Date: 2014-08-18
Type of information: Initiation of development program
phase:
Announcement: initiation of the development program
Company: NCI (USA) Response Genetics (USA - CA) Pfizer (USA - NJ) Astellas Pharma (Japan)
Product: erlotinib, crizotinib
Action
mechanism: tyrosine kinase inhibitor
Disease: early-stage lung cancer
Therapeutic area: Cancer - Oncology
Country: USA
Trial
details: People enrolled in ALCHEMIST will need to undergo surgical removal of their tumors; have been diagnosed with lung adenocarcinoma or similar types of lung cancer as identified by examining the tissue; and will need to complete standard therapy after surgery, consisting of chemotherapy with or without radiation therapy as prescribed by their physician. The three component trials of ALCHEMIST are: • ALCHEMIST - Screening component (A151216 - Genetic Testing in Screening Patients With Stage IB-IIIA Non-small Cell Lung Cancer That Has Been or Will Be Removed by Surgery)– Coordinated by the Alliance for Clinical Trials in Oncology; Principal Investigators: Pasi A. Janne, M.D., Ph.D., and Geoffrey Oxnard, M.D., Dana-Farber Cancer Institute, Boston. This research trial studies genetic testing in screening patients with stage IB-IIIA non-small cell lung cancer that has been or will be removed by surgery. Studying the genes in a patient's tumor cells may help doctors select the best treatment for patients that have certain genetic changes. (NCT02194738) • ALCHEMIST - EGFR Treatment component (A081105 - Erlotinib Hydrochloride in Treating Patients With Stage IB-IIIA Non-Small Cell Lung Cancer That Has Been Completely Removed by Surgery (An ALCHEMIST Treatment Trial)) – Coordinated by the Alliance for Clinical Trials in Oncology; Principal Investigator: Ramaswamy Govindan, M.D., Washington University, St. Louis. This randomized phase III trial studies how well erlotinib hydrochloride compared to placebo works in treating patients with stage IB-IIIA non-small cell lung cancer that has been completely removed by surgery. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. (NCT02193282 ) • ALCHEMIST - ALK Treatment component (E4512 - Crizotinib in Treating Patients With Stage IB-IIIA Non-small Cell Lung Cancer That Has Been Removed by Surgery and ALK Fusion Mutations (An ALCHEMIST Treatment Trial))– Coordinated by ECOG-ACRIN; Principal Investigator: David E. Gerber, M.D., University of Texas Southwestern Medical Center at Dallas. This randomized phase III trial studies how well crizotinib works and compares it to placebo 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 ALK. Mutations, or changes, in ALK can make it very active and important for tumor cell growth and progression. Tumors with this mutation may respond to treatments that target the mutation, such as crizotinib. Crizotinib may stop the growth of tumor cells by blocking the ALK protein from working. It is not yet known if crizotinib may be an effective treatment for treating non-small cell lung cancer with an ALK fusion mutation. (NCT02201992)
In the ALCHEMIST screening trial, the surgically removed tissue will be tested in a central laboratory for certain genetic changes in two genes, ALK and EGFR. Participants with tumors found to harbor EGFR mutations or rearrangement of the ALK gene will then be referred to one of two randomized, placebo-controlled ALCHEMIST treatment trials. These studies will evaluate the value of adding therapy with specific agents targeted against two genetic alterations, erlotinib (EGFR) and crizotinib (ALK), in the post-operative setting. The FDA has approved these drugs for the treatment of patients with advanced forms of lung cancer whose tumors harbor the targeted genetic alterations. However, it is not known if these agents will be beneficial when administered to patients who are clinically free of disease. The goal of the trials is to determine whether erlotinib or crizotinib will prevent lung cancer recurrence, as well as prolong life, when used against tumors that carry specific mutations.
Latest
news: * On August 18, 2014, the NIH announced the launch of 3 integrated precision medicine trials. The Adjuvant Lung Cancer Enrichment Marker Identification andSequencing Trials, or ALCHEMIST, aims to identify early-stage lung cancer patients with tumors that harbor certain uncommon genetic changes and evaluate whether drug treatments targeted against those changes can lead to improved survival. ALCHEMIST is supported by the NCI, part of the National Institutes of Health, with coordination of the component trials by the Alliance for Clinical Trials in Oncology and the ECOG-ACRIN Cancer Research Group. All of the NCI-supported National Clinical Trials Network (NCTN) groups collaborated in the development of ALCHEMIST and are participating in the component trials. The goal of the trials is to determine whether erlotinib or crizotinib will prevent lung cancer recurrence, as well as prolong life, when used against tumors that carry specific mutations.
All screened participants, irrespective of the marker status of their tumors, will be followed for five years in the screening trial. All participants in ALCHEMIST will continue to receive the best care possible for their lung cancer. At the conclusion of the treatment trials, statisticians will analyze the survival of patients who received an additional genetically-targeted drug therapy versus patients who received standard therapy alone.
ALCHEMIST involves substantial collaborations with biotechnology and pharmaceutical partners. For the ALCHEMIST screening component, central laboratory testing for EGFR gene mutations and for the ALK gene rearrangement will be performed by Response Genetics. For the ALCHEMIST treatment trials, Pfizer will provide crizotinib under a clinical trials agreement with the ECOG-ACRIN Cancer Research Group. Astellas Pharma will provide erlotinib under a cooperative research and development agreement with NCI for the clinical development of erlotinib.
ALCHEMIST incorporates a number of other aspects of evolving clinical research and medical practice, including DNA sequencing and genomic analysis of tumor tissue, and possible additional genomic analysis at the time of lung cancer recurrence. Moreover, every participant enrolled in ALCHEMIST will also be studied for cancer risk characteristics, and their tumor tissue will be analyzed with advanced sequencing technologies in a research genomics initiative conducted by the NCI Center for Cancer Genomics (CCG). This research will capitalize on the foundation of CCG’s earlier effort, The Cancer Genome Atlas, which is a collaboration with the National Human Genome Research Institute, another component of NIH.
