Search Results - EGA European Genome-Phenome Archive

Molecular subsets in renal cancer determine outcome to checkpoint and angiogenesis blockade

We conducted integrated multi-omics evaluation of 823 tumors from advanced renal cell carcinoma (RCC) patients and identified molecular subsets associated with differential clinical outcomes to angiogenesis blockade alone or with a checkpoint inhibitor. Unsupervised transcriptomic analysis revealed six molecular subsets with distinct angiogenesis, immune, cell cycle, metabolism, and stromal programs. While sunitinib was effective in subsets with high angiogenesis, atezolizumab+bevacizumab improved clinical benefit in tumors with high T-effector and/or cell cycle transcription. Somatic mutations in PBRM1 and KDM5C associated with high angiogenesis and AMPK/Fatty acid oxidation gene expression, while CDKN2A/B and TP53 alterations were more prevalent in tumors with increased cell cycle and anabolic metabolism. Sarcomatoid tumors exhibited low prevalence of PBRM1 mutations and angiogenesis markers, frequent CDKN2A/B, BAP1 and TP53 alterations, and increased PD-L1 expression. These findings can be applied to molecularly stratify advanced RCC patients, explain improved outcomes of sarcomatoid tumors to checkpoint blockade, and develop personalized therapies.

Study EGAS00001004353

Genomic Profiling of Rare Tumors

Utilizing the rare and unique patient samples provided by Pattern Medicine, LLC, MD Anderson will molecularly characterize rare cancer samples, and potentially generate a collection of preclinical models to enable identification of novel therapeutic targets and concepts, as well as evaluation of innovative treatment strategies.

Study phs003916

Center for Common Disease Genomics (CCDG) - Cardiovascular: Multiethnic Cohort

The genetic basis of cardiovascular disease in individuals of non-European ancestry remains largely unknown. Availability of ethnically diverse study populations is essential to investigate the underlying causes of disease.The National Human Genome Research Institute (NHGRI) has funded the Centers for Common Disease Genomics (CCDG), a collaborative large-scale genome sequencing effort to comprehensively identify rare risk and protective variants contributing to multiple common disease phenotypes and to better understand the general principles of genomic architecture underlying common, complex, inherited diseases. The Multiethnic Cohort (MEC) of the University of Hawaii Cancer Center and the University of Southern California comprises primarily five ethnic groups: Caucasians, Japanese Americans, Native Hawaiians, African Americans and Latinos. This study contains whole genome sequence data derived from participants in the MEC cohort identified as having early onset coronary artery disease.

Study phs003499

NCTN: An Intergroup Phase III Randomized Controlled Trial Comparing Melphalan, Prednisone and Thalidomide (MPT) vs Melphalan, Prednisone and Lenalidomide (Revlimid) (MPR) in Multiple Myeloma Patients Who Are Not Candidates for High-Dose Therapy (E1A06)

Study ID: E1A06NCT Number: NCT00602641ECOG-ACRIN Cancer Research GroupSubmitted in collaboration with the NCTN/NCORP Data ArchiveTrial Title: NCTN: An Intergroup Phase III Randomized Controlled Trial Comparing Melphalan, Prednisone and Thalidomide (MPT) vs Melphalan, Prednisone and Lenalidomide (Revlimid) (MPR) in Multiple Myeloma Patients Who Are Not Candidates for High-Dose Therapy (E1A06)Trial Description: This randomized phase III trial studies melphalan and prednisone with thalidomide to see how well it works compared to melphalan and prednisone together with lenalidomide in treating patients with newly diagnosed multiple myeloma. Drugs used in chemotherapy, such as melphalan and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Thalidomide and lenalidomide may stop the growth of multiple myeloma by blocking blood flow to the cancer. It is not yet known whether melphalan and prednisone are more effective when given together with thalidomide or lenalidomide in treating multiple myeloma.Clinical data presented in the following publication(s):PMID 26157076Disease type(s): Hematopoietic Neoplasm/Myeloma - MyelomaClinical Dataset(s) included:NCT00602641-D1 (PMID 26157076): There are three datasets for E1A06's primary publication 26157076 (-D1 through -D3). This dataset contains baseline characteristics, overall survival, progression-free survival, stratification, response, treatment and maintenance duration, and quality of life assessment data. It includes all randomized patients according to assigned treatment. Unless otherwise indicated, blank fields indicate missing values.NCT00602641-D2 (PMID 26157076): There are three datasets for E1A06's primary publication 26157076 (-D1 through -D3). This dataset contains dosing information by visit. Unless otherwise indicated, blank fields indicate missing values.NCT00602641-D3 (PMID 26157076): There are three datasets for E1A06's primary publication 26157076 (-D1 through -D3). This dataset contains data for adverse events analyses and tables. Unless otherwise indicated, blank fields indicate missing values.You are encouraged to view the PDF data dictionaries found in the “Documents” tab of the dbGaP study page, which may contain additional information regarding the data or the associated publication(s).

