1. What is the purpose of the ALCHEMIST trials?
ALCHEMIST- the Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trials – represents three integrated, precision medicine trials that are designed to identify people with early-stage lung cancer who have tumors that harbor EGFR and ALK gene alterations and evaluate whether drug treatments targeted against those molecular changes can lead to improved survival compared to current standard of care therapy alone (e.g., chemotherapy with or without radiotherapy after complete surgical resection as prescribed by a participant’s treating physician).
2. What are the three component trials of ALCHEMIST?
All participants in the trials will have received the current standard of care (e.g., surgical removal of their tumor followed by post-operative chemotherapy and or chemotherapy with radiation therapy) as prescribed by their treating physician.
3. Who is eligible to enroll in ALCHEMIST?
Men and women with certain types of lung cancer diagnosed at an early stage (tumor staged as IB that is greater than or equal to 4 centimeters in size, stage II, or stage IIIA) who are planning to undergo, or have undergone, complete surgical removal of their tumor are eligible to enroll in the ALCHEMIST screening trial. Those participants whose tumors are found to harbor certain genetic alterations (EGFR gene mutations or an ALK gene rearrangement) will then be referred to the appropriate ALCHEMIST treatment trial. Those treatment trials will evaluate drugs targeted against the specific genetic alterations in patients who have completed the standard therapy prescribed by their treating physician after surgery (usually chemotherapy with or without radiotherapy).
The types of lung cancer that participants must have to be eligible for ALCHEMIST are those that are likely to harbor the EGFR and ALK gene alterations. There are three main types of lung cancer:
NSCLC can be further divided into two major subtypes: squamous and non-squamous, based on differences in size, shape, and chemical make-up of the cells when examined under a microscope. It is the non-squamous type of NSCLC that is most likely to harbor the EGFR and ALK gene alterations and people with this type of lung cancer may be eligible for ALCHEMIST. This category represents about 60 percent of all lung cancers and includes adenocarcinoma, large cell carcinoma and a few other sub-types, such as adenosquamous carcinoma. About 10 percent of people in the United States with this category of lung cancer will have tumors with alterations in the EGFR gene and 5 percent will have rearrangements in the ALK gene.
4. What do the ALCHEMIST trials involve?
In the ALCHEMIST screening trial, tissue from the participant’s surgically removed tumor will be tested in a central laboratory for genetic changes in the epidermal growth factor receptor (EGFR) gene and anaplastic lymphoma kinase (ALK) gene. Abnormalities in these genes lead to tumor growth. Participants with tumors found to harbor these genetic alterations will be referred to the appropriate ALCHEMIST treatment trials.
ALCHEMIST will screen about 6,000 to 8,000 participants at hundreds of sites across the United States over 5 to 6 years in order to identify those with EGFR and ALK alterations in their tumors that may be eligible for the treatment trials. Each of the treatment trials will enroll about 400 patients but both combined will enroll 800 patients. Those participants with tumors that do not have these genetic alterations will continue to be followed on the ALCHEMIST screening trial for up to 5 years.
All participants in ALCHEMIST (the screening and treatment trials) will also be studied for cancer risk characteristics and their tumor tissue and blood samples will be further analyzed in basic research studies conducted by the NCI Center for Cancer Genomics (CCG).
5. What are the molecular tests used in ALCHEMIST and how will the cost of these tests be covered?
Tumor tissue from participants will be tested in a central facility for EGFR gene mutation and ALK gene rearrangement at Response Genetics, Inc., Los Angeles, a commercial CLIA-certified laboratory. EGFR genotyping will be performed by sequencing a certain part of the gene (the pieces defined as exons 18-21) and the test for the ALK rearrangement will be performed using the FDA-approved Vysis ALK break-apart probe. Results are expected to be provided to the treating physician within 14 business days of submission so that they can be used to determine eligibility for the treatment trials. The costs of these molecular tests for ALCHEMIST are being covered by the NCI.
6. What are the primary objectives of the trials?
The primary objectives of the ALCHEMIST trials are twofold:
7. What treatments will be evaluated in the ALCHEMIST treatment trials?
Participants with tumors found to harbor EGFR mutations or rearrangements in the ALK gene will be referred to the ALCHEMIST treatment trials evaluating specific drugs targeted against these genetic alterations, erlotinib and crizotinib, respectively. Participants enrolled on these treatment trials will be randomized to receive either the targeted agent or placebo.
The U.S. Food and Drug Administration (FDA) has approved erlotinib for the treatment of certain patients with advanced forms of lung cancer. Also, the FDA has approved the use of crizotinib in the treatment of advanced NSCLC in people whose tumors harbor the ALK gene rearrangement. However, it is not known if these drugs will be beneficial for those with early-stage lung cancer.
8. What is randomization and why is it necessary in the treatment trials?
Randomization is like flipping a coin. The treatment will be assigned by chance. This procedure is commonly used in clinical trials when new treatment approaches are being tested, and when there is uncertainty about the best treatment approach. Participants with early-stage lung cancers with the EGFR gene mutation will be referred to the treatment trial evaluating erlotinib and will be randomly assigned to receive erlotinib or a placebo because the benefit of erlotinib is uncertain in this group. Likewise, participants with early-stage lung cancers with an ALK gene rearrangement will be referred to the treatment trial evaluating crizotinib and will be randomly assigned to receive crizotinib or placebo because the benefit of crizotinib is uncertain in this group. In all cases, a participant will already have received any standard therapy (usually chemotherapy with or without radiation) prescribed by their treating physician.
9. How are the drugs for the ALCHEMIST treatment trials being provided?
The costs of the drugs for the ALCHEMIST treatment trials are being covered by the pharmaceutical company partners on the trials. Pfizer, New York City, will be providing crizotinib under a Clinical Trials Agreement with the ECOG-ACRIN Cancer Research Group. Astellas Pharma US, Inc., Northbrook, Illinois, will be providing erlotinib under a Cooperative Research and Development Agreement with NCI for the clinical development of erlotinib.
10. What treatment would normally be given to someone who did not participate in the ALCHEMIST trials?
The standard treatment for people with this type of early-stage lung cancer, after complete surgical removal of their tumor, is usually chemotherapy with or without radiation with no additional therapy.
11. Who is conducting the trial?
ALCHEMIST is supported by the National Cancer Institute (NCI), part of the National Institute of Health (NIH), with coordination of the component trials by the Alliance for Clinical Trials in Oncology and the ECOG-ACRIN Cancer Research Group. All of the U.S. NCI-supported adult National Clinical Trials Network (NCTN) groups have collaborated in the development of ALCHEMIST and are participating in the component trials, including SWOG and the NRG Oncology Group. These groups include networks of researchers, physicians, and health care professions at public and private institutions across the United States. They conduct clinical trials on all types of adult cancers.
In addition to the institutions belonging to the NCTN, ALCHEMIST will be open to all institutions and sites that participate in the NCI Community Oncology Research Program (NCORP).