The CCG and its member offices cooperate with scientists across the NCI and around the world.
Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial (ALCHEMIST)
ALCHEMIST will screen up to 8,000 patients with early stage lung cancer for two genetic changes in their tumors:
- Changes in epidermal growth factor receptor (EFGR)
- Changes in anaplastic lymphoma receptor tyrosine kinase (ALK).
Following surgical resection of the tumor, screened patients will be treated with adjuvant standard of care treatment consisting of chemotherapy with or without radiation therapy. After completion of the standard adjuvant therapy, patients with tumors exhibiting either the EGFR mutations or the ALK gene rearrangements (approximately 15 percent) will be eligible to receive additional targeted inhibitors erlotinib and crizotinib respectively in placebo controlled trials.
The ALCHEMIST study is composed of three trials:
The study is open to patients through the NCI-funded National Clinical Trials Network (NCTN) of research institutions and clinics. The Alliance for Clinical Trials in Oncology is leading the screening and EGFR treatment components. The ECOG-ACRIN Cancer Research Group is leading the ALK treatment component. Members from all NCTN groups have participated in in developing ALCHEMIST.
Patients without genetic changes in the EGFR or ALK genes will be treated with the standard of care and monitored prospectively. Samples that are initially collected, as well as samples from any recurrent tumors from those patients, will be genetically analyzed to identify molecular changes associated with disease progression. DNA and RNA sequences and clinical data will be made available in the Genomic Data Commons (GDC). ALCHEMIST is jointly run and managed by CCG and the NCI Division of Cancer Treatment and Diagnosis (DCTD).
Cancer Genomics Cloud Pilots
Analyzing the enormous amount of cancer genomic data produced by CCG using local resources requires extensive and costly local infrastructure. To enable all researchers to perform computationally intensive genomic analyses, CCG collaborates with NCI’s Center for Biomedical Informatics & Information Technology (CBIIT) Cancer Genomics Cloud Pilots. The three Cloud Pilots, developed and implemented through contracts from the NCI, democratize access to data from CCG’s genomics programs. Currently, the Cloud Pilots host the TCGA dataset, which contains data on over 11,000 patients from across 33 types of cancer. Going forward, the NCI Genomic Data Commons (GDC) will provide the Cloud Pilots with an authoritative set of all of CCG’s molecular and clinical data. The Cloud Pilots will then make these data available in a secure and compliant cloud environment, while also delivering computational capabilities and tools that enable researchers to analyze their data alongside CCG data. By partnering with commercial clouds, the Cloud Pilots will also cut data storage costs and facilitate large-scale computation.
Clinical Trial Sequencing Project (CTSP)
NCI’s CCG and Division of Cancer Treatment and Diagnosis (DCTD) are engaged in a collaboration named CTSP. This project has launched out of a joint aspiration to promote the use of genomics in NCI-sponsored clinical trials of the National Clinical Trials Network (NCTN). CTSP’s goal is to elucidate the molecular basis of response and resistance to therapies studied. Biospecimens collected from NCI-sponsored NCTN clinical trials will undergo whole genome or whole exome sequencing in conjunction with transcriptome sequencing to identify genomic alterations important to the hypotheses stated in the proposals. The genomic and anonymized clinical data from CTSP will be made publically available in the GDC to benefit the cancer research community. The cancer types currently under study are breast cancer, renal cell carcinoma, and diffuse large B-cell lymphoma.
TAILORx: Trial Assigning Individualized Options for Treatment (TAILORx) is an NCI-sponsored clinical trial investigating whether some breast cancer patients may be treated effectively without undergoing chemotherapy, and if a gene expression test can help choose the best individualized treatment. CCG’s study of breast cancer tissue from TAILORx aims to illuminate the molecular basis of ER-positive, Her2-negative breast cancer response and recurrence, and to provide vital genomic information about breast cancer treatments and outcomes to the cancer research community. The trial enrolled over 10,000 women with estrogen receptor-positive (ER-positive), human epidermal growth factor-negative (Her2-negative) breast cancer that had not spread to the lymph nodes. Each patient’s tumor was evaluated with a gene expression test for the probability of cancer recurrence following surgical removal. The trial grouped patients based on the score obtained from the gene expression test, into low, middle, and high chance of recurrence. All patients with a high risk of recurrence received chemotherapy, as did randomly assigned middle-risk patients; low-risk patients received hormone therapy only and were spared chemotherapy. Initial results, published in the New England Journal of Medicine, indicate that low-risk women fare well when spared chemotherapy and that the gene expression test is a clinically helpful tool for determining the best treatment for individual patients.
