1-Positive Advanced Non-Small-Cell Lung Cancer. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Benefit-Risk Summary of Crizotinib for the Treatment of Patients With ROS1 Alteration-Positive, Metastatic Non-Small Cell Lung Cancer. [2022]

8. England pubmed.ncbi.nlm.nih.gov

ALK-rearranged non-small cell lung cancers: how best to optimize the safety of crizotinib in clinical practice? [2018]

9. United States pubmed.ncbi.nlm.nih.gov

Crizotinib in the treatment of non--small-cell lung cancer. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Atrial fibrillation was changed into sinus bradycardia in a ROS1-positive advanced lung adenocarcinoma patient who achieved durable response to Crizotinib: A case report and literature review. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Cabozantinib overcomes crizotinib resistance in ROS1 fusion-positive cancer. [2022]

12. England pubmed.ncbi.nlm.nih.gov

ROS1 [corrected]. [2018]