Crizotinib for Cancer

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Heart disease, Lung disease, Recent surgery, 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: 5

Duration: Up to 3 years

35 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II MATCH treatment trial tests how well crizotinib works to treat patients with cancers with MET exon 14 deletion genetic changes. Crizotinib is in a group of medications called tyrosine kinase inhibitors. It works by blocking enzymes that cancer cells need to grow and spread. It may also prevent the growth of new blood vessels that tumors need to grow.

Do I have to stop taking my current medications for the trial?

The trial requires that you do not use drugs or foods that are strong CYP3A4 inhibitors or inducers, and you must not need to use CYP3A substrates with narrow therapeutic indices. If you are taking any of these, you may need to stop or adjust them.

What data supports the effectiveness of the drug Crizotinib (Xalkori) for cancer treatment?

Crizotinib has been shown to be effective in treating advanced non-small cell lung cancer (NSCLC) that is positive for a specific gene change called ALK. Studies have found that patients with this type of cancer who took Crizotinib had significant improvements in how long they lived without the cancer getting worse and in their overall quality of life compared to those who received standard chemotherapy. ^{1 2 3 4 5}

Is crizotinib generally safe for humans?

Crizotinib has been generally well tolerated in clinical studies, with most side effects being mild to moderate, such as vision disorders, nausea, and diarrhea. Serious side effects are rare, but monitoring for liver function and heart-related issues is recommended. ^{1 2 3 6 7}

How is the drug Crizotinib unique in treating cancer?

Crizotinib is unique because it is an oral medication that specifically targets and inhibits certain proteins (ALK, MET, and ROS1) involved in the growth of cancer cells, particularly in ALK-positive non-small cell lung cancer, leading to improved outcomes compared to standard chemotherapy. ^{1 2 3 4 8}

Research Team

David S Hong

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

This trial is for patients with various types of cancer, such as lymphoma and solid tumors, that have a specific genetic change called MET exon 14 deletion. The exact eligibility criteria are not provided but typically include factors like age, overall health status, and the stage of cancer.

Inclusion Criteria

My cancer has a specific genetic change called MET exon 14 skipping.

I am not allergic to crizotinib or similar medications.

Patients must have met applicable eligibility criteria in the Master MATCH Protocol EAY131/ NCI-2015-00054 prior to registration to treatment subprotocol

Exclusion Criteria

I haven't had a heart attack or severe heart issues in the last 3 months and don't have major GI problems.

I am not taking any strong medication or consuming foods that affect certain liver enzymes.

I do not have severe lung scarring or diseases, except for past radiation pneumonitis.

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 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsy, radiologic evaluation, and blood sample collection throughout the study.

Up to 3 years

Every 2 cycles (8 weeks) for the first 26 cycles, then every 3 cycles (12 weeks)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs every 3 months for 2 years, then every 6 months for year 3.

3 years

Every 3 months for 2 years, then every 6 months for year 3

Treatment Details

Interventions

• Crizotinib

Trial Overview The trial is testing Crizotinib's effectiveness on cancers with MET exon 14 deletion. It's a phase II study to see if this tyrosine kinase inhibitor can stop cancer cells from growing by blocking certain enzymes and cutting off blood supply to tumors.

Participant Groups

Group I: Treatment (Crizotinib) Experimental Treatment 4 Interventions

Patients receive crizotinib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsy on study and undergo radiologic evaluation and blood sample collection throughout the study.

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

Crizotinib is an effective treatment for adults with ALK-positive advanced non-small cell lung cancer (NSCLC), showing significant improvements in progression-free survival and quality of life compared to standard chemotherapy in ongoing phase I/II and phase III studies involving previously treated patients.

The treatment is generally well tolerated, although it can cause liver transaminase elevations and neutropenia as common adverse events; however, the long-term survival benefit remains uncertain due to confounding factors in the data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Crizotinib: a review of its use in the treatment of anaplastic lymphoma kinase-positive, advanced non-small cell lung cancer. Frampton, JE.[2021]

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 has an oral bioavailability of about 43%, and while a high-fat meal slightly decreases its absorption, this effect is not clinically significant, indicating that it can be taken with food without major concerns.

