Metastatic Colorectal Carcinoma

This phase III trial compares hepatic arterial infusion (HAI) (pump chemotherapy) in addition to standard of care chemotherapy versus standard of care chemotherapy alone in treating patients with colorectal cancer that has spread to the liver (liver metastases) and cannot be removed by surgery (unresectable). HAI uses a catheter to carry a tumor-killing chemotherapy drug called floxuridine directly into the liver. HAI is already approved by the Food and Drug Administration (FDA) for use in metastatic colorectal cancer to the liver, but it is only available at a small number of hospitals, and most of the time it is not used until standard chemotherapy stops working. Standard chemotherapy drugs 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. Adding HAI to standard chemotherapy may be effective in shrinking or stabilizing unresectable colorectal liver metastases.

This phase IIb trial tests the effect of HRX215 in treating patients with colorectal cancer that has spread from where it first started to the liver (liver metastasis) after undergoing a portal vein embolization (PVE). Currently, surgery to remove the tumor (hepatectomy) remains the only potential treatment for cure. However, less than 30% of patients are considered resectable (can be removed by surgery) at the time of diagnosis. The risk of liver failure and other complications rise with larger areas liver that is removed during surgery. Therefore, the potential for surgery is determined by the amount of liver that will remain after resection. PVE is a standard strategy to increase the potential for resection. A PVE is a procedure that blocks the portal vein (a blood vessel that carries blood to the liver) to prevent flow of blood to the tumor. HRX215 targets and binds to MKK4, a protein found on liver cells plays a part in cellular growth and prevents liver repair and regrowth of cells and tissue. Blocking the activity of MKK4 may help prevent liver failure, protect liver cells and improve liver mass. Giving HRX215 after a PVE may help improve the rate of liver regrowth and increase the likelihood of hepatectomy in patients with colorectal liver metastasis.

This phase I trial tests the safety, side effects, and best dose of ZEN003694 in combination with the usual treatment with capecitabine in treating patients with cancer that has spread from where it first started (primary site) to other places in the body (metastatic) or cannot be removed by surgery (unresectable) and that it has progressed on previous standard treatment. ZEN003694 is an inhibitor of a family of proteins called the bromodomain and extra-terminal (BET). It may prevent the growth of tumor cells that over produce BET protein. Capecitabine is in a class of medications called antimetabolites. It is taken up by cancer cells and breaks down into fluorouracil, a substance that kills cancer cells. Giving ZEN003694 in combination with capecitabine may be safe in treating patients with metastatic or unresectable solid tumors.

This phase II trial compares the impact of subcutaneous (SC) nivolumab given in an in-home setting to an in-clinic setting on cancer care and quality of life. Currently, most drug-related cancer care is conducted in clinic type centers or hospitals which may isolate patients from family, friends and familiar surroundings for many hours per day. This separation adds to the physical, emotional, social, and financial burden for patients and their families. Traveling to and from medical facilities costs time, money, and effort and can be a disadvantage to patients living in rural areas, those with low incomes or poor access to transport. Studies have shown that cancer patients often feel more comfortable and secure being cared for in their own home environments. SC nivolumab in-home treatment may be safe, tolerable and/or effective when compared to in-clinic treatment and may reduce the burden of cancer and improve the quality of life in cancer patients.

This study will investigate the tumor-associated vasculature of patients with solid tumors. The investigators will use a technology known as intravital microscopy (IVM) in order to visualize in real-time the vessels associated with solid tumors. The IVM observations may determine if an individual patient's tumor vessels would be amenable to receiving systemic therapy, based on the functionality of the vessels.

This is a first-in-human, Phase 1, non-randomized, multicenter, open-label clinical study designed to investigate the safety, tolerability, dosimetry, biodistribution, and pharmacokinetics (PK) of \[225Ac\]-FPI-2068, \[111In\]-FPI-2107, and FPI-2053 in metastatic and/or recurrent solid tumors (HNSCC, NSCLC, mCRC, PDAC, GC, RCC).

