Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.
Trial record 23 of 146 for:    colon cancer AND Capecitabine

Proactive Management of Endoperitoneal Spread in Colonic Cancer (PROMENADE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02974556
Recruitment Status : Not yet recruiting
First Posted : November 28, 2016
Last Update Posted : November 9, 2018
Sponsor:
Information provided by (Responsible Party):
Paolo Sammartino, University of Roma La Sapienza

Tracking Information
First Submitted Date  ICMJE November 9, 2016
First Posted Date  ICMJE November 28, 2016
Last Update Posted Date November 9, 2018
Estimated Study Start Date  ICMJE March 1, 2019
Estimated Primary Completion Date September 1, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 22, 2016)
Incidence of endoperitoneal recurrence at 36 months [ Time Frame: 36 months ]
The primary endpoint is the incidence of endoperitoneal recurrence at 36 months defined as the proportion of subjects with peritoneal metastases at 36 months from randomization.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02974556 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 22, 2016)
  • disease-free survival (DFS) [ Time Frame: 3 years ]
  • disease-free survival (DFS) [ Time Frame: 5 years ]
  • overall survival (OS) [ Time Frame: 3 years ]
  • overall survival (OS) [ Time Frame: 5 years ]
  • extraperitoneal (systemic) or liver recurrence rate [ Time Frame: 3 years ]
  • morbidity rate [ Time Frame: 1 month ]
  • morbidity rate [ Time Frame: 6 months ]
  • HIPEC toxicity rate [ Time Frame: 1 month ]
  • HIPEC toxicity rate [ Time Frame: 6 month ]
  • EORTC QLQ-C30 Summary Score [ Time Frame: 6 months ]
    The EORTC QLQ-C30 Summary Score range from 0 to 100 and is calculated from the mean of 13 of the 15 QLQ-C30 scales (the Global Quality of Life scale and the Financial Impact scale are not included). Prior to calculating the mean, the symptom scales need to be reversed to obtain a uniform direction of all scales. QLQ-C30 Summary Score = (Physical Functioning+ Role Functioning+ Social Functioning+ Emotional Functioning+ Cognitive Functioning+ 100-Fatigue+ 100-Pain+ 100-Nausea_Vomiting+ 100-Dyspnoea+ 100-Sleeping Disturbances+ 100-Appetite Loss+ 100-Constipation+ 100-Diarrhoea)/13
  • EORTC QLQ-C30 Summary Score [ Time Frame: 1 year ]
    The EORTC QLQ-C30 Summary Score range from 0 to 100 and is calculated from the mean of 13 of the 15 QLQ-C30 scales (the Global Quality of Life scale and the Financial Impact scale are not included). Prior to calculating the mean, the symptom scales need to be reversed to obtain a uniform direction of all scales. QLQ-C30 Summary Score = (Physical Functioning+ Role Functioning+ Social Functioning+ Emotional Functioning+ Cognitive Functioning+ 100-Fatigue+ 100-Pain+ 100-Nausea_Vomiting+ 100-Dyspnoea+ 100-Sleeping Disturbances+ 100-Appetite Loss+ 100-Constipation+ 100-Diarrhoea)/13
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Proactive Management of Endoperitoneal Spread in Colonic Cancer
Official Title  ICMJE Proactive Management of Endoperitoneal Spread in Colonic Cancer
Brief Summary

This study aims to determine the oncological effectiveness, compared to standard surgical treatment, of proactive management including target organs for peritoneal spread resection (omentectomy, bilateral adnexectomy, appendectomy, hepatic round ligament resection) and preventive HIPEC (intraperitoneal oxaliplatin with concomitant i.v. 5-fluorouracil/leucovorin) following a curative resection of high-risk ( >/= 5 mm tumor invasion beyond the muscularis propria) T3 and T4 colon cancer in preventing the development of peritoneal metastases. Adjuvant systemic chemotherapy will be reserved in both groups for patients with poor prognostic factors according to Folinic acid/Fluorouracil/Oxaliplatin (FOLFOX) or to Capecitabine/Oxaliplatin (CAPOX) regimens.

