66 Clinical Trials for Various Conditions
Phase Ib dose escalation in advanced solid tumors to identify dose for Phase II dose expansion in advanced or metastatic pancreatic cancer and KRAS-mutant colorectal cancer. Open-label, nonrandomized.
The goal of this clinical research study is to learn if ivonescimab can help to control previously treated, metastatic colorectal cancer.
Background: Gastrointestinal (GI) cancer affects the organs (such as the stomach, large and small intestine, pancreas, colon, liver, and biliary system) of the digestive tract. In some participants who have had surgery for GI cancer, blood tests show that the cancer has spread despite being unable to be identified by scans. Certain gene mutations (changes) in GI cancer (such as KRAS or TP53) can be targeted by T cells, a type of immune cell, in individuals with specific HLA types (genes that help proteins in the body know what is self and non-self). Researchers want to see if they can stop GI cancer from returning or spreading in people with these gene mutations and specific HLA types. Objective: To test therapy with modified T-cells to prevent or delay the return of GI cancer after standard treatment. T-cells play a role in the body s immune system. Eligibility: People aged 18 to 72 years with GI cancer that was treated with standard therapy and is not seen on imaging scans. They must have specific gene mutations and HLA types. They also must have certain clinical or blood tests showing the cancer is spreading (elevating CA19-9 or detectable ctDNA). Design: Participants will be divided into 2 groups. Participants nor the study team can choose what Group to participate in; this is done by randomization , like flipping a coin. Participants will have a 1-to-1 chance of being in Group 1 or Group 2. Group 1 will receive T-cell therapy. Their own T-cells will be collected. In a lab, the cells will be combined with a virus that carries a protein to target cancer cells. Group 1 participants will stay in the hospital for 3 weeks or more. They will have chemotherapy, and their modified T-cells will be infused through a tube attached to a needle inserted into a vein. Group 1 participants will visit the clinic every 3 months for 1 year and then every 6 months for 5 years. Then they will have follow-up visits for another 10 years under a different protocol. Group 2 participants will not receive treatment with T-cells. They will visit the clinic every 3 months for 1 year and then every 6 months for 5 years.
Background: People with colorectal cancer (CRC) or gastroesophageal cancer (GEC) must often have major surgery to remove tumors from the esophagus, stomach, colon, or rectum. These surgeries can have adverse effects on their quality of life. Researchers want to know if one or two approved drugs (nivolumab with or without ipilimumab) can help people with CRC or GEC delay or avoid surgery. Objective: To test 1 or 2 drugs in people with CRC or GEC. Eligibility: People aged 18 years and older with CRC or GEC. People with GEC must also have changes in a particular gene. Design: Participants will visit the clinic about 15 times over the first 2 years. Each visit will last 4 to 8 hours. Participants will be screened. They will have a physical exam with blood and urine tests. They will have imaging scans. Small samples of tissue will be collected from their upper or lower digestive tract where the tumor is located. Both ipilimumab and nivolumab are administered through a tube attached to a needle inserted into a vein in the arm. Some participants will receive both drugs. Some will receive only nivolumab. Treatment will be given once every 3 weeks for up to 8 cycles up to (24 weeks). Participants will be evaluated every 6 weeks. Those who are responding well will continue with the drug treatments. If their disease progresses, they will go to surgery. After treatment ends, participants will have follow-up visits every 6 months for up to 5 years....
This randomized, phase 2 study will investigate the use of the Signatera ctDNA assay versus the standard scan-based approach to guide treatment in patients with metastatic colorectal cancer. The aim of this study will be to measure and compare the overall survival, progression-free survival, and best overall response while on study of patients whose treatment has been guided by these two approaches.