This phase II trial studies how well low dose, reduced frequency nivolumab works in treating patients with cancer that cannot be removed by surgery (unresectable) or that has spread from where it first started (primary site) to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Nivolumab is a type of immune checkpoint inhibitor (ICI). ICIs have revolutionized the treatment of numerous cancers with remarkable improvement in participant outcomes. However, accessibility of ICIs is extremely poor on a global scale, mainly due to high costs. Previous research has suggested that these drugs can be given at lower doses and reduced frequency than their approved dosing regimens, with similar results. Giving nivolumab at a lower dose and less often may help reduce the cost of therapy, improve immunotherapy accessibility, and therefore improve survival outcomes globally.

This trial compares cryoablation combined with stereotactic body radiation therapy to stereotactic body radiation therapy alone to see how well they work in treating patients with pain from cancer that has spread to the bones (bone metastases). Bone is a common site of metastasis in advanced cancer, and bone metastases often result in debilitating cancer-related pain. The current standard of care to treat painful bone metastases is radiation therapy alone. However, many patients do not get adequate pain relief from radiation therapy alone. Another type of therapy that may be used to provide pain relief from bone metastases is cryoablation. Cryoablation is a procedure in which special needles are inserted into the tumor site. These needles grow ice balls at their tips to freeze and kill cancer cells. The goal of this trial is to compare how well cryoablation in combination with radiation therapy works to radiation therapy alone when given to cancer patients to provide pain relief from bone metastases.

This study is being done to collect tissue samples to test how accurately a tumor response platform, Elephas, can predict clinical response across multiple types of immunotherapies, chemoimmunotherapy and tumor types.

This phase I trial tests the safety, side effects, and best dose of intraperitoneal oxaliplatin and fluorouracil in treating patients with colorectal cancer that has spread to the peritoneal cavity (peritoneal metastasis). Oxaliplatin is in a class of medications called platinum-containing antineoplastic agents. It damages the cell's DNA and may kill cancer cells. Fluorouracil stops cells from making DNA and it may kill cancer cells. Both oxaliplatin and fluorouracil are approved by the Food and Drug Administration to treat patients with colorectal cancer, however administration of these drugs directly into the area between the muscles and organs in the abdomen (intraperitoneal) for the treatment of peritoneal metastases is experimental. Giving oxaliplatin and fluorouracil directly into the peritoneal space may be a safe and effective way of treating patients with peritoneal metastases from colorectal cancer.

This trial evaluates the treatment response of colorectal cancer that has spread to the liver (liver metastases) using intravoxel incoherent motion diffusion weighted imaging (IVIM DWI). IVIM DWI is new kind of imaging scan that may help measure changes in disease before and after chemotherapy in patients with colorectal liver metastases.

This phase I trial studies the side effects of pressurized intraperitoneal aerosol chemotherapy (PIPAC) in treating patients with ovarian, uterine, appendiceal, stomach (gastric), or colorectal cancer that has spread to the lining of the abdominal cavity (peritoneal carcinomatosis). Chemotherapy drugs, such as cisplatin, doxorubicin, oxaliplatin, leucovorin, fluorouracil, mitomycin, and irinotecan, 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. PIPAC is a minimally invasive procedure that involves the administration of intraperitoneal chemotherapy. The study device consists of a nebulizer (a device that turns liquids into a fine mist), which is connected to a high-pressure injector, and inserted into the abdomen (part of the body that contains the digestive organs) during a laparoscopic procedure (a surgery using small incisions to introduce air and to insert a camera and other instruments in the abdominal cavity for diagnosis and/or to perform routine surgical procedures). Pressurization of the liquid chemotherapy through the study device results in aerosolization (a fine mist or spray) of the chemotherapy intra-abdominally (into the abdomen). Giving chemotherapy through PIPAC may reduce the amount of chemotherapy needed to achieve acceptable drug concentration, and therefore potentially reduces side effects and toxicities.