Study phs004394

Lineage Heterogeneity and Plasticity in Lung Cancer

Our previous studies found lung cancer cells harboring amplification of lineage oncogenes are specifically dependent on their expression for survival. The need for lineage amplified genes in a subset of cancers suggests unique vulnerabilities in cancer cells that may be poised on the brink of survival. However, these amplifications represent only a minor subset of the two major subtypes of lung cancers. Therefore, this study focuses on the lineage factors that are essential during the development and control cell identity in adult cells, in the remaining subsets of lung cancers. Through genome-wide profiling of a histone marks, we identified ‘super-enhancers' (SE) on lineage-defining transcription factor genes. Subsequent hierarchical clustering of lung cancer samples identified SEs specific to subsets of lung cancers. We aim to understand the significance of factors defining the lineage state of the newly defined subsets of lung cancers.

Study phs004458

Genomics Studies of AML in Patients Older than 60 Years of Age (ECOG-ACRIN Cancer Research Group's Clinical Trial e3999)

Acute Myeloid Leukemia (AML) is a disease of old age with a median diagnosis age of 69 years (SEER data 2024). Despite progress in our field, as patients age, they suffer from worse clinical outcomes compared to younger patients. A better understanding of disease biology is needed to yield discoveries that will contribute to the identification of therapeutic vulnerabilities in this aged population, and in the long-term, result in improved survival rates. Although AML patients older than 60 are most of the patients diagnosed with this disease, few studies have solely focused on the molecular features of this disease in the aged population. This study aimed to discover the molecular features of AML patients older than 60 years of age. De-identified blood and bone marrow specimens investigated in the study were obtained from 199 AML patients enrolled in ECOG-ACRIN Cancer Research Group's e3999 clinical trial (NCT00046930). Exome capture was performed on DNA isolated from disease enriched cells and patient-matched lymphocytes as germline controls. The frequencies and co-occurrence of somatic events and features associated with clinical outcomes in this population were reported. Phenotypic data from this study cohort were submitted to the NCTN/NCORP Data Archive. It is hoped that this resource can be leveraged to address potential disease mechanisms and treatment vulnerabilities in AML patients over the age of 60.

Study phs003773

The Discovery and Validation of AML Prognostic Biomarkers

This study includes RNA-Seq and targeted DNA sequencing from a large collection of unsorted mononuclear cells (MNCs) and enriched viable leukemic blasts (VLBs) from bone marrow (BM) and peripheral blood (PBL) specimens collected at diagnosis from adult patients with acute myeloid leukemia (AML). Viable leukemic blasts were isolated using forward by side scatter, DAPI staining and fluorescently-labeled antibodies to CD45, CD34, CD38, and CD117. DNA and RNA were extracted using Qiagen AllPrep DNA/RNA Extraction kits. Transcriptome libraries were generated using KAPA Stranded RNA-Seq Library Preparation Kit after ribosomal RNA depletion with Roche RiboErase. Paired-end 75 bp reads were sequenced on either Illumina HiSeq 2500 (HiSeq) or NovaSeq 6000 (NovaSeq) instruments. RNA-Seq data were analyzed by the Fred Hutch Cancer Center Bioinformatics Shared Resource. STAR 2.7.1, with 2-pass mapping, was used to align reads to human reference genome GRCh37/hg19. Internal tandem duplication in FLT3 (FLT3-ITD) were identified via fragment analyses. DNA was sequenced using Illumina TruSight™ Myeloid Sequencing Panel and supplemented with in-house targeted MiSeq assays for CEBPA and NRAS exon 3 loci inadequately covered by TruSight™ platform on Illumina MiSeq instrument. Paired-end reads were first aligned to the human genome reference assembly (GRCh37/hg19) using Burrows-Wheeler Aligner (BWA, v0.7.12) and then, the resulting alignment data were processed according to the best practice of Genome Analysis Toolkit (GATK, v3.5).

