Crizotinib for Non-Small Cell Lung Cancer

Recruiting at 1505 trial locations

Overseen By Tatjana Kolevska, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

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 All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: Unknown

Duration: Up to 2 years

168 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of crizotinib (also known as Xalkori) for individuals with non-small cell lung cancer that surgery has removed. The focus is on patients whose cancer cells have an ALK protein mutation, which crizotinib aims to block to halt cancer growth. Participants will either take crizotinib or undergo observation without active treatment to compare outcomes. This trial suits those who have undergone surgery to remove stage IB-IIIA non-small cell lung cancer and have an ALK mutation. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

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 ALK-positive non-small cell lung cancer. Studies have found that over 90% of patients experienced a reduction in tumor size, indicating effective drug action. A review of several studies reported that crizotinib is safe to use, with most patients not experiencing serious side effects.

While some side effects may occur, they are usually manageable and not severe enough to stop treatment. Patients should discuss any concerns with their doctors, but current evidence suggests that crizotinib is safe for treating this type of lung cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Crizotinib is unique because it specifically targets a genetic abnormality in non-small cell lung cancer (NSCLC) known as ALK (anaplastic lymphoma kinase) rearrangements. While traditional treatments for NSCLC often involve chemotherapy or radiation, crizotinib works by inhibiting the ALK protein, which can slow or even stop the growth of cancer cells. Researchers are excited about crizotinib because it offers a targeted therapy option that could be more effective and potentially have fewer side effects compared to conventional chemotherapy. This targeted approach means it could provide significant benefits to patients with ALK-positive NSCLC.

What evidence suggests that crizotinib might be an effective treatment for non-small cell lung cancer?

Research has shown that crizotinib, which participants in this trial may receive, is very effective for patients with ALK-positive non-small cell lung cancer. In studies, over 90% of patients experienced either tumor shrinkage or halted growth. Crizotinib blocks the ALK protein, preventing cancer cell growth. It has also proven safe for patients, offering a promising treatment option. ^{1 2 3 6 7}

Who Is on the Research Team?

David Gerber

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

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.

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 1-21, 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

What Are the Treatments Tested in This Trial?

Interventions

• Crizotinib

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.

How Is the Trial Designed?

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 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?

ECOG-ACRIN Cancer Research Group

Lead Sponsor

Trials

122

Recruited

160,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

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 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 (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 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 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 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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5832290/

Real-world outcomes in patients with ALK-positive non-small ... Crizotinib, for example, has been shown in clinical studies to be associated with tumour reduction or stabilization in 90% of alk+ patients, with response ...

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

Efficacy and safety of crizotinib in the treatment ... Crizotinib is safe and effective in treating ROS1-rearranged aNSCLC in first and later lines of therapy based on RWE.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3936578/

Activity and safety of crizotinib in patients with ALK-positive ... In the ALK-positive lung cancer population within this study, crizotinib showed marked efficacy, with tumour shrinkage in over 90% of patients ...

4. 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 ...

5. pfizer.com pfizer.com/news/press-release/press-release-detail/pfizer_presents_overall_survival_data_of_xalkori_in_patients_with_alk_positive_advanced_non_small_cell_lung_cancer

Pfizer Presents Overall Survival Data of XALKORI in ... Results indicated a numerical improvement in OS for patients treated with first-line XALKORI compared with chemotherapy, though this difference ...

6. 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- ...

7. annalsofoncology.org annalsofoncology.org/article/S0923-7534(25)04788-X/fulltext

final overall survival analysis of the phase III ALEX study Overall, 149 patients died: 76/152 (50.0%) in the alectinib arm and 73/151 (48.3%) in the crizotinib arm. Median OS was 81.1 months [95% CI 62.3 ...