This phase III trial studies how well pressurized intraperitoneal aerosolized chemotherapy (PIPAC) with mitomycin works versus (vs) standard chemotherapy (leucovorin calcium, fluorouracil, and irinotecan hydrochloride \[FOLFIRI regimen\] plus bevacizumab) in treating patients with appendix or colorectal cancer that cannot be removed by surgery (unresectable) and has spread from where it first started (primary site) to the abdominal cavity (peritoneal metastases). PIPAC is a new therapeutic approach that is minimally invasive, does not require surgery (laparotomy), and can be frequently repeated. Chemotherapy is delivered as a pressurized mist directly inside the abdominal cavity (peritoneum) during a minimally invasive surgery called a laparoscopy. The pressure helps the chemotherapy absorb into the cancer tissue and spread more evenly. Mitomycin is an antibiotic used as a chemotherapy drug. It stops or slows the growth of cancer cells and other rapidly growing cells by damaging their deoxyribonucleic acid (DNA). Standard chemotherapy drugs, such as those in the FOLFIRI regimen, are given via infusion into a vein (intravenously), and 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. Another standard intravenous drug, bevacizumab, is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Giving mitomycin via PIPAC in combination with the standard FOLFIRI regimen, with or without bevacizumab, may work better than standard FOLFIRI plus bevacizumab alone in treating patients with unresectable appendix or colorectal cancer with peritoneal metastases.

This phase II trial studies how well radiation therapy works for the treatment of gastrointestinal cancer that are spreading to other places in the body (metastatic). Radiation therapy uses high energy x-rays to kill cancer cells and shrink tumors. This trial is being done to determine if giving radiation therapy to patients who are being treated with immunotherapy and whose cancers are progressing (getting worse) can slow or stop the growth of their cancers. It may also help researchers determine if giving radiation therapy to one tumor can stimulate the immune system to attack other tumors in the body that are not targeted by the radiation therapy.

The goal of this clinical trial is to learn if the OATD-02 administration (orally) in monotherapy is safe and has the pharmacodynamic potential to restore and enhance tumour responses to immunotherapy through increased arginine levels or intrinsic anti-tumour activity in participants with advanced metastatic colorectal cancer, ovarian cancer, renal cancer or pancreatic cancer.

The purpose of this study was to investigate the effect of only local radical treatment of liver metastases combined with systematic treatment in the treatment of patients with multiple organ metastases of colorectal cancer, whether it can benefit the prognosis and explore the risk factors related to the prognosis.

This phase II trial tests how well CPI-613 (devimistat) in combination with hydroxychloroquine (HCQ) and 5-fluorouracil (5-FU) or gemcitabine works in patients with solid tumors that may have spread from where they first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that have not responded to chemotherapy medications (chemorefractory). Metabolism is how the cells in the body use molecules (carbohydrates, fats, and proteins) from food to get the energy they need to grow, reproduce and stay healthy. Tumor cells, however, do this process differently as they use more molecules (glucose, a type of carbohydrate) to make the energy they need to grow and spread. CPI-613 works by blocking the creation of the energy that tumor cells need to survive, grow in the body and make more tumor cells. When the energy production they need is blocked, the tumor cells can no longer survive. Hydroxychloroquine is a drug used to treat malaria and rheumatoid arthritis and may also improve the immune system in a way that tumors may be better controlled. Fluorouracil is in a class of medications called antimetabolites. It works by killing fast-growing abnormal cells. Gemcitabine is a chemotherapy drug that blocks the cells from making DNA and may kill tumor cells. CPI-613 (devimistat) in combination with hydroxychloroquine and 5-fluorouracil or gemcitabine may work to better treat advanced solid tumors.

The presence of a BRAFV600E mutation is a marker of poor prognosis in patients with mCRC and associated with a median overall survival (mOS) of approximately 12 to 14 months compared to 20 to 25 months for patients with BRAF wild-type tumours. After 1st line therapy, treatment outcomes with standard therapy are poor in patients with BRAF-mutated mCRC, with response rates (ORR) of ≤ 11%, a median progression-free survival (mPFS) between 1.8 and 2.8 months, and a mOS between 4.1 and 6.2 months. Failure to achieve adequate survival outcomes with standard treatment regimens in patients with BRAF-mutated mCRC has encouraged efforts to combine multiple targeted therapies: With 665 randomized patients, the BEACON CRC trial represents the largest trial and is currently the only phase III study in patients with BRAFV600E-mutant mCRC. BERING CRC - designed as a prospective (allowing initial retrospective documentation), longitudinal, non-interventional study - will investigate the real-world effectiveness, quality of life, safety and tolerability of encorafenib and cetuximab in BRAFV600E-mutant mCRC patients, who have received prior systemic therapy. Data from this study will contribute to a deeper understanding and characterization to the everyday use of encorafenib and cetuximab in a broader patient population in the German, Austrian, and Swiss routine setting.