Hypothesis:

The hypothesis is that compared to the standard treatment proactive management following curative resection of high-risk T3 and T4 colon cancer will reduce the development of endoperitoneal metastases

Detailed Description Colorectal cancer is one of the leading causes of cancer death in developed countries. Despite recent advances in understanding the molecular pathogenesis and improvements in diagnosis and treatment, more than 1,2 million new cases and 600,000 deaths occur annually worldwide and cure rates remain low for patients with metastatic or recurrent disease. According to reports from the National Cancer Institute, cancer of the colon is a highly treatable and often curable disease when confined to the bowel. Surgery is the primary treatment and results in a cure rate of approximately 50% of the patients; however, recurrence following surgery is a major problem and is often the ultimate cause of death. In colon cancer locoregional recurrence (local recurrence and metachronous peritoneal spread), as the main site of recurrence, is less common (up to 10% of all recurrences) and generally occurs within 3 years of resection. An important concept is the origin of local recurrences and peritoneal metastases that have a common natural history. Specific features of the primary tumor like size and depth of bowel wall invasion (pT3-pT4), which determine a specific clinical evolution (obstruction, perforation with exfoliation of cancer cells) are responsible for endoperitoneal recurrence. Cytoreductive Surgery (CRS) defined as removal of macroscopic abdominal and peritoneal disease combined with Hyperthermic Perioperative Chemotherapy (HIPEC) is the treatment considered standard of care for selected patients with moderate to small volume peritoneal metastases secondary to colorectal cancer. Nevertheless treatment of locoregional recurrence and peritoneal metastases in colon cancer are disappointing first because only 30% of patients can be surgically treated and second because of this 30% only 15- 30% survive 5 years, leaving only 10% of patients with a chance of being cured. Furthermore the economic burden of metastatic colorectal cancer treatment is considerable including the common adverse events associated that increase healthcare resource utilization and considering the addition of biological drugs to standard treatment. An evaluation of CRS combined with HIPEC for peritoneal metastases of colorectal origin in the era of value-based medicine, showed an incremental cost respect to modern chemotherapy regimens of 44,217 US$ for life-year saved, making investment in prevention even more attractive. Despite screening for colorectal cancer in average-risk patients using colonoscopy was associated with a substantially reduced risk of diagnosis with new-onset primary late-stage tumors, colorectal cancer screening remains underused. Analyzing the recent surgical published series, the majority (around 70%), of patients with a diagnosis of colonic cancer operated with curative intent, have a pT3-4 tumor, which is exactly the high-risk class of patients for local recurrence and peritoneal metastases. In this scenario the most effective strategy to combat endoperitoneal recurrence seems prevention. Two previous studies performed in our Institution investigated how a proactive management of peritoneal metastases in colon cancer patients considered at high-risk for peritoneal recurrence according to depth of bowel wall invasion and specific histopathologic features (pT3, pT4 any N, M0, mucinous or signet ring cell pathology) influence outcome. A group of 25 patients for whom inclusion criteria were verified by intraoperative pathologic assessment, were submitted to a "proactive" treatment that included in addition to the standard surgical treatment, a greater omentectomy, appendectomy, exeresis of the liver round ligament and, in post-menopausal women, a bilateral oophorectomy. At the end of the operation, in these patients a HIPEC was performed with oxaliplatin and simultaneous iv infusion of 5-fluorouracil (FU) + leucovorin (LV). Short and long-term results showed that when compared to a control group (50 cases) of similar patients treated only by standard treatment in the same Institution, this group of patients had a statistically significant decreased incidence of peritoneal recurrence (4 vs. 28%) and an increase in overall and disease-free survival rates. These results should obviously validated by larger controlled studies, and this is the aim of the PROMENADE protocol, to verify if the treatment criteria applied in colorectal peritoneal metastases (Surgery combined with HIPEC) could represent a mean of tertiary prevention of endoperitoneal recurrence in high-risk colon cancer. However, simpler application criteria were needed for a large-scale study. For this reason histological typing have not been yet considered an inclusion criteria and will only represent a secondary outcome measure. Furthermore, also considering other experiences, the protocol will use an imaging technique (MDCT) for preoperative selection of high-risk T3 (>/= 5 mm tumor invasion beyond the muscularis propria) and T4 colon cancers, combined in patients with suspected systemic disease after MDCT with functional positron-emission tomography (PET), avoiding the need for an intraoperative frozen-sections pathologic assessment. The results of this study will hopefully confirm the therapeutic rationale that makes microscopic local seeding as the main reason for endoperitoneal recurrence. It will be also important to verify if, as demonstrated in our pilot study, a better loco-regional control of the disease will carry better long-term survival.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE
  • Colon Cancer
  • Intraperitoneal Rectal Cancer
Intervention  ICMJE
  • Procedure: Standard surgical treatment
    Standard surgical treatment (open or laparoscopic techniques) containing at least 12 lymph-nodes for accurate pN staging.
  • Procedure: Proactive management
    Colon cancer patients (high-risk T3 and T4) without peritoneal or systemic metastases are resected for cure. Simultaneously patients will undergo infracolic omentectomy, appendectomy, exeresis of the liver round ligament and, in women, a bilateral oophorectomy. After positioning three in- and outflow catheters HIPEC perfusion starts with a minimum of 2 L isotonic dialysis fluid at a flow-rate of 1-2 l min and an inflow temperature of 42-43° C with a total of 30 minutes perfusion time. Before the beginning of HIPEC 5-fluouracil and leucovorin will be administrated intravenously to potentiate oxaliplatin activity.
  • Drug: Standard adjuvant systemic chemotherapy
    Adjuvant systemic chemotherapy (according CAPOX or FOLFOX regimens for a total of 6 months) will be reserved in patients with pT3 tumors with poor prognostic factors, in patients with pT4 tumors and when lymph-nodes metastases are present. Presence or absence of peritoneal recurrence will be evaluated by MDCT every six months for the first 24 months and later every year for the next three years in both study arms.
    Other Names:
    • adjuvant capecitabine and oxaliplatin (CAPOX)
    • adjuvant 5-FU and oxaliplatin (FOLFOX)
Study Arms  ICMJE
  • Active Comparator: Standard surgical treatment group