In two phase I clinical studies involving healthy volunteers, crizotinib was found to be safe, with no serious adverse events reported and only mild side effects, such as diarrhea, suggesting it is well-tolerated in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of crizotinib absolute bioavailability, the bioequivalence of three oral formulations, and the effect of food on crizotinib pharmacokinetics in healthy subjects. Xu, H., O'Gorman, M., Boutros, T., et al.[2018]

Crizotinib is an effective small-molecule inhibitor targeting the ALK tyrosine kinase receptor and c-Met, showing significant activity against tumors with ALK rearrangements, particularly in non-small cell lung cancer (NSCLC).

In clinical studies, patients with ALK-positive NSCLC treated with crizotinib exhibited high response rates and prolonged progression-free survival, leading to its approval for advanced ALK-positive NSCLC in August 2011.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Crizotinib for the treatment of patients with advanced non-small cell lung cancer. Bowles, DW., Weickhardt, AJ., Doebele, RC., et al.[2021]

Crizotinib (XALKORI) is an effective treatment for patients with ALK-positive non-small cell lung cancer (NSCLC), showing an objective response rate of 61% in one trial and 50% in another, with median response durations of 48 and 42 weeks, respectively.

The drug was granted accelerated approval due to its high response rates and durability, and later received full approval after demonstrating improved progression-free survival in patients previously treated with platinum-based chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

U.S. Food and Drug Administration approval: crizotinib for treatment of advanced or metastatic non-small cell lung cancer that is anaplastic lymphoma kinase positive. Malik, SM., Maher, VE., Bijwaard, KE., et al.[2022]

Crizotinib (Xalkori) has been approved by the FDA for treating recurrent or refractory ALK-positive myofibroblastic tumors in both adults and children aged one year and older, highlighting its efficacy in this specific cancer type.

Common side effects include vision disorders and nausea in adults, while pediatric patients may experience a broader range of effects such as vomiting, diarrhea, and abdominal pain, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Indication for Cancer Drug Crizotinib. Aschenbrenner, DS.[2023]

Crizotinib, an ALK inhibitor, has been established as a new standard of care for advanced ALK-positive non-small cell lung cancer (NSCLC) due to its significant efficacy and favorable safety profile observed in phase I, II, and III trials.

Most adverse events associated with crizotinib are mild to moderate, and with proper monitoring and supportive care, dose interruptions can often be avoided, allowing patients to continue benefiting from the treatment even after initial disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of crizotinib therapy for ALK-rearranged non-small cell lung carcinoma: an expert consensus. Cappuzzo, F., Moro-Sibilot, D., Gautschi, O., et al.[2018]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Crizotinib: a review of its use in the treatment of anaplastic lymphoma kinase-positive, advanced non-small cell lung cancer. [2021]

2. 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]

3. England pubmed.ncbi.nlm.nih.gov

Evaluation of crizotinib absolute bioavailability, the bioequivalence of three oral formulations, and the effect of food on crizotinib pharmacokinetics in healthy subjects. [2018]

4. Spain pubmed.ncbi.nlm.nih.gov

Crizotinib for the treatment of patients with advanced non-small cell lung cancer. [2021]

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

U.S. Food and Drug Administration approval: crizotinib for treatment of advanced or metastatic non-small cell lung cancer that is anaplastic lymphoma kinase positive. [2022]

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

New Indication for Cancer Drug Crizotinib. [2023]

7. Ireland pubmed.ncbi.nlm.nih.gov

Management of crizotinib therapy for ALK-rearranged non-small cell lung carcinoma: an expert consensus. [2018]

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

Pharmacokinetic/pharmacodynamic modeling of crizotinib for anaplastic lymphoma kinase inhibition and antitumor efficacy in human tumor xenograft mouse models. [2022]