Crizotinib for Non-Small Cell Lung Cancer
Recruiting in Palo Alto (17 mi)
+1473 other locations
Overseen byDavid Gerber
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.12345
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.24678
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.12459
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.
See 27 more
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 OverviewThe 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
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm A (crizotinib)Experimental Treatment2 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 Control2 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Epic Care Partners in Cancer CareEmeryville, CA
Summit Cancer Care-MemorialSavannah, GA
Our Lady of the Lake Physicians Group - Medical OncologyBaton Rouge, LA
Michigan Breast Specialists-Grosse Pointe WoodsGrosse Pointe Woods, MI
More Trial Locations
Loading ...
Who Is Running the Clinical Trial?
ECOG-ACRIN Cancer Research GroupLead Sponsor
National Cancer Institute (NCI)Collaborator
References
Crizotinib: a new treatment option for ALK-positive non-small cell lung cancer. [2022]To review the characteristics and clinical trial data of crizotinib in ALK-positive non-small cell lung cancer (NSCLC).
Evaluation of crizotinib absolute bioavailability, the bioequivalence of three oral formulations, and the effect of food on crizotinib pharmacokinetics in healthy subjects. [2018]Crizotinib (Xalkori®) is an orally administered, selective, small-molecule, ATP-competitive inhibitor of the anaplastic lymphoma kinase (ALK) and mesenchymal epithelial transition factor/hepatocyte growth factor receptor tyrosine kinases, and has recently been approved for the treatment of ALK-positive non-small cell lung cancer. The absolute bioavailability of crizotinib, effect of a high-fat meal on crizotinib pharmacokinetics (PK), and bioequivalence of several oral formulations (powder in capsule [PIC], immediate-release tablet [IRT], and commercial formulated capsule [FC]) were evaluated in two phase I clinical studies involving healthy volunteers who received single doses of crizotinib. PK parameters for crizotinib and its metabolite, PF-06260182, were determined using non-compartmental methods. The absolute oral bioavailability of crizotinib was approximately 43%, with a slight decrease in crizotinib exposures (area under the plasma concentration-time profile and maximum plasma concentration) following a high-fat meal that was not considered clinically meaningful. The FC was bioequivalent to the clinical development IRT and PIC formulations. No serious adverse events were observed during either study and the majority of adverse events were mild, the most common being diarrhea. Single-dose crizotinib could be safely administered to healthy subjects.
Treatment of ALK-positive non-small cell lung cancer. [2018]Crizotinib (Xalkori), the first inhibitor of both anaplastic lymphoma kinase (ALK) and c-Met receptor kinases, has been approved in the United States, Korea, and other countries for the treatment of ALK-positive non-small cell lung cancer (NSCLC). This approval came within just 4 years of the discovery of rearrangements in the ALK gene in a subset of patients with NSCLC. Oral crizotinib 250 mg twice daily showed excellent efficacy in patients with advanced ALK-positive NSCLC, with objective response rates of 61% and 51% in ongoing phase I and II studies, respectively. Objective response rates of current standard, single-agent, second-line therapies are less than 10%. Median progression-free survival was 10 months (95% confidence interval, 8.2-14.7) in the phase I study expanded cohort and has yet to be reached in the phase II study; progression-free survival with current therapies is less than 3 months. Crizotinib was well tolerated; grade 1/2 gastrointestinal toxicity and visual disturbances were the most common adverse events. Patients in the phase II study reported improvements in fatigue, dyspnea, and cough, based on quality of life assessments. Phase III studies investigating crizotinib for the first- and second-line treatment of advanced ALK-positive NSCLC, versus current standards of care, are ongoing. Crizotinib represents a new standard of care for patients with ALK-positive NSCLC and highlights the importance of the role of the pathologist, as molecular profiling becomes a part of initial workups for newly diagnosed patients with NSCLC. This approach will ensure effective individualized treatment for patients with NSCLC.
Crizotinib: a review of its use in the treatment of anaplastic lymphoma kinase-positive, advanced non-small cell lung cancer. [2021]Crizotinib (Xalkori(®)) is an orally active, small molecule inhibitor of multiple receptor tyrosine kinases, including anaplastic lymphoma kinase (ALK), c-Met/hepatocyte growth factor receptor and c-ros oncogene 1. In the EU, crizotinib has been conditionally approved for the treatment of adults with previously treated, ALK-positive, advanced non-small cell lung cancer (NSCLC). This approval has been based on objective response rate and tolerability data from two ongoing phase I/II studies (PROFILE 1001 and PROFILE 1005); these results have been substantiated and extended by findings from an ongoing phase III study (PROFILE 1007) in patients with ALK-positive, advanced NSCLC who had received one prior platinum-based regimen. Those treated with crizotinib experienced significant improvements in progression-free survival, objective response rate, lung cancer symptoms and global quality of life, as compared with those treated with standard second-line chemotherapy (pemetrexed or docetaxel). The relative survival benefit with crizotinib is unclear, however, as the data are still immature and likely to be confounded by the high cross-over rate among chemotherapy recipients. Crizotinib treatment was generally well tolerated in the three PROFILE studies, with liver transaminase elevations and neutropenia being the most common grade 3 or 4 adverse events. Crizotinib is the standard of care in terms of the treatment of patients with ALK-positive, advanced NSCLC; while the current EU approval is for second (or subsequent)-line use only, the first-line use of the drug is being evaluated in ongoing phase III studies. Key issues relating to the use of crizotinib in clinical practice include identifying the small subset of eligible patients, the almost inevitable development of resistance and the high cost of treatment.
