Clinical Trials

This research trial studies neuropsychological (learning, remembering or thinking) and behavioral outcomes in children and adolescents with cancer by collecting information over time from a series of tests.

This research trial studies kidney tumors in younger patients. Collecting and storing samples of tumor tissue, blood, and urine from patients with cancer to study in the laboratory may help doctors learn more about changes that occur in deoxyribonucleic acid (DNA) and identify biomarkers related to cancer.

RAS mutations result in upregulation of the mitogen-activated protein kinase (MAPK) pathway and are thought to be key driver mutations in many malignancies. . The importance of RAS mutations is underscored by its high prevalence in human malignancies. Data from the COSMIC database indicates that RAS, which has three highly homologous isoforms KRAS, N-RAS, and HRAS, is mutated in approximately 30% of human malignancies. Mutations in NRAS are found in approximately 8% of human cancers. While most frequently seen in melanomas, NRAS mutations are seen in many other solid malignancies including colorectal, gastric, thyroid, uterine endometrial, lung, among others. Despite enormous efforts from both academia and industry, successful targeting of RAS mutated malignancies has been an elusive goal. Clinical trials testing numerous strategies, including farnesyl transferase inhibitors and combined MEK/PI3K inhibition, have failed to produce widespread, clinically meaningful results. Interestingly, preclinical testing demonstrates that NRAS mutated cell lines are more sensitive to MEK inhibitor than KRAS mutated cell lines. For example, a study of lung cancer cell lines demonstrated that five of six NRAS mutant cell lines were sensitive to the MEK inhibitors. Consistent with in vitro observations, the most successful effort in targeting RAS mutations has been seen in NRAS mutated melanoma. In an open label phase 2 study, treatment of 117 patients with NRAS mutated melanoma with the MEK inhibitor binimetinib resulted in an overall response rate of 14.5% with PFS of 3.6 months and OS of 12.2 months14. In a smaller phase 2 trial of binimetinib, six (20%; 95% CI 8-39%) of 30 patients with NRAS-mutated melanoma had a partial response.

This study gathers health information for the Project: Every Child for younger patients with cancer. Gathering health information over time from younger patients with cancer may help doctors find better methods of treatment and on-going care.

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. Study Arms: 1) Experimental: Arm A (crizotinib) Patients receive crizotinib on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. 2) Placebo Comparator: Arm B (placebo) Patients receive placebo on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

The purpose of this study is to compare the effect on your cancer of using either olaparib by itself or the combination of cediranib and olaparib to the usual chemotherapy given for your cancer (carboplatin and paclitaxel; carboplatin and gemcitabine; or carboplatin and pegylated liposomal doxorubicin [PLD]). Any of these different approaches could shrink your cancer but could also cause side effects. This study will allow the researchers to learn whether giving olaparib by itself or giving the combination of cediranib and olaparib is better, the same, or worse than the usual chemotherapy by observing both the effect of these treatments on your cancer as well as any side effects that may be experienced. Both olaparib and cediranib have already been tested for safety; however, they are not part of the standard approach. Olaparib by itself has been approved by the Food and Drug Administration (FDA) for women with advanced ovarian cancer and a mutation in either BRCA1 or BRCA2 (these are genes in which mutations can be inherited that have been linked to a higher risk of developing cancers, including breast and ovarian cancer) who have received three or more prior treatments for their cancer. The use of olaparib in the setting of platinum-sensitive recurrent ovarian cancer like yours is still being studied and is not FDA-approved. The combination of olaparib and cediranib is still being studied and is not yet FDA-approved. There will be about 450 people taking part in this study. About 5-10 people will be put on this study at this site.

PRIMARY OBJECTIVES: I. To evaluate the disease-free survival (DFS) of patients with stage III-IV squamous cell carcinoma of the head and neck (SCCHN) and disruptive p53 mutations after primary surgical resection followed by postoperative radiotherapy (PORT) alone or PORT with concurrent cisplatin. SECONDARY OBJECTIVES: I. To evaluate the DFS of patients with stage III-IV SCCHN and non-disruptive p53 mutations after primary surgical resection followed by PORT alone or PORT with concurrent cisplatin. II. To evaluate the DFS of patients with stage III-IV SCCHN and p53 wild type after primary surgical resection followed by PORT alone or PORT with concurrent cisplatin. III. To evaluate toxicities of PORT alone or PORT with concurrent cisplatin. IV. To evaluate p53 mutation as a predictive biomarker of survival benefit given post-operative concurrent radiation and cisplatin. V. To identify potential genomic alterations in addition to TP53 mutations that may be developed to a novel treatment approach. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM A: Patients undergo intensity-modulated radiation therapy (IMRT) once daily (QD) 5 days a week for 6 weeks in the absence of disease progression or unacceptable toxicity. ARM B: Patients undergo IMRT QD 5 days a week and receive cisplatin intravenously (IV) over 1-2 hours weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6 months for 3 years and then every 12 months for 7 years.

**This study is closed to new patients** This randomized phase II/III trial studies how well standard of care therapy with stereotactic radiosurgery and/or surgery works and compares it to standard of care therapy alone in treating patients with breast cancer that has spread to one or two locations in the body (limited metastatic) that are previously untreated. Standard of care therapy comprising chemotherapy, hormonal therapy, biological therapy, and others may help stop the spread of tumor cells. Radiation therapy and/or surgery is usually only given with standard of care therapy to relieve pain; however, in patients with limited metastatic breast cancer, stereotactic radiosurgery, also known as stereotactic body radiation therapy, may be able to send x-rays directly to the tumor and cause less damage to normal tissue and surgery may be able to effectively remove the metastatic tumor cells. It is not yet known whether standard of care therapy is more effective with stereotactic radiosurgery and/or surgery in treating limited metastatic breast cancer.

This randomized phase II trial studies how well cisplatin works with or without veliparib in treating patients with triple-negative breast cancer and/or BRCA mutation-associated breast cancer that has come back (recurrent) or has or has not spread to the brain (brain metastases). Drugs used in chemotherapy, such as cisplatin, 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. PARPs are proteins that help repair DNA mutations. PARP inhibitors, such as veliparib, can keep PARP from working, so tumor cells can't repair themselves, and they may stop growing. It is not yet known if cisplatin is more effective with or without veliparib in treating patients with triple-negative and/or BRCA mutation-associated breast cancer.

This phase III trial studies combination chemotherapy and atezolizumab to see how well it works compared with combination chemotherapy alone in treating patients with stage III colon cancer and deficient deoxyribonucleic acid (DNA) mismatch repair. Drugs used in combination chemotherapy, such as oxaliplatin, leucovorin calcium, and fluorouracil, 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. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving combination chemotherapy with atezolizumab may work better than combination chemotherapy alone in treating patients with colon cancer.