Crizotinib for Non-Small Cell Lung Cancer

Recruiting at 1473 trial locations

Overseen By Eric C. McGary

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: ECOG-ACRIN Cancer Research Group

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Pregnancy, Cardiac arrhythmia, Interstitial lung disease, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

This randomized phase III trial studies how well crizotinib works in treating patients with stage IB-IIIA non-small cell lung cancer that has been removed by surgery and has a mutation in a protein called anaplastic lymphoma kinase (ALK). Mutations, or changes, in ALK can make it very active and important for tumor cell growth and progression. Crizotinib may stop the growth of tumor cells by blocking the ALK protein from working. Crizotinib may be an effective treatment for patients with non-small cell lung cancer and an ALK fusion mutation.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does mention that you cannot use medications that are known to strongly affect a specific liver enzyme (CYP3A4). You can continue low-dose methotrexate for non-cancer conditions.

What data supports the effectiveness of the drug Crizotinib for non-small cell lung cancer?

Crizotinib has shown excellent effectiveness in treating ALK-positive non-small cell lung cancer, with high response rates and longer progression-free survival compared to standard therapies. Patients experienced significant improvements in symptoms and quality of life, making it a new standard of care for this type of cancer. ^{1 2 3 4 5}

Is crizotinib safe for humans?

Crizotinib, also known as Xalkori, is generally safe for humans, but it can cause some side effects. Common side effects include vision problems, nausea, diarrhea, and swelling. Serious side effects can include liver problems, lung disease, and heart rhythm changes, so monitoring by a doctor is important. ^{2 4 6 7 8}

What makes the drug Crizotinib unique for treating non-small cell lung cancer?

Crizotinib is unique because it specifically targets and inhibits the anaplastic lymphoma kinase (ALK) gene rearrangement found in some non-small cell lung cancers, offering a personalized treatment option that can improve progression-free survival and quality of life compared to standard chemotherapy. ^{1 2 4 5 9}

Research Team

David Gerber

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

This trial is for adults who've had surgery to remove stage IB-IIIA non-small cell lung cancer and have an ALK gene mutation. They should not be pregnant or breastfeeding, must not have other serious illnesses, and cannot have had certain cancers within the last 5 years. Participants need a good performance status (able to carry out daily activities) and can't be on drugs that strongly affect liver enzymes.

Inclusion Criteria

Your AST and ALT blood levels are not more than 2.5 times the upper limit of normal.

Your ANC is at least 1500/mm^3.

My cancer has a specific genetic change (ALK fusion) confirmed by a special test.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive crizotinib orally twice daily on days 1-21, with treatment repeating every 21 days for up to 2 years

Up to 2 years

Observation

Participants undergo observation without active treatment

Up to 2 years

Follow-up

Participants are monitored for overall survival and disease-free survival, with follow-up every 6 months if less than 4 or 5 years from study entry, and every 12 months if 5-10 or 6-10 years from study entry

Up to 10 years

Treatment Details

Interventions

• Crizotinib (Tyrosine Kinase Inhibitor)

Trial Overview The study is testing if crizotinib, which blocks a protein called ALK involved in tumor growth, is effective after surgery in patients with specific genetic changes in their lung cancer. It's compared against regular follow-up without this drug. Patients are randomly assigned to either receive crizotinib or undergo clinical observation.

Participant Groups

Group I: Arm A (crizotinib) Experimental Treatment 2 Interventions

Patients receive crizotinib PO BID on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Group II: Arm B (observation) Active Control 2 Interventions

Patients undergo observation.

Crizotinib is already approved in Japan, Canada for the following indications:

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?

ECOG-ACRIN Cancer Research Group

Lead Sponsor

Trials

122

Recruited

160,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Crizotinib is an effective targeted therapy for patients with ALK-positive non-small cell lung cancer (NSCLC), showing response rates of 50-57% and a duration of response of 6-10 months in early clinical trials.

The drug has been FDA-approved due to its ability to improve response rates and progression-free survival in ALK-positive NSCLC patients, although it may cause mild to moderate side effects such as visual disturbances and gastrointestinal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Crizotinib: a new treatment option for ALK-positive non-small cell lung cancer. O'Bryant, CL., Wenger, SD., Kim, M., et al.[2022]

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 (Xalkori) has shown excellent efficacy in treating advanced ALK-positive non-small cell lung cancer (NSCLC), with objective response rates of 61% in phase I and 51% in phase II studies, significantly outperforming standard therapies that have response rates below 10%.

The treatment is well tolerated, with common side effects being mild gastrointestinal issues and visual disturbances, and it has led to improvements in patients' quality of life, including reduced fatigue and cough.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of ALK-positive non-small cell lung cancer. Bang, YJ.[2018]

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 a targeted therapy that has shown significant anticancer activity in patients with advanced anaplastic lymphoma kinase-positive non-small-cell lung cancer, leading to its FDA approval in 2011.

This review highlights crizotinib's efficacy as a personalized treatment option compared to traditional chemotherapy for patients who have already undergone treatment for non-small-cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Crizotinib as a personalized alternative for targeted anaplastic lymphoma kinase rearrangement in previously treated patients with non-small-cell lung cancer. Guo, L., Zhang, H., Shao, W., et al.[2018]

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 (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 is an effective treatment for ALK-positive non-small cell lung cancer (NSCLC), showing a significant improvement in progression-free survival (PFS) compared to standard chemotherapy, with a median PFS of 7.7 months versus 3.0 months in the chemotherapy group during a study of 347 patients.

While crizotinib has a high response rate and was approved based on its efficacy, it also has notable side effects, including vision disorders and hepatotoxicity, highlighting the importance of monitoring for serious adverse reactions during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA approval summary: crizotinib for the treatment of metastatic non-small cell lung cancer with anaplastic lymphoma kinase rearrangements. Kazandjian, D., Blumenthal, GM., Chen, HY., et al.[2022]

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]

References

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

Crizotinib: a new treatment option for ALK-positive non-small cell lung cancer. [2022]

2. 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]

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

Treatment of ALK-positive non-small cell lung cancer. [2018]

4. 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]

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

Crizotinib as a personalized alternative for targeted anaplastic lymphoma kinase rearrangement in previously treated patients with non-small-cell lung cancer. [2018]

6. 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]

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

New Indication for Cancer Drug Crizotinib. [2023]

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

FDA approval summary: crizotinib for the treatment of metastatic non-small cell lung cancer with anaplastic lymphoma kinase rearrangements. [2022]

9. Spain pubmed.ncbi.nlm.nih.gov

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