    Colon cancer patients (high-risk T3 and T4) without peritoneal or systemic metastases are resected for cure.

    Standard adjuvant systemic chemotherapy (FOLFOX or CAPOX regimens for 6 months) will be reserved in pT3 tumors with poor prognostic factors, pT4 tumor and if lymph-nodes metastases are present. Presence or absence of peritoneal recurrence will be evaluated by MDCT.

    Interventions:
    • Procedure: Standard surgical treatment
    • Drug: Standard adjuvant systemic chemotherapy
  • Experimental: Proactive management group

    Colon cancer patients (high-risk T3 and T4) without peritoneal or systemic metastases are resected for cure. Simultaneously patients will undergo infracolic omentectomy, appendectomy, exeresis of the liver round ligament and, in women, a bilateral oophorectomy. At the end of surgical procedure HIPEC will be performed with oxaliplatin 460 mg/m2 and before the beginning of HIPEC an intravenous infusion of 400 mg/m2 of 5-FU and 20 mg/m2 of leucovorin will be administered.

    Standard adjuvant systemic chemotherapy (FOLFOX or CAPOX regimens for 6 months) will be reserved in pT3 tumors with poor prognostic factors, pT4 tumor and if lymph-nodes metastases are present. Presence or absence of peritoneal recurrence will be evaluated by MDCT.

    Interventions:
    • Procedure: Proactive management
    • Drug: Standard adjuvant systemic chemotherapy
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: November 22, 2016)
140
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2025
Estimated Primary Completion Date September 1, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients with colon cancer or intraperitoneal rectosigmoid cancer with clinical (by CT) high-risk(> 5mm) T3, T4 tumors, any N, M0
  • Performance Status (ECOG) 0, 1 or 2
  • Signed informed consent

Exclusion Criteria:

  • BMI> 30
  • Impossibility of an adequate follow-up
  • Intra and extraabdominal metastatic disease, multiple colorectal cancer or other malignancies
  • Active infections or severe associated medical conditions (ASA IV or V)
  • Abnormal bone marrow or renal and liver function indices
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Paolo Sammartino, MD PhD 336615632 ext +39 paolo.sammartino@uniroma1.it
Contact: Tommaso Cornali, MD 3489012376 ext +39 tommaso.cornali@uniroma1.it
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02974556
Other Study ID Numbers  ICMJE PROMENADE v1.0
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Paolo Sammartino, University of Roma La Sapienza
Study Sponsor  ICMJE University of Roma La Sapienza
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Paolo Sammartino, MD PhD University of Roma La Sapienza
PRS Account University of Roma La Sapienza
Verification Date November 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP