Crizotinib for Lung Cancer

Overseen By Natasha Leighl, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University Health Network, Toronto

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Brain metastases, Long QT syndrome, 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: 9

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called crizotinib (also known as Xalkori) to evaluate its effectiveness against non-small cell lung cancer that has metastasized. It specifically targets patients with changes in the ROS1 or MET genes. Participants are grouped according to their specific gene changes. Individuals with stage IV non-small cell lung cancer and a confirmed ROS1 rearrangement or MET mutation may be suitable for this trial. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of participants.

Do I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you cannot take medications that are strong inhibitors or inducers of CYP3A4. If you're on such medications, you may need to stop them before joining the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that crizotinib is generally well-tolerated in people with certain gene changes in non-small cell lung cancer. For patients with MET changes, studies indicate that crizotinib's side effects are usually mild and similar to those observed in other studies.

In patients with ROS1 changes, crizotinib also demonstrates a good safety record. Several studies have tested it, finding that its side effects are usually predictable and not too serious.

Overall, research supports the safety of crizotinib for both MET and ROS1 groups. Crizotinib is already approved for treating ALK- or ROS1-positive lung cancer, which increases confidence in its safety. However, as with any medication, discussing possible side effects with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Crizotinib is unique because it targets specific genetic changes in non-small cell lung cancer (NSCLC), setting it apart from traditional chemotherapy and immunotherapy. Unlike other treatments, Crizotinib specifically inhibits the activity of the MET and ROS1 gene alterations, which are known to drive cancer growth. This precision targeting means that Crizotinib can potentially offer more effective treatment with fewer side effects for patients with these specific genetic profiles. Researchers are excited because targeting these mutations could lead to better outcomes and personalized treatment options for people with advanced NSCLC.

What is the effectiveness track record for crizotinib in treating ROS1 or MET mutated non-small cell lung cancer?

In this trial, patients with non-small cell lung cancer (NSCLC) will be assigned to different arms based on specific genetic changes. For those with MET gene changes, such as MET-amplification or MET-activating mutation (exon 14), crizotinib has proven effective in previous studies by targeting these alterations, which occur in about 3% to 4% of these cancers. Another arm of the trial will focus on patients with changes in the ROS1 gene, where crizotinib has also shown promise. It has been effective and safe for treating ROS1-positive NSCLC in both early and later stages. Overall, crizotinib is a well-established treatment for certain lung cancer gene changes, offering hope for targeting these specific genetic alterations. ^{2 3 4 6 7}

Who Is on the Research Team?

Natasha Leighl, M.D.

Principal Investigator

Princess Margaret Cancer Centre

Are You a Good Fit for This Trial?

This trial is for adults over 18 with advanced non-small cell lung cancer that has spread and have specific gene changes (ROS1 or MET). They must be able to take oral meds, not have serious GI issues affecting drug absorption, use birth control, and have a life expectancy over 12 weeks. Can't join if they've had certain recent treatments or conditions like untreated brain metastases or heart rhythm problems.

Inclusion Criteria

Not pregnant

I can take care of myself but might not be able to do heavy physical work.

Have the ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

I have no significant side effects from previous cancer treatments.

I haven't had chemotherapy, targeted therapy, or radiotherapy in the last 4 weeks.

I am taking medication that strongly affects liver enzyme CYP3A4.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Several visits (in-person)

Study Drug Period

Participants take the study drug crizotinib and have tests and procedures done about once a week for safety and research purposes

Varies

Weekly visits (in-person)

End of Study Drug Visit

Participants return to the clinic for an end of study drug visit about 28 days after their last dose to have tests and procedures done for safety and research purposes

4 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with radiological imaging every 8 weeks until disease progression or start of new treatment

Until disease progression or new treatment

Every 8 weeks (in-person)

Long-term Follow-up

Study nurse calls participants approximately every 3 months to check on the status of their health

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Crizotinib

Trial Overview The study tests Crizotinib's effectiveness on lung cancer with ROS1 rearrangement or MET mutation/amplification. It's a phase 2 trial where participants receive Crizotinib to see how well it works against these genetic variations of the disease.

How Is the Trial Designed?

Group I: ROS1 Rearrangement Experimental Treatment 1 Intervention

Patients with stage IV or incurable non-squamous non-small cell lung cancer with a documented ROS1 rearrangement will be assigned to this arm.

Group II: MET-amplification Experimental Treatment 1 Intervention

Patients with stage IV or incurable non-squamous non-small cell lung cancer with a documented MET-amplification will be assigned to this arm.

Group III: MET-activating Mutation (exon 14) Experimental Treatment 1 Intervention

Patients with stage IV or incurable non-squamous non-small cell lung cancer with a documented MET-activating mutation (exon 14) will be assigned to this arm.

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?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Published Research Related to This Trial

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 oral treatment for patients with non-small cell lung cancer (NSCLC) that have the EML4-ALK rearrangement, showing promising disease control rates in clinical trials.

The drug has an acceptable safety profile and is currently available in France under temporary use authorization, indicating its recognized therapeutic potential for this specific cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Crizotinib: a targeted therapy in advanced ALK-positive non-small cell lung cancer]. Toffart, AC., Sakhri, L., Moro-Sibilot, D.[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 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 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, 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]

In a study of 65 ALK-positive advanced NSCLC patients who had previously failed crizotinib treatment, second-generation ALK inhibitors showed satisfactory efficacy, with alectinib demonstrating a 12-month progression-free survival (PFS) rate of 61.0% compared to 54.5% for ceritinib.

Alectinib was associated with a significantly lower incidence of central nervous system (CNS) progression and showed higher efficacy in patients whose crizotinib treatment failure was due to intolerance, indicating its potential advantages in specific patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective study of alectinib versus ceritinib in patients with advanced non-small-cell lung cancer of anaplastic lymphoma kinase fusion in whom crizotinib treatment failed. Kuo, CS., Tung, PH., Huang, AC., et al.[2021]

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]

Citations

1. jto.org jto.org/article/S1556-0864(21)01710-X/fulltext

Crizotinib in Patients With MET-Amplified NSCLC In patients with MET exon 14-altered NSCLC, reported objective responses to MET inhibition do not seem to be influenced by the absence, presence ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9771320/

Crizotinib efficacy and safety in patients with advanced ... This real-life data confirms efficacy and safety of crizotinib in the treatment of advanced NSCLC harboring MET alteration. Keywords: alteration ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8500676/

Antitumor Activity of Crizotinib in Lung Cancers Harboring a ... MET exon 14 alterations are identified in 3 to 4% of non-small cell lung cancers (NSCLCs) and less frequently in other cancers. These drivers are notable in ...

4. aacrjournals.org aacrjournals.org/clincancerres/article/30/23/5323/750203/Safety-Efficacy-and-Biomarker-Analysis-of

Safety, Efficacy, and Biomarker Analysis of Crizotinib in MET ... MET mutations, present in 3% to 4% of advanced non–small cell lung cancer cases, correlate with poor survival. Despite known sensitivity to c- ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.3108

Phase II study of crizotinib in patients with MET ... We demonstrate clinical activity using crizotinib across tumors in patients with METampand METex14. In METex14, differentiating true pathogenic variants from ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2016.34.15_suppl.108

Efficacy and safety of crizotinib in patients (pts) with ... Crizotinib has antitumor activity in pts with MET exon 14-altered NSCLC. The drug has a generally tolerable AE profile, consistent with that previously ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1525730422000134

Safety of MET Tyrosine Kinase Inhibitors in Patients With ... MET TKIs are tolerable treatment options for patients with METex14 skipping NSCLC, an older population for whom chemo- or immuno-therapy may not be an ...