Dataset Information

Neo-adjuvant chemotherapy followed by surgery versus surgery alone in high-risk patients with resectable colorectal liver metastases: the CHARISMA randomized multicenter clinical trial.

ABSTRACT:

Background

Efforts to improve the outcome of liver surgery by combining curative resection with chemotherapy have failed to demonstrate definite overall survival benefit. This may partly be due to the fact that these studies often involve strict inclusion criteria. Consequently, patients with a high risk profile as characterized by Fong's Clinical Risk Score (CRS) are often underrepresented in these studies. Conceptually, this group of patients might benefit the most from chemotherapy. The present study evaluates the impact of neo-adjuvant chemotherapy in high-risk patients with primary resectable colorectal liver metastases, without extrahepatic disease. Our hypothesis is that adding neo-adjuvant chemotherapy to surgery will provide an improvement in overall survival (OS) in patients with a high-risk profile.

Methods/design

CHARISMA is a multicenter, randomized, phase III clinical trial. Patients will be randomized to either surgery alone (standard treatment, arm A) or to 6 cycles of neo-adjuvant oxaliplatin-based chemotherapy, followed by surgery (arm B). Patients must be ≥ 18 years of age with liver metastases of histologically confirmed primary colorectal carcinoma. Patients with extrahepatic metastases are excluded. Liver metastases must be deemed primarily resectable. Only patients with a CRS of 3-5 are eligible. The primary study endpoint is OS. Secondary endpoints are progression free survival (PFS), quality of life, morbidity of resection, treatment response on neo-adjuvant chemotherapy, and whether CEA levels can predict treatment response.

Discussion

CHARISMA is a multicenter, randomized, phase III clinical trial that will provide an answer to the question if adding neo-adjuvant chemotherapy to surgery will improve OS in a well-defined high-risk patient group with colorectal liver metastases.

Trial registration

The CHARISMA is registered at European Union Clinical Trials Register (EudraCT), number: 2013-004952-39 , and in the "Netherlands national Trial Register (NTR), number: 4893.

SUBMITTER: Ayez N

PROVIDER: S-EPMC4377036 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Publications

Neo-adjuvant chemotherapy followed by surgery versus surgery alone in high-risk patients with resectable colorectal liver metastases: the CHARISMA randomized multicenter clinical trial.

Ayez Ninos N van der Stok Eric P EP de Wilt Hans H Radema Sandra A SA van Hillegersberg Richard R Roumen Rudi M RM Vreugdenhil Gerard G Tanis Pieter J PJ Punt Cornelis J CJ Dejong Cornelis H CH Jansen Rob L RL Verheul Henk M HM de Jong Koert P KP Hospers Geke A GA Klaase Joost M JM Legdeur Marie-Cecile MC van Meerten Esther E Eskens Ferry A FA van der Meer Nelly N van der Holt Bruno B Verhoef Cornelis C Grünhagen Dirk J DJ

BMC cancer 20150326

<h4>Background</h4>Efforts to improve the outcome of liver surgery by combining curative resection with chemotherapy have failed to demonstrate definite overall survival benefit. This may partly be due to the fact that these studies often involve strict inclusion criteria. Consequently, patients with a high risk profile as characterized by Fong's Clinical Risk Score (CRS) are often underrepresented in these studies. Conceptually, this group of patients might benefit the most from chemotherapy. T ...[more]

PMID: 25884448

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Project description:BackgroundImprovement in treatment for patients with recurrent ovarian cancer is needed. Standard therapy in patients with platinum-sensitive recurrent ovarian cancer consists of platinum-based chemotherapy. Median overall survival is reported between 18 and 35 months. Currently, the role of surgery in recurrent ovarian cancer is not clear. In selective patients a survival benefit up to 62 months is reported for patients undergoing complete secondary cytoreductive surgery. Whether cytoreductive surgery in recurrent platinum-sensitive ovarian cancer is beneficial remains questionable due to the lack of level I-II evidence.Methods/designMulticentre randomized controlled trial, including all nine gynecologic oncologic centres in the Netherlands and their affiliated hospitals. Eligible patients are women, with first recurrence of FIGO stage Ic-IV platinum-sensitive epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer, who meet the inclusion criteria. Participants are randomized between the standard treatment consisting of at least six cycles of intravenous platinum based chemotherapy and the experimental treatment which consists of secondary cytoreductive surgery followed by at least six cycles of intravenous platinum based chemotherapy. Primary outcome measure is progression free survival. In total 230 patients will be randomized. Data will be analysed according to intention to treat.DiscussionWhere the role of cytoreductive surgery is widely accepted in the initial treatment of ovarian cancer, its value in recurrent platinum-sensitive epithelial ovarian cancer has not been established so far. A better understanding of the benefits and patients selection criteria for secondary cytoreductive surgery has to be obtained. Therefore the 4th ovarian cancer consensus conference in 2010 stated that randomized controlled phase 3 trials evaluating the role of surgery in platinum-sensitive recurrent epithelial ovarian cancer are urgently needed. We present a recently started multicentre randomized controlled trial that will investigate the role of secondary cytoreductive surgery followed by chemotherapy will improve progression free survival in selected patients with first recurrence of platinum-sensitive epithelial ovarian cancer.

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Dataset Information

Neo-adjuvant chemotherapy followed by surgery versus surgery alone in high-risk patients with resectable colorectal liver metastases: the CHARISMA randomized multicenter clinical trial.

Background

Methods/design

Discussion

Trial registration

Publications

Neo-adjuvant chemotherapy followed by surgery versus surgery alone in high-risk patients with resectable colorectal liver metastases: the CHARISMA randomized multicenter clinical trial.

Similar Datasets

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