Crizotinib as a personalized alternative for targeted anaplastic lymphoma kinase rearrangement in previously treated patients with non-small-cell lung cancer. [2018]Crizotinib, the first clinically designed and synthesized as a tyrosine kinase inhibitor targeting mesenchymal-epithelial transition factor, indicating marked anticancer activity in patients with advanced, anaplastic lymphoma kinase-positive non-small-cell lung cancer, was approved by the US Food and Drug Administration in 2011. In this review, we focus on the efficacy of crizotinib compared with chemotherapy in advanced anaplastic lymphoma kinase-positive lung cancer and present the role of crizotinib as a personalized alternative in previously treated patients with non-small-cell lung cancer.
ALK-rearranged non-small cell lung cancers: how best to optimize the safety of crizotinib in clinical practice? [2018]Crizotinib (XALKORI™, Pfizer) is a tyrosine kinase inhibitor targeting ALK, MET and ROS1, currently approved for the treatment of adults with ALK-rearranged non-small-cell lung cancer. Optimizing the management of frequent crizotinib-related adverse events is crucial to ensure its continuous administration and reproduce the response and survival rates reported in clinical trials. Here, we propose some practical measures, which are mostly derived from the recommendations given to the investigators of the PROFILE 1001, 1005, 1007 and 1014 trials and are based on experience and scientific findings regarding the management of these disorders. While visual disturbances or bradycardia are frequent but benign, the severity of the cardiac and hepatic adverse events requires special attention potential to QT interval prolongations and to the monitoring of electrolyte levels and liver function, taking into account potential drug-drug interactions.
New Indication for Cancer Drug Crizotinib. [2023]The Food and Drug Administration has approved crizotinib (Xalkori) to treat adult and pediatric patients ages one year and older who have recurrent or refractory inflammatory anaplastic lymphoma kinase (ALK)-positive myofibroblastic tumors.The most common adverse effects in adults are vision disorders, nausea, and edema. The most common adverse effects in pediatric patients are vomiting, nausea, diarrhea, abdominal pain, rash, vision disorder, upper respiratory tract infection, cough, pyrexia, musculoskeletal pain, fatigue, edema, constipation, and headache.
FDA approval summary: crizotinib for the treatment of metastatic non-small cell lung cancer with anaplastic lymphoma kinase rearrangements. [2022]On August 26, 2011, crizotinib received accelerated approval for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that is ALK-positive as detected by a test approved by the U.S. Food and Drug Administration (FDA). Approval was based on two single-arm trials demonstrating objective response rates (ORRs) of 50% and 61% and median response durations of 42 and 48 weeks. On November 20, 2013, crizotinib received regular approval based on confirmation of clinical benefit in study A8081007, a randomized trial in 347 patients with ALK-positive advanced NSCLC who had previously received one platinum-containing regimen. Patients were assigned (1:1) to receive crizotinib 250 mg orally twice daily or standard of care (docetaxel or pemetrexed). The primary endpoint was progression-free survival (PFS) determined by independent radiology review; secondary endpoints were ORR and overall survival (OS). PFS was significantly longer in the crizotinib arm, with median PFS of 7.7 and 3.0 months in the crizotinib and chemotherapy arms, respectively, and a 46% absolute increase in ORR but no difference in OS between treatment arms at the interim analysis. The most common adverse drug reactions (>25%) in crizotinib-treated patients were vision disorders, nausea, diarrhea, vomiting, constipation, edema, elevated transaminases, and fatigue. The most serious toxicities of crizotinib were hepatotoxicity, interstitial lung disease or pneumonitis, and QT-interval prolongation. Crizotinib's rapid clinical development program (6 years from identification of ALK rearrangements in a subset of NSCLC to full FDA approval) is a model of efficient drug development in this new era of molecularly targeted oncology therapy.
Crizotinib for the treatment of patients with advanced non-small cell lung cancer. [2021]Crizotinib is a potent small-molecule inhibitor of ALK tyrosine kinase receptor (anaplastic lymphoma kinase; ALK) and hepatocyte growth factor receptor (HGF receptor, proto-oncogene c-Met). A range of tumors, including subsets of non-small cell lung cancer (NSCLC), anaplastic large cell lymphoma and inflammatory myofibroblastic tumors harbor an ALK rearrangement that leads to oncogenic activation of ALK. Crizotinib has demonstrated preclinical and clinical activity against such malignancies through inhibition of ALK, and patients harboring ALK- rearranged NSCLC have demonstrated high response rates and prolonged progression-free survival in phase I and II studies. In August 2011, crizotinib was approved for the treatment of advanced ALK-positive NSCLC.