Background: Metastatic or refractory/recurrent small bowel and colorectal cancers cannot be cured and are often not helped by standard treatments. Researchers want to find better treatments by testing a combination of drugs. Objective: To learn if a new combination of immunotherapy drugs can shrink tumors in people with advanced small bowel and colorectal cancers. Eligibility: People ages 18 and older who have advanced metastatic or refractory/recurrent small bowel and/or colorectal cancer. Design: Participants will be screened on a separate protocol. They will have a physical exam and medical history. They will have imaging scans. They will have blood and urine tests. Their heart function will be measured. They may have a tumor biopsy. Participants will repeat some of the screening tests during the study. Participants will be put into study groups. Each group will get a combination of the following drugs: CV301 vaccine (modified vaccinia Ankara (MVA)-BN-CV301 and Fowlpox (FPV)-CV301), M7824 (MSB0011359C), and N-803 (Anktiva). Some will also get NHS-IL12 (M9241). Participants will get the CV301 vaccines by injection under the skin. They will get M7824 by intravenous infusion every 2 weeks. They will get N-803 by injection under the skin every 2 or 4 weeks. They may get NHS-IL12 by injection under the skin every 4 weeks. They will take the study drugs for up to 1 year. They will visit the National Institutes of Health (NIH) every 2 weeks. After treatment ends, participants will go to the clinic for a 28-day follow-up visit or have a telephone call. They will be contacted every 3 months for 1 year, and then every 6 months after that for the rest of their life.
This is a multi-site, open-label, Phase II, randomized, trial to compare the efficacy of RO7198457 versus watchful waiting in patients with circulating tumor DNA (ctDNA) positive, surgically resected Stage II/III rectal cancer, or Stage II (high risk)/Stage III colon cancer.
This randomized phase II trial studies how well irinotecan hydrochloride and cetuximab with or without vemurafenib works in treating patients with colorectal cancer that has spread to nearby tissue or lymph nodes, that has spread to other places in the body, or cannot be removed by surgery. Irinotecan hydrochloride and vemurafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as cetuximab, may block the ability of tumor cells to grow and spread. It is not yet known whether irinotecan hydrochloride and cetuximab are more effective with or without vemurafenib in treating colorectal cancer.
This is an open label, two-arm, phase II trial to evaluate the anti-tumor activity, safety, and tolerability of ziv-aflibercept in combination with XELOX chemotherapy in the first-line treatment of subjects with mCRC. Two different schedules of ziv-aflibercept in combination with XELOX will be evaluated in this study: every 2 week schedule (Arm A) and the every 3 week schedule (Arm B). The choice between arm A and arm B will depend on the investigator's preference. Arm A (every 2 week schedule) Dosage and dosage regimen for all study periods * Capecitabine: will be administered 1,000 mg/m2 orally twice a day on Days 1 - 7 of each cycle, repeating every 14 days. * Oxaliplatin: will be administered 85 mg/m2 IV on Day 1 of each cycle, repeating every 14 days. * Ziv-aflibercept: will be administered 4 mg/kg IV on Day 1 of each cycle, repeating every 14 days. Arm B (every 3 week schedule): Dosage and dosage regimen for all study periods * Capecitabine: will be administered 850 mg/m2 orally twice a day on Days 1 - 14 of each cycle, repeating every 21 days. * Oxaliplatin: will be administered 130 mg/m2 IV on Day 1 of each cycle, repeating every 21 days. * Ziv-aflibercept: will be administered 6 mg/kg IV on Day 1 of each cycle, repeating every 21 days.
The purpose of this study is to establish the safety of Zaltrap in patients who undergo pre-operative chemotherapy with Zaltrap. The investigators hypothesize that Zaltrap my impact colorectal cancer growth and metastasis.
The purpose of this study is to collect prospective data for use as a comparator for future subsequent studies attempting to increase the efficacy or reduce the toxicity of gamma knife radiosurgery.
The goal of this clinical research study is to learn if minocycline can reduce numbness, pain, and/or loss of motor function in patients with colorectal cancer. In this study, minocycline will be compared to a placebo. The study doctor can explain how the study drug is designed to work. A placebo is not a drug. It looks like the study drug, but it is not designed to treat any disease or illness. It is designed to be compared with a study drug to learn if the study drug has any real effect.
T cells can penetrate virtually every biologic space and have the power to dispose of normal or malignant cells as seen in viral and autoimmune diseases and in the rare spontaneous remis-sions of cancer. However, T cells are easily tolerized to self or tumor antigens and "immune surveillance" has manifestly failed in every cancer that is clinically apparent. It is the goal of these studies to supply the specificities and affinities to patient T cells without regard for their "endogenous" T cell receptor repertoire, directed by antibody-defined recognition to kill malignant cells based on their expression of antigen. We will achieve this by preparing chimeric IgCD28TCR genes in mammalian expression vectors to yield "designer T cells" from normal patient cells. This extends the approach of Anderson, Rosenberg and co-workers to introduce or augment expression of genes in patients' T cells in a therapeutic setting. Prior studies in model systems demonstrated that recombinant IgCD28TCR could direct modified T cells to respond to antigen targets with IL2 secretion, cellular proliferation, and cytotoxicity, the hallmarks of an effective, self-sustaining immune response. It therefore becomes of paramount interest to extend these studies to a human system of widespread clinical relevance to explore the clinical potential of this new technology. The target antigen for these studies is carcinoembryonic antigen (CEA) which is predominantly expressed on tumors of the colon and rectum, breast, pancreas and other sites.