Study phs002805

Blood and Marrow Clinical Trials Network (BMT CTN) A Phase III Randomized, Multicenter Trial Comparing Sirolimus/Tacrolimus With Tacrolimus/Methotrexate as Graft-versus-Host Disease Prophylaxis After HLA-Matched, Related Peripheral Blood Stem Cell Transplantation (BMT-CTN-0402-BioLINCC)

ObjectivesThe primary objective was to determine if the combination of tacrolimus and sirolimus (Tac/Sir) was more effective than tacrolimus and methotrexate (Tac/Mtx) in preventing acute graft-versus-host disease and early mortality after allogeneic related donor hematopoietic cell transplantation.BackgroundStem cell transplantation is a standard therapy for leukemia and myelodysplastic disorders. Recipients of human leukocyte antigen (HLA)-matched, related donor (MRD) stem cell transplants are at risk for a number of infections and complications. One of these complications is a condition known as acute graft-versus-host disease (GVHD). Recipients of HLA-MRD stem cell transplants for the treatment of myelodysplastic disorders and leukemia experience a 35% incidence of GVHD. Furthermore, GVHD contributes significantly to 1-year early treatment-related mortality (TRM) estimates of approximately 20%.The standard prophylaxis regimen for GVHD is a calcineurin inhibitor combined with methotrexate. Calcineurin inhibitors block calcineurin, a protein phosphatase that catalyzes some of the intracellular processes associated with T-lymphocyte activation. Inhibition is achieved by binding to immunophilins. The result is reduced production of interleukin-2 and reduced proliferation of T-cells. Methotrexate, an antineoplastic antimetabolite, has immunosuppressant properties that prevents the synthesis of tetrahydrofolate. Tetrahydrofolate is necessary for synthesis of thymidylate, an essential component of DNA. Of particular clinical concern is the theory that the injury caused by methotrexate to tissues could play a contributory role in initiation of the cytokine cascade associated with GVHD.The standard prophylaxis regimen for GVHD was established in the mid-1980s. Minor alterations to the standard regimen have shown limited effect on TRM outcomes in spite of the improvements that have been made to allogeneic hematopoietic cell transplantation (HCT) outcomes. Sirolimus, a rapamycin inhibitor, has been suggested as an alternative for methotrexate. Previous studies have suggested that sirolimus use results in decreased incidence of acute GVHD and treatment-related toxicity after HLA-MRD and unrelated donor transplantation, at the expense of higher rates of endothelial injury syndromes. Sirolimus has additional immunomodulatory properties that include effects on antigen-presenting cells, the thymus, and preservation of regulatory T-cell subsets after transplantation. The purpose of this study was to determine if sirolimus, in place of methotrexate, would produce improved outcomes in GVHD and TRM.ParticipantsEligible participants were 2 to 60 years of age, of either gender, and were undergoing transplantation for one of the following conditions: acute leukemia in remission, myelodysplastic disorder, or chronic myeloid leukemia in chronic or accelerated phase. All participants were required to have a 6/6 Class I HLA-A and B and molecular Class II DRB1 matched sibling donor medically able and willing to donate peripheral blood stem cells that also met institutional criteria for stem cell donation.Participants were excluded from participating in the trial for the following: prior allogenic or autologous transplant, HIV or another uncontrolled active infection, pregnant or breast-feeding, known allergy to sirolimus, requiring voriconazole at time of study entry, currently receiving another investigational drug (unless cleared by protocol officer or chair), or participants with a history of cancer.Participants were excluded from continuation for the following laboratory criteria if measured within 4 weeks of study entry: measured creatinine clearance 500mg/dL; forced vital capacity (FVC) or forced expiratory volume (FEV1) 45% in adults or A total of 304 participants were enrolled in the study. 