Renal Cell Carcinoma
ECOG-ACRIN E2805 Trial of Renal-cell Carcinoma (RCC): CCG will receive tissue samples of renal cell carcinoma, the most common kidney cancer in adults, from a recent NCI-sponsored clinical trial that tested the effectiveness of two inhibitors of vascular endothelial growth factor (VEGF) in patients with high-risk, non-metastatic RCC. Abnormal activity of the VEGF pathway drives RCC by stimulating the development of blood vessels that provide nutrients to the tumor. Inhibition of VEGF has been shown to be effective for the treatment of advanced RCC that has metastasized to other areas of the body. However, patients with high-risk, non-metastatic disease treated with sunitinib or sorafenib, both VEGF inhibitors, received no benefit compared to patients who received a placebo following surgical removal of their tumors. CCG will analyze approximately 400 tissue samples from this trial of sunitinib and sorafenib to learn more about genomic drivers of RCC development, metastasis, and recurrence.
Diffuse Large B Cell Lymphoma
NCT00118209 Trial of Diffuse Large B Cell Lymphoma (DLBCL): CCG will perform a comprehensive molecular analysis of tissue samples of DLBCL, the most common adult non-Hodgkin lymphoma, from a Phase III clinical trial run by Cancer and Leukemia Group B. The trial, entitled “Rituximab and Combination Chemotherapy in Treating Patients With Diffuse Large B Cell Lymphoma” treated 430 DLBCL patients with rituximab, an antibody that targets B cells for destruction, in combination with one of two different chemotherapy regimens. By randomly assigning patients to either R-CHOP or Dose Adjusted-EPOCH-R, the study aims to establish which chemotherapy best complements rituximab in the treatment of DLBCL and to develop a molecular predictor of patient responses. The goal of CCG’s in-depth analysis of the DNA, RNA, and protein of DLBCL samples from this trial is to bolster the findings with rich molecular data and to add key information, including multi-platform analysis of DLBCL subtypes and predictors of tumor resistance.
Exceptional Responders Initiative
The Exceptional Responders Initiative aims to understand the genetic basis of some cancer patients' dramatically positive responses to particular drug therapies that are not effective for most other patients. This pilot study is characterizing the genomic profiles of 100 "exceptional responder" patients who were treated for a variety of different types of cancer by NCI-supported clinical trials or the oncology community. The study is sequencing tumor tissue, and normal tissue when available, from patients who responded to either investigational or FDA-approved chemotherapies or targeted molecular agents. The initiative’s scientists and clinicians are analyzing these genomic sequence data together with anonymized clinical information to identify molecular features that may explain why these patients responded exceptionally well. The study is sequencing the exomes, the areas of the genome that code for proteins, of all tumor tissue, and performing deep targeted sequencing using the FoundationOne® gene panel for qualifying cases. All findings, and the complete data set of exceptional responders, will be shared with controlled access protections though the Genomic Data Commons (GDC), enabling the research community to use the data to gain further insight into how certain types of cancer respond to treatment. The Exceptional Responders Initiative is a joint initiative of CCG and the Division of Cancer Treatment and Diagnosis (DCTD).
International Cancer Genome Consortium (ICGC)
The ICGC will generate a comprehensive catalog of genomic abnormalities (somatic mutations, abnormal expression of genes, epigenetic modifications) in tumors from 50 different cancer types or subtypes of clinical importance. This project strives to accelerate research that will provide insight about the causes and control of cancer. CCG programs that participate in ICGC include:
- The Cancer Genome Atlas (TCGA)
- Therapeutically Applicable Research to Generate Effective Treatments (TARGET)
- Cancer Genome Characterization Initiative (CGCI).
CCG is collaborating with ICGC for the Pan-Cancer Analysis of Whole Genomes (PCAWG) project. PCAWG is a joint effort to analyze whole genome data from 2,000 pairs of tumor and normal samples and integrate the results with clinical and other molecular data available on those same cases. Investigators from around the world will lead working groups to drive the analysis in a number of areas, such as mutation identification algorithms and patterns of structural variation in genomes. The data generated by whole genome sequencing will enable researcher to develop and examine a variety of hypotheses.
Learn more about PCAWG in the TCGA Leadership Update by Carolyn Hutter, Ph.D.