View clinical trials related to Metastatic Colorectal Cancer.
Filter by:The purpose of the study is to evaluate if the exposure to all the three active cytotoxic agents (FOLFOXIRI regimen) is superior in terms of progression-free survival to conventional chemotherapy with the FOLFOX regimen as first-line treatment of chemo-naive metastatic colorectal cancer patients. A second primary aim is to evaluate the response rate, safety and tolerability of the chemotherapy of FOLFOXIRI regimen in this patient population. Patients will be randomized to two therapy groups: Experimental arm A: Chemotherapy with FOLFOXIRI Standard arm B: Chemotherapy with FOLFOX
Since its introduction, 5-fluorouracil (5-FU) has been the cornerstone of treatment for metastatic colorectal cancer (mCRC). Meanwhile the oral 5FU pro-drug Capecitabine (Xeloda®) proved equivalence to 5-FU and is a well tolerated alternative combination partner for Irinotecan (XELIRI) or Oxaliplatin (XELOX) which are widely used for first line treatment of mCRC. Recent advances in molecular biology have resulted in the development of an inhibitor of the vascular endothelial growth factor (VEGF) by the monoclonal humanized antibody bevacizumab (Avastin®). XELOX or XELIRI +bevacizumab have been investigated in several trials, but not in an approach with clearly defined cross-wise XELIRI-XELOX change criteria. This trial investigates two different sequential treatment options with XELIRI/ XELOX in first and second line with the addition of bevacizumab and tries to give answer to the question if there is an optimal sequence for the benefit of the patient. This is a prospective, randomized, open-label, 2-arm pilot trial in patients with mCRC who did not receive systemic treatment for their metastatic disease. The study is designed to evaluate the efficacy of XELIRI followed by XELOX and XELOX followed by XELIRI + bevacizumab in terms of Duration of Disease Control (DDC). Patients will be treated with an established first line therapy consisting of either XELOX or XELIRI + bevacizumab. The chemotherapy treatment will be given for 6 months except prior disease progression, unacceptable toxicity or patient refusal. Bevacizumab will be given until disease progression, unacceptable toxicity or patient refusal. Capecitabine can be given in addition at the investigators' discretion until disease progression, unacceptable toxicity or patient refusal. If serious side effects occur despite adequate dose reduction, Oxaliplatin or Irinotecan should be discontinued. In case of Oxaliplatin or Irinotecan-related discontinuation Capecitabine and Bevacizumab should be continued. If Capecitabine also has to be discontinued in first line treatment bevacizumab should be continued. In case of permanent discontinuation of bevacizumab for toxicities, chemotherapy should be continued. Upon completion of first line chemotherapy patients with disease control will receive bevacizumab maintenance treatment. On investigators decision patients can receive Capecitabine as additional maintenance treatment. The primary endpoint is to determine the efficacy of a modified XELIRI + bevacizumab followed by XELOX + bevacizumab scheme at progression in comparison with the reverse sequence based on DDC. Secondary endpoints are first line progression-free survival (PFS), second line PFS, overall response rate, time to response, duration of response, overall survival, tumor assessments (based on RECIST criteria) using CT scans, MRI scans, X-ray, bone scan, clinical examination.
In this study the investigators will evaluate the uptake of 89Zirconium labeled cetuximab in extra-hepatic colorectal metastases. The investigators hypothesize that uptake of 89Zr-cetuximab is required for response to cetuximab. If no uptake is present the investigators will escalate the dose cetuximab and repeat the 89Zr-cetuximab PET. The investigators will evaluate the clinical benefit rate of cetuximab in the patients with and without uptake. The ultimate goal is to create a selection tool that can predict response of cetuximab.
The primary objective of this study is to determine whether systemic chemotherapy combined with hepatic arterial infusion with floxuridine and dexamethasone can increase the complete resection rate (R0) and improve the overall survival in patients with initially unresectable colorectal liver metastasis.
The metastatic colon cancer is a major public health problem despite advances in chemotherapy; few new drugs are in development for the treatment of this pathology. Many studies have shown that human colon cancer is a tumor that is recognized by the immune system and the presence of lymphocytic infiltrates in the tumor bed is associated with a better prognosis. Conversely, the effect of chemotherapy on the immune response is little studied. Recently the importance of myeloid suppressor cells (MDSC) in the development of colon cancer and the effect of 5- fluorouracil on this cell population has been highlighted. An accumulation of these cells in the blood and lymphoid organs during tumor progression is observed. Moreover, it has been established that the death of MDSC induced by 5-fluorouracil induces activation of caspase -1 and IL-1beta by these MDSC. These events promote the polarization of CD4 T cells in intratumoral Th17 lymphocytes. The IL- 17 produced by these cells exerts a pro-angiogenic effect in inducing proliferation of endothelial cells expressing and thus limits the effect of 5- fluorouracil endoglin. In humans, it has also been observed that chemotherapy using 5- fluorouracil and in particular LV5FU2 association +/- bevacizumab induces rapid death of blood MDSC as well as activation of caspase 1 in these cells. Thus, production of IL - 1 is detected in the serum of patients after 24 hours of the administration of 5-fluorouracil. Chronic inflammation and the production of interleukin- 1 can alter the effectiveness of anti -tumor immune responses and facilitate angiogenesis. Many preclinical data suggest a role of anti -tumor inhibition of IL- 1beta, but the effect of a combination of chemotherapy and an inhibitor of IL - 1beta has not yet been tested in human. Anakinra is a drug used in humans for many years to treat signs and symptoms of rheumatoid arthritis. In combination with methotrexate, in patients whose response to methotrexate alone is not satisfactory it had shown interesting results. The dose used clinically is 100 mg per day which is the dose that is proposed to be tested in this study. In this context it should be remembered that methotrexate is a chemotherapeutic agent from the class of antimetabolites such as 5- fluorouracil. RCP of this drug indicate that in studies originator toxicity was similar between the control arm and anakinra arm with an increase in serious infections (1.8 % vs 0.7 %) and an increased incidence of neutropenia (2.5 % neutropenia > grade = 1). The main toxicity observed is a painful inflammatory reaction at the injection site in 70 % of patients The investigators believe that this project could permit to validate in man preclinical observations showing an anti-tumor potential for combination anakinra and 5 fluorouracil.
This is a Phase 2, open-label, randomized, 3-arm trial investigating the efficacy of two Sym004 doses (Arm A and Arm B) compared with a control group (Arm C) in subjects with metastatic colorectal cancer (mCRC) and acquired resistance to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs).
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 this trial is to prove the efficacy and safety of MGN1703 as a maintenance therapy after first-line chemotherapeutic treatment of metastatic colorectal cancer.
The purpose of this study is to evaluate the efficacy and safety of recombinant anti-tumor and anti-virus protein for injection plus capecitabine in treating patients with metastatic colorectal cancer who have progressed after standard therapy.
PURPOSE: A primary aim of phase II FOCULM study is to explore whether cetuximab in combination with FOLFOXIRI as first treatment could improve surgical conversion in patients with KRAS/NRAS wild-type, unresectable liver - only metastases of colorectal cancer. The first secondary aim is to evaluate the safety and tolerability of the chemotherapy of FOLFOXIRI plus Cetuximab targeted therapy regimen in this patient population. Secondary aims include determination of objective response rate, progression free survival, quality of life and time to recurrence for patients undergoing complete resection and/or ablation of liver.