151 participants were randomized to the tacrolimus/sirolimus (Tac/Sir) treatment, which 149 completed and 2 did not undergo transplantation. 153 participants were randomized to the tacrolimus/methotrexate (Tac/Mtx) treatment, which 152 completed and 1 did not undergo transplantation.DesignBMT 0402 was an interventional study with the purpose of determining the best combination of medications for the prevention of GVHD after HLA-MRD peripheral blood stem cell transplantation. Two GVHD prophylaxis conditioning regimens were tested: tacrolimus/sirolimus (Tac/Sir) and tacrolimus/methotrexate (Tac/Mtx). The study was Phase III, and designed to be multicenter, randomized, open label, and with parallel assignment treatment arms. Randomization occurred within 7 days of initiation of pretransplantation conditioning therapy, and was performed in a 1:1 ratio with the use of random block sites, stratified by transplantation center. The transplant physician selection of treatment occurred prior to participant's assignment to the study. All parties involved in the trial knew the treatment arm assigned to each participant.Participants received pretransplantation myeloablative conditioning with total body irradiation in combination with either cyclophosphamide or etoposide. Initially, a conditioning regimen comprised of myeloablative doses of busulfan with CY was permitted, however this was removed due to excess toxicity and veno-occulusive disease of the liver. The participants that received busulfan-based conditioning were not included in the primary outcome analyses. PBSC donors received filgrastim and underwent large volume apheresis with a goal of collecting 2 to 10 × 106/kg CD34+ stem cells. No graft manipulation was allowed prior to the infusion of the stem-cell product.For GVHD prophylaxis, tacrolimus was begun on day −3 for all participants at a dose of 0.02 mg/kg/day by continuous IV infusion, adjusted to maintain a serum concentration of 5 to 10 ng/mL. For participants in the Tac/Sir group, sirolimus was started on day −3 with a 12 mg oral loading dose, followed by daily oral doses of 4 mg, adjusted to maintain a serum trough concentration of 3 to 12 ng/mL. For participants in the Tac/Mtx group, methotrexate was IV administered on day +1 (15 mg/m2), +3, +6, and +11 (10 mg/m2 each day).The primary endpoint of grades II-IV acute GVHD-free survival was assessed 114 days from the time of randomization based on intention-to-treat. The study had 80% power to detect a 15% difference between the 2 prophylaxis strategies based on the standardized difference in Kaplan-Meier estimates with a 2-sided α of 5%. A committee of investigators blinded to GVHD prophylaxis assignment reviewed all case records, focusing on the incidence of acute and chronic GVHD, relapse, toxicity, and causes of death. Participants were followed for two years after transplantation for evaluation of secondary endpoints, which included cumulative incidence of acute GVHD, time to neutrophil and platelet engraftment, mucositis severity, rate of veno-occlusive disease, thrombotic microangiopathy infection, cytomegalovirus reactivation, treatment-related mortality, malignant disease relapse, all infections, overall survival, and time to discharge after transplant.ConclusionsParticipants who received Tac/Sir engrafted significantly earlier and had significantly less severe oropharyngeal mucositis after transplantation; however, no difference was observed in the primary end point of GVHD-free survival at 114 days post randomization between participants treated with Tac/Sir and Tac/Mtx (Cutler C. et al., Blood 2014).