Preliminary studies with a variety of vaccines suggest target accessibility (potential immunogenicity) in a variety of solid tumors to immune directed approaches. In an effort to overcome limitations of immunostimulatory cancer vaccines, Gradalis has designed a novel autologous vaccine to address inability to fully identify cancer associated antigens, antigen recognition by the immune system (i.e. antigen--\>immunogen), effector potency, and cancer-induced resistance. In an effort to overcome limitations of immunostimulatory cancer vaccines, we designed a novel dual-modulatory autologous whole cell vaccine, Vigil™, incorporating the rhGMCSF transgene and the bifunctional shRNAfurin (to block proprotein conversion to active TGFb1 and b2) to 1) address the inability to fully identify cancer associated antigens, 2) effect antigen recognition by the immune system, 3) enhance effector potency, and 4) subvert endogenous cancer-induced immune resistance. We have also completed the Phase I assessment of Vigil™ vaccine in 30 advanced solid tumor patients (1.0 x 10\^7 cells/injection/month for a maximum of 12 vaccinations) who have not experienced any significant adverse effects following 144 vaccinations, including 6 patients with colorectal carcinoma. Plasmid functionality, immune biomarker response, and preliminary evidence of anticancer activity have been observed. This is a two-part Phase II study of the Vigil™ autologous vaccine. Six patients will be enrolled into the Part 1 of the study to receive intradermal autologous Vigil™ cancer vaccine (1.0 x 10\^7 cells/injection; maximum of 12 vaccinations). Part 2 of the study will be a randomized Phase II study of sandwich or adjuvant chemotherapy and intradermal autologous Vigil™ cancer vaccine (1.0 x 10\^7 cells/injection; maximum of 12 vaccinations) versus sandwich or adjuvant chemotherapy and placebo in patients with colorectal carcinoma with either synchronous or metachronous liver metastases (CLM +/= pulmonary metastases) following resection +/= ablation with curative intent.Sandwich therapy indicates a combination of both pre-operative and postoperative chemotherapy as opposed to neo-adjuvant (all chemotherapy prior to surgery) or adjuvant (all chemotherapy following surgery) therapy. A minimum harvest aliquot to produce 4 monthly injections will be required for entry into the study. Patients in whom insufficient tissue (\<4 doses) is collected or whose vaccine fails manufacturing release criteria will not receive vaccine.
This randomized (2:1), multi-center, placebo-controlled, phase II efficacy study is designed to compare PFS between regorafenib + FOLFIRI chemotherapy (ARM A) versus placebo + FOLFIRI (ARM B) in patients with mCRC previously treated with a FOLFOX regimen.
Background: * The drug R935788 (fostamatanib disodium) is a kinase inhibitor (i.e., it interferes with cell communication and growth and may prevent tumor growth). * R935788 has shown promising activity in NCI-60 (a panel of 60 diverse human cancer cell lines) against colon cancer, non-small cell lung cancer, and renal cell carcinoma cell lines, as well as in two renal cell xenograft models. * This is an open-label, Phase II study of R935788. Phase I studies in patients with immune thrombocytopenic purpura, rheumatoid arthritis, and lymphoma have demonstrated safety with a continuous dosing schedule, and a maximum tolerated dose has been established. Objectives: * To test an experimental drug called R935788 (fostamatinib disodium) for its ability to stop cancer growth signals, thus slowing the growth of cancer cells in laboratory testing. * To determine the clinical response of R935788 administered orally twice a day on a continuous schedule in patients with colorectal carcinoma, pheochromocytoma, follicular or papillary thyroid cancer, non-small cell lung cancer, hepatocellular, carcinoma of the head and neck, and renal cell carcinoma. * To evaluate the effects, safety, and biochemical response of R935788 therapy. Eligibility: * Patients with colorectal carcinoma, pheochromocytoma, follicular or papillary thyroid cancer, non-small cell lung cancer (excluding squamous cell histology), hepatocellular cancer, carcinoma of the head and neck, and renal cell carcinoma whose disease has progressed after