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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the effectiveness of crizotinib, a medication that blocks certain enzymes and blood vessels crucial for cancer growth, in patients with specific genetic changes in their cancer. It specifically targets cancers with the MET exon 14 deletion, a particular genetic mutation. Suitable candidates for this trial have cancers with this genetic change and have not previously taken similar drugs. Participants will take crizotinib in cycles and undergo regular check-ups, including tumor biopsies and blood tests. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant cancer research.

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.

Is there any evidence suggesting that crizotinib is likely to be safe for humans?

Research has shown that crizotinib is generally well-tolerated by patients with certain types of cancer. Studies have included patients taking crizotinib for ALK-positive or ROS1-positive tumors, similar to those in this trial. In these studies, the most common side effects included vision problems, nausea, diarrhea, vomiting, and swelling, which were usually manageable.

More than 300 patients have taken crizotinib in earlier studies, providing a good understanding of its safety. Some patients experienced more serious effects, such as liver problems or lung inflammation, but these were less common. Since crizotinib is already approved for use in other cancers, there is a solid understanding of its safety in humans. Prospective participants should discuss any concerns with their healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Crizotinib is unique because it specifically targets certain genetic mutations found in some cancers, like ALK (anaplastic lymphoma kinase) and ROS1 gene rearrangements. This precision targeting is different from traditional chemotherapy, which attacks rapidly dividing cells but doesn't differentiate between healthy and cancerous ones. Researchers are excited about crizotinib because it can potentially reduce tumor size and slow cancer progression with fewer side effects, offering a more tailored and potentially more effective treatment option for patients with these specific genetic markers.

What evidence suggests that crizotinib might be an effective treatment for cancer with MET exon 14 deletion?

Research has shown that crizotinib, the treatment under study in this trial, effectively treats certain cancers, particularly those with specific genetic changes like ALK-positive non-small cell lung cancer (NSCLC). Studies have found that crizotinib can shrink tumors in about 60% of patients with this cancer type. One study found an overall response rate of 70.6%, with patients experiencing a median progression-free survival of 14.5 months, meaning the cancer did not worsen during and after treatment for this period. Crizotinib blocks enzymes that cancer cells need to grow and spread, and it may also prevent tumors from forming new blood vessels. This makes it a promising option for treating cancers with MET exon 14 deletion genetic changes. ^{6 7 8 9 10}

Who Is on the Research Team?

David S Hong

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 (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 (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 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 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, 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6613511/

Impact of crizotinib on long-term survival of ALK-positive ... The OS data of our study was highly consistent with that of PROFILE 1014, in which the survival probability at 4 years with crizotinib was 56.6%. CBPD might ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0169500224003507

Efficacy and safety of crizotinib in the treatment ... Meta-analysis of 14 crizotinib aNSCLC RWE studies yielded a pooled ORR of 70.6 %, median rwPFS of 14.5 mo, and OS of 40.2 mo. •. The real-world safety and ...

3. cancer.gov cancer.gov/types/lung/research/crizotinib

Crizotinib for Advanced Non-Small Cell Lung Cancer - NCI Results from an open-label phase III trial of 343 patients show that crizotinib is effective as first-line therapy for patients with advanced ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1408440

First-Line Crizotinib versus Chemotherapy in ALK-Positive ... In phase 1 and 2 studies, crizotinib treatment resulted in objective tumor responses in approximately 60% of patients with ALK-positive NSCLC ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.24.00581

Lorlatinib Versus Crizotinib in Patients With Advanced ALK ... After 5 years of follow-up, lorlatinib continued to show superior efficacy over crizotinib in patients with advanced ALK-positive non–small cell ...

6. xalkori.pfizerpro.com xalkori.pfizerpro.com/

XALKORI® (crizotinib) Official HCP Website | Safety Info Find info on XALKORI® (crizotinib), an Rx option for patients with metastatic NSCLC whose tumors are ALK-positive or ROS1-positive. See risks & benefits.

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2017/202570s021lbl.pdf

XALKORI (crizotinib) - accessdata.fda.gov The data described below is based primarily on 343 patients with ALK-positive metastatic NSCLC who received XALKORI 250 mg twice daily from 2 open-label, ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35042152/

Final efficacy and safety data, and exploratory molecular ... Final efficacy and safety data, and exploratory molecular profiling from the phase III ALUR study of alectinib versus chemotherapy in crizotinib-pretreated ALK ...

9. ema.europa.eu ema.europa.eu/en/documents/product-information/xalkori-epar-product-information_en.pdf

Xalkori, INN-crizotinib - EMA There are no safety or efficacy data of crizotinib treatment in ALK-positive ALCL paediatric patients below 3 years of age or ALK-positive IMT paediatric ...

10. mayoclinic.org mayoclinic.org/drugs-supplements/crizotinib-oral-route/description/drg-20075084

Crizotinib (oral route) - Side effects & dosage Crizotinib is an antineoplastic (cancer) agent. It interferes with the ... Safety and efficacy have not been established. Geriatric. Appropriate studies ...