Study phs004629

NCTN: TAILORx: Program for the Assessment of Clinical Cancer Tests: Trial Assigning Individualized Options for Treatment (PACCT-1)

Study ID: PACCT-1NCT Number: NCT00310180Trial Title: NCTN: Program for the Assessment of Clinical Cancer Tests (PACCT-1): Trial Assigning Individualized Options for Treatment: The TAILORx TrialTrial Description:This randomized phase III trial studies the best individual therapy for women who have node-negative, estrogen-receptor positive breast cancer by using a special test (Oncotype DX), and whether hormone therapy alone or hormone therapy together with combination chemotherapy is better for women who have an Oncotype DX recurrence score of 11-25. Estrogen can cause the growth of breast cancer cells. Hormone therapy may fight breast cancer by blocking the use of estrogen by the tumor cells or by lowering the amount of estrogen the body makes. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving hormone therapy together with more than one chemotherapy drug (combination chemotherapy) has been shown to reduce the chance of breast cancer recurrence, but the benefit of adding chemotherapy to hormone therapy for women with node-negative, estrogen-receptor positive breast cancer is small. New tests may provide information about which patients are more likely to benefit from chemotherapy. You are encouraged to view the PDF data dictionaries found in the "Documents" tab of the dbGaP study page, which may contain additional information regarding the data or the associated publication.ECOG-ACRIN Cancer Research GroupSubmitted in collaboration with the NCTN/NCORP Data ArchiveData presented in the following publication(s):PMID 29860917PMID 32271671Disease type(s): Breast Neoplasm - Breast Cancer - InvasiveAvailable Dataset(s):NCT00310180-D1 (PMID 29860917): This dataset contains the data published in the primary results publication for TAILORx (PACCT-1; NCT00310180; PMID 29860917). The dataset includes patient characteristics, OncoType Recurrence Score values, survival outcomes, and stratification variables used in the analyses presented in the publication. The data reflect the study database as of March 2, 2018. All patients who were registered to one of the arms are included.NCT00310180-D4 (PMID 32271671): There are three separate submissions for PMID 32271671, a publication analyzing the cognitive function among women with early breast cancer on ECOG-ACRIN trial PACCT-1. This dataset submission, NCT00310180-D4, contains additional clinical data in addition to those submitted in NCT00310180-D1 (for the trial's primary publication with PMID 29860917). Dataset NCT00310180-D5 contains the FACT-COG data. Dataset NCT00310180-D6 contains the FACT-G data. The data contained within variables identical to those presented in NCT00310180-D1 are not duplicated in this submission.NCT00310180-D5 (PMID 32271671): There are three separate submissions for PMID 32271671, a publication analyzing the cognitive function among women with early breast cancer on ECOG-ACRIN trial PACCT-1. This dataset submission, NCT00310180-D5, contains the FACT-COG data. Dataset NCT00310180-D4 contains additional clinical data in addition to those submitted in NCT00310180-D1 (for the trial's primary publication with PMID 29860917). Dataset NCT00310180-D6 contains the FACT-G data. The data contained within variables identical to those presented in NCT00310180-D1 are not duplicated in this submission.NCT00310180-D6 (PMID 32271671): There are three separate submissions for PMID 32271671, a publication analyzing the cognitive function among women with early breast cancer on ECOG-ACRIN trial PACCT-1. This dataset submission, NCT00310180-D6, contains the FACT-G data. Dataset NCT00310180-D4 contains additional clinical data in addition to those submitted in NCT00310180-D1 (for the trial's primary publication with PMID 29860917). Dataset NCT00310180-D5 contains the FACT-COG data. The data contained within variables identical to those presented in NCT00310180-D1 are not duplicated in this submission.Forthcoming Dataset(s): NCT00310180-D2, NCT00310180-D3

Study phs004260

NCTN: A Randomized Phase III Trial of Three Different Regimens of CPT-11 Plus 5-Fluorouracil and Leucovorin Compared to 5-Fluorouracil and Leucovorin in Patients with Advanced Adenocarcinoma of the Colon and Rectum (N9741)

Study ID: N9741 NCT Number: NCT00003594 Alliance for Clinical Trials in Oncology Submitted in collaboration with the NCTN/NCORP Data Archive Trial Title: NCTN: A Randomized Phase III Trial of Three Different Regimens of CPT-11 plus 5-Fluorouracil and Leucovorin compared to 5-Fluorouracil and Leucovorin in Patients with Advanced Adenocarcinoma of the Colon and Rectum (N9741) Trial Description: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known which regimen of combination chemotherapy is most effective in treating advanced colorectal cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of various combination chemotherapy regimens in treating patients who have advanced, recurrent, or metastatic colorectal cancer that cannot be treated with surgery or radiation therapy. Clinical data presented in the following publication(s): PMID 14665611 Disease type(s): Gastrointestinal Neoplasm - Colorectal Cancer Clinical dataset(s) included: NCT00003594-D1 (PMID 14665611): The NCT00003594-D1 dataset is one of 4 datasets associated with PubMed ID 14665611. This dataset contains information regarding patient-level information including eligibility, treatment arm, baseline characteristics, grade 4 and 5 toxicity data, and best response. It also includes information to analyze overall survival and time to progression. NCT00003594-D2 (PMID 14665611): The NCT00003594-D2 dataset is one of 4 datasets associated with PubMed ID 14665611. This dataset contains information per patient, per cycle regarding dosing, reasons for treatment delays, and overall response assessment status. NCT00003594-D3 (PMID 14665611): The NCT00003594-D3 dataset is one of 4 datasets associated with PubMed ID 14665611. This dataset contains information per patient, per cycle, per adverse event during treatment. NCT00003594-D4 (PMID 14665611): The NCT00003594-D4 dataset is one of 4 datasets associated with PubMed ID 14665611. This dataset contains information per patient regarding end of treatment timing and reason. Additional genomic data are available for this trial under phs001290. You are encouraged to view the PDF data dictionaries found in the “Documents” tab of the dbGaP study page, which may contain additional information regarding the data or the associated publication(s).

Study phs004259

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