any therapy or who have no acceptable standard treatment options. * Patients must have recovered from toxicities of prior therapies to at least eligibility levels. * Patients who have received radiation or chemotherapy within 4 weeks of study enrollment are not eligible. * Women who are pregnant or breastfeeding are not eligible. Design: * Researchers will conduct the following tests and procedures during the study: * Clinic visits with a physical exam, including vital signs and blood pressure, every other week during cycle 1, and once a month starting with cycle 2. * Blood will be drawn weekly during cycle 1, every other week during cycle 2, and once a month starting with cycle 3; urine tests will be conducted depending on results of blood tests. * Imaging tests, such as computed tomography (CT) scans (a series of x-rays) or ultrasound (an examination using sound waves), will be done every 8 weeks while the patient is receiving R935788. * R935788 will be administered orally twice a day for 28 days (one cycle). Imaging studies will be obtained every two cycles. Patients will fill in a diary to show when they took the medication and to note any side effects. The 28-day treatment cycle will be repeated as long as the patient is tolerating R935788 and the cancer is either stable or getting better. * Researchers will conduct the following additional tests to see how the study is affecting the patient: * Other research blood samples will be collected before treatment, at cycle 1 week 3, at the beginning of cycle 2, and at 8 weeks. * Optional tumor biopsies will be requested before starting treatment, at cycle 1 day 28. * Patients with specific lesions or tumors may be asked for an optional tumor biopsy on day 8.
The purpose of this study is to evaluate progression free survival primarily. The secondary objectives are to evaluate the antitumor activity, as assessed by objective tumor response, duration of clinical benefit, overall survival, and the safety profile of TAS-109
The proposed plan will investigate the mechanism and efficacy of Chinese herbal medicine as an adjunct to chemotherapy in treatment of patients with metastatic colorectal cancer. Our rationale for the therapeutic use of KD018 is its potential activity in reducing chemotherapy-induced toxicity, especially diarrhea.
The purpose of this study is to determine the effects of the study drug, LBH589, on patients with metastatic colorectal cancer that has continued to grow despite previous treatment.
This is an open-label, phase II study to evaluate the efficacy and safety of Abraxane in combination with Capecitabine in patients with metastatic colorectal cancer in the second or third line
The purpose of this study is to find out how effective this combination is as a second line treatment for colorectal cancer that has spread from one part of the body to another (metastasized) or has not metastasized but is considered inoperable (unable to be removed by surgery). The side effects and survival experienced by subjects receiving these drugs will also be evaluated. This is a phase II research study.
The addition of RAD001, an mTOR inhibitor, to irinotecan and anti-EGFR antibody cetuximab may increase efficacy for patients with metastatic colorectal cancer who progressed on prior chemotherapy. This approach is biologically directed to overall target the cancer cell at multiple levels, and potentially preventing chemotherapy and EGFR-therapy resistance.
The purpose of this study is to assess the efficacy and safety of 2 doses of ZACTIMA™ (ZD6474) in combination with FOLFIRI vs FOLFIRI alone for the treatment of colorectal cancer in patients who have failed therapy with an oxaliplatin and fluoropyrimidine containing regimen.
RATIONALE: Aprepitant, palonosetron, and dexamethasone may help lessen or prevent nausea and vomiting in patients receiving chemotherapy. PURPOSE: This phase II trial is studying how well giving aprepitant together with palonosetron and dexamethasone works in preventing nausea and vomiting caused by chemotherapy in patients receiving chemotherapy for metastatic colorectal cancer.
Single center open-label study of an oral agent (RAD001) in subjects with metastatic colorectal cancer refractory to at least 2 standard chemo/biologic regimens.
