| General information |
| Database: | DB00781 |
| Objective: | Oncogenic fusion genes consisting of EML4 and anaplastic lymphoma kinase (ALK) are present in a subgroup of non small cell lung cancers, representing 2 to 7% of such tumors. they explored the therapeutic efficacy of inhibiting ALK in such tumors in an earlyphase clinical trial of crizotinib (PF02341066), an orally available smallmolecule inhibitor of the ALK tyrosine kinase. |
| Authors: | Kwak EL, et al |
| Title: | Anaplastic lymphoma kinase inhibition in non small cell lung cancer. |
| Journal: | N Engl J Med. |
| Year: | 2010 |
| PMID: | 20979469 |
| Trial Design |
| Clinical Trial Id: | NCT00585195 |
| Agent: | crizotinib
|
| Target: | Hepatocyte growth factor receptor, ALK, ROS1
|
| Cancer Type: | non small cell lung cancer |
| Cancer Subtype: | non small cell lung cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | an openlabel, multicenter, twopartphase I trial |
| Key Patients Feature: | patients with advanced ALKpositive disease who were eligible for the clinical trial.Most of the patients had received previous treatment. |
| Biomarker: | ALK rearrangements |
| Biomark Analysis: | Patients with ALK rearrangements tended to be younger than those without the rearrangements, and most of the patients had little or no exposure to tobacco and had adenocarcinomas. |
| Control Group Info: | single arm |
| Treatment Info: | These patients were enrolled in an expanded cohort study instituted afterphase 1 dose escalation had established a recommended crizotinib dose of 250 mg twice daily in 28day cycles. Patients were assessed for adverse events and response to therapy. |
| Primary End Point: | ORR, 6month progression free survival |
| Secondary End Point: | NA |
| Patients Number: | 82 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 57% |
| Disease Control Rate: | 33% |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 6month progression free survival was 72%, with no median for the study reached. |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Grade 1 nausea and diarrhea were the most commonly reported side effects. Mild visual disturbances were reported by 34 patients (41%). |
| Conclusions: | The inhibition of ALK in lung tumors with the ALK rearrangement resulted in tumor shrinkage or stable disease in most patients. (Funded by Pfizer and others; ClinicalTrials.gov number, NCT00585195.). |