Crizotinib for Cancer with ALK Genetic Changes

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: ALK inhibitors, CYP3A4 drugs

Disqualifiers: Non small cell lung cancer, ALCL, interstitial lung disease, pneumonitis, 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

5 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 ALK rearrangement. Crizotinib may stop the growth of cancer cells by blocking the ALK protein which may be needed for 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 does not specify if you must stop all current medications, but you cannot use drugs or foods that strongly affect CYP3A4, an enzyme that processes many medications. If you're on such medications, you may need to stop them before joining the trial.

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

Crizotinib has shown significant effectiveness in treating patients with ALK-positive non-small cell lung cancer (NSCLC), with high response rates and longer periods without disease progression compared to other treatments. It was approved for use after studies demonstrated its ability to shrink tumors and improve survival in these patients. ^{1 2 3 4 5}

Is crizotinib safe for humans?

Crizotinib, also known as Xalkori, is generally well-tolerated but can cause side effects like vision problems, nausea, and swelling. More serious issues can include heart and liver problems, so regular monitoring is important. ^{6 7 8 9 10}

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

Crizotinib is unique because it specifically targets and inhibits the ALK (anaplastic lymphoma kinase) and c-Met (hepatocyte growth factor receptor) proteins, which are involved in the growth of certain cancers. It is taken orally and has shown significant effectiveness in treating ALK-positive non-small cell lung cancer, offering improved progression-free survival and quality of life compared to standard chemotherapy. ^{4 11 12 13 14}

Research Team

Alice T Shaw

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

This trial is for patients with various cancers that have a specific genetic change called ALK rearrangement. They must not have non-small cell lung cancer or certain lymphomas, no history of interstitial lung disease, and cannot be allergic to crizotinib. Prior treatments with ALK inhibitors disqualify them, as do untreated brain metastases or those on certain drugs affecting liver enzymes.

Inclusion Criteria

My recent ECG showed no significant heart issues.

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

My cancer has an ALK gene change.

Exclusion Criteria

My brain metastases are stable, treated, or not needing treatment.

I have never had interstitial lung disease or pneumonitis.

You are allergic to crizotinib or similar drugs.

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. Follow-up occurs 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 trial tests Crizotinib's effectiveness in shrinking or stopping the growth of cancers with the ALK genetic change. It's a phase II study where all participants receive Crizotinib to see how well it works against these types of cancer cells.

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

In a study of 106 patients with ALK-positive non-small cell lung cancer, 6.5% exhibited primary resistance to crizotinib, resulting in a median progression-free survival of only 1.2 months, compared to 47.0 months for long-term responders.

Patients who received next-generation ALK inhibitors after crizotinib progression had significantly better survival outcomes than those who only received supportive care, highlighting the potential for improved treatment strategies in this resistant population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical features and outcomes of ALK rearranged non-small cell lung cancer with primary resistance to crizotinib. Ma, D., Zhang, Y., Xing, P., et al.[2020]

Crizotinib is an effective treatment for patients with ALK-positive non-small-cell lung cancer (NSCLC), showing significant clinical benefits and leading to its early approval by the USFDA in 2011.

Despite its effectiveness in inducing remissions and prolonging patient survival, there are concerns about emerging resistance to crizotinib therapy, highlighting the need for ongoing research and development of new treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Crizotinib: A comprehensive review. Sahu, A., Prabhash, K., Noronha, V., 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]

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-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]

In a study of 36 ALK-positive metastatic NSCLC patients treated with crizotinib, neutropenia was associated with significantly improved progression-free survival (PFS), with a median PFS of 31.9 months compared to 12.8 months for those without neutropenia.

The study suggests that while other adverse events like hepatic or cardiac toxicities did not impact PFS, neutropenia could serve as a potential predictor for better treatment outcomes in patients receiving crizotinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictive role of neutropenia under crizotinib treatment in ALK-rearranged nonsmall cell lung cancer patients: A single-institution retrospective analysis. Gürsoy, P., Çakar, B., Nart, D., et al.[2022]

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 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]

References

1. Singapore pubmed.ncbi.nlm.nih.gov

Clinical features and outcomes of ALK rearranged non-small cell lung cancer with primary resistance to crizotinib. [2020]

2. India pubmed.ncbi.nlm.nih.gov

Crizotinib: A comprehensive review. [2022]

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

Pharmacokinetics of crizotinib in NSCLC patients. [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

Treatment of ALK-positive 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. India pubmed.ncbi.nlm.nih.gov

Predictive role of neutropenia under crizotinib treatment in ALK-rearranged nonsmall cell lung cancer patients: A single-institution retrospective analysis. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Managing treatment-related adverse events associated with Alk inhibitors. [2022]

9. 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]

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

New Indication for Cancer Drug Crizotinib. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Final results of the large-scale multinational trial PROFILE 1005: efficacy and safety of crizotinib in previously treated patients with advanced/metastatic ALK-positive non-small-cell lung cancer. [2022]

12. 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]

13. 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]

14. France pubmed.ncbi.nlm.nih.gov

ALK inhibitors: a new targeted therapy in the treatment of advanced NSCLC. [2022]