Background: * Colorectal cancer (CRC) is a major public health problem in the U.S. and worldwide, and 5-year survival with widespread metastatic disease is less than 5%. * Expression of epidermal growth factor receptor (EGFR) or up-regulation of the gene occurs in the majority of CRC cases (60-80%). * Therapies targeting EGFR, like cetuximab, have shown activity in the treatment of solid tumors like CRC. * Cetuximab is FDA (Food and Drug Administration) approved for the treatment of EGFR-expressing CRC, but clinical responses to cetuximab are seen in only 10% of EGFR-expressing CRC. * One possible mechanism of resistance to cetuximab could be KRAS (Kirsten rat sarcoma) mutations. * Another major pathway implicated in colon carcinogenesis is the vascular endothelial growth factor (VEGF) pathway, which is involved in angiogenesis and is a validated target for therapy in CRC. * BAY 43-9006 is both a Raf kinase inhibitor and an inhibitor of VEGF receptor (VEGFR2) tyrosine kinase. * We hypothesize that the combined inhibition of EGFR, VEGFR2, and the Ras-(rapidly accelerated fibrosarcoma) Raf pathway will demonstrate promising clinical activity in CRC. Furthermore, in patients with mutant KRAS, combination of cetuximab with a drug that inhibits Raf kinase and acts downstream of Ras mutations, could restore tumor sensitivity to cetuximab. Objectives: * To determine the rate of response (complete response (CR) + partial response (PR) + stable disease (SD) for 4 months) and toxicity profile of combination of BAY 43-9006 and cetuximab in previously treated EGFR-expressing metastatic CRC in patients with mutant KRAS. * To evaluate BAY 43-9006 pharmacokinetics \& pharmacogenomics (CYP3A4/5 (cytochrome P450 3A4/5)). * To evaluate for this combination treatment pharmacodynamics, effect on tumor vascularity and effect on angiogenic cytokines. Eligibility: * Adults with histologically or cytologically documented, measurable, EGFR-expressing metastatic CRC, which has recurred or progressed following at least one prior 5FU (Fluorouracil)-based combination chemotherapy regimen administered for the treatment of metastatic disease. * Patients must be KRAS mutation-positive. Design: * BAY 43-9006 will be administered 400 mg by mouth twice daily * Cetuximab will be administered as 400 mg/m\^2 loading dose (week 1) followed by 250 mg/m\^2 IV (intravenous) weekly. * If procedure may be performed safely, tumor biopsy will be obtained prior to treatment and after 4 weeks of treatment. * Optional positron emission tomography (PET)/computerized tomography (CT) imaging with 89Zr-labeled, EGFR-targeting antibody panitumumab may be performed to evaluate radiation dosimetry, safety, and tumor distribution prior to and following treatment with study agents. * Patients will be evaluated for response every 8 weeks using the RECIST (Response Evaluation Criteria in Solid Tumors) criteria. * This trial uses a phase II optimal design targeting a response rate as defined above of 20% in patients with mutant KRAS. Up to 49 patients may be treated.
This study proposes to determine the safety of the administration of E7820 plus cetuximab and explore the MTD of the combination in a Phase Ib study. In addition, the efficacy of this combination will be explored in patients with colorectal cancer in the Phase II proof of concept phase of the study.
This is a Phase II, open label, non-randomized study in patients with histologically or pathologically confirmed diagnosis of stage IIIB/IV, EGFR+ adenocarcinoma of the colon or rectum who have not received prior chemotherapy for their metastatic disease. Primary Study Endpoint: To assess the response rate, progression-free survival, and overall safety profile of a modified FOLFOX 6 plus cetuximab regimen in the first-line treatment of patients with metastatic colorectal cancer. Secondary Study Endpoint(s): To assess overall survival of patients with metastatic colorectal cancer who receive first-line therapy with a modified FOLFOX 6 + cetuximab regimen.
Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab and cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of colorectal cancer by blocking blood flow to the tumor. Giving combination chemotherapy together with bevacizumab and cetuximab may kill more tumor cells. This phase II trial is studying how well giving combination chemotherapy together with bevacizumab and cetuximab works in treating patients with stage IV colorectal cancer that cannot be removed by surgery.
Positron Emission Tomography (PET scanning) is performed using a total dose of less than 50 mRad per patient visit. Fludeoxyglucose F 18 (FDG) is injected intravenously over 2 min. Initial dynamic images will be obtained over the heart. Emission imaging will work from the midcervical region down to the perineal region. For CEA scanning, radiolabeled antibody, arcitumomab (IMMU-4), is injected intravenously over 5 min. A single photon emission computed tomography (SPECT) transmission scan is performed over the same regions as the emission scans. Total dose from transmission scans should be no more than 20 mRad per patient visit. Patients then undergo exploratory laparotomy performed by two surgeons, one blinded to the results of the CEA-Scan and PET scan. At the completion of all exploration, all identified disease is biopsied for pathologic analysis and any resectable disease is removed. Patients are followed every 3 months for 1 year, every 6 months for the second year, and then after 3 years.