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出境医 / 临床实验 / FOLFOXIRI With or Without Intensification for Rectal Cancer

FOLFOXIRI With or Without Intensification for Rectal Cancer

Study Description
Brief Summary:
Pathologic complete response rate

Condition or disease Intervention/treatment Phase
Rectal Cancer Drug: Control arm Drug: Experimental arm Phase 2

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 72 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Study of Neoadjuvant Chemoradiotherapy With or Without Intensification With the FOLFOXIRI Chemo-regimen for High-risk Locally Advanced Rectal Cancer
Actual Study Start Date : September 10, 2019
Estimated Primary Completion Date : March 31, 2022
Estimated Study Completion Date : March 31, 2023
Arms and Interventions
Arm Intervention/treatment
Experimental: Control arm
neoadjuvant concurrent capecitabine-radiotherapy followed by surgery and postoperative chemotherapy
Drug: Control arm
neoadjuvant concurrent capecitabine-radiotherapy followed by surgery and postoperative chemotherapy.

Experimental: Experimental arm
Neoadjuvant FOLFOXIRI x4 cycles, then capecitabine-radiotherapy and postoperative chemotherapy
Drug: Experimental arm
Neoadjuvant FOLFOXIRI x4 cycles, then capecitabine-radiotherapy and postoperative chemotherapy.

Outcome Measures
Primary Outcome Measures :
  1. Rate of pathologic complete response [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. Rate of tumour regression grade [ Time Frame: 2 years ]
  2. Number of objective tumour response [ Time Frame: 2 years ]
  3. Rate of circumferential resection margin (CRM) clearance [ Time Frame: 2 years ]
  4. Rate of tumour downstaging [ Time Frame: 2 years ]
  5. Number of Participants with Adverse Events [ Time Frame: 2 years ]
  6. Rate of overall survival [ Time Frame: 5 years ]
  7. Rate of disease-free survival, relapse-free survival [ Time Frame: 5 years ]
  8. Time to local (and distant) recurrence [ Time Frame: 5 years ]
  9. Number of patients with 30-days post-operative mortality [ Time Frame: 1 month ]
  10. Rate of compliance to study treatment [ Time Frame: 2 years ]
  11. Number of response to neoadjuvant therapy [ Time Frame: 2 years ]

Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Able to provide written informed consent
  • Age >= 18 years of either sex.
  • ECOG performance status 0-1
  • Measurable disease by RECIST 1.1 criteria.
  • Histologically confirmed rectal adenocarcinoma (defined as either mid- or low rectal cancer that is located within 12 cm from the anal verge OR below the peritoneal reflection) that is previously untreated.
  • 'High risk' rectal cancer, or rectal cancers that are considered marginally perable where there is a significant risk of positive surgical margin:
  • T3 or T4, and / or
  • Tumour infiltrating perirectal fat and/ or mesorectal fascia, and / or Involvement of pelvic lymph nodes, and/or
  • Tumour invading surrounding structures or peritoneum or vasculature.
  • Adequate bone marrow, renal and hepatic function as defined by: absolute neutrophil count >= 1.5 x 109/L, hemoglobin >= 9 g/L, platelets >= 100 x 109/L, serum creatinine level < 1.5 x ULN (or calculated creatinine clearance >=50 ml/min, whichever is worse), total bilirubin <=1.5 x the upper limit of normal, alanine aminotransferase (ALT) < 3 upper limit of normal.

Exclusion Criteria:

  • Known distant metastasis, even if the metastasis has been resected.
  • History of another invasive malignancy within the last 5 years, except for treated basal cell carcinoma of the skin, cervical intraepithelial neoplasia, or breast DCIS.
  • Upper rectal cancer that is located above the peritoneal reflection.
  • Patients with synchronous colon and rectal cancers are not excluded as long as: (1) these tumors are considered as two separate primaries (i.e. not metastasis or a contiguous part of a large primary), (2) both tumors are not causing imminent obstruction; (3) pelvic radiotherapy is not considered a contraindication.
  • Primary tumour associated with any one of the following features:Frank intestinal obstruction, or
  • Endoscope unable to pass through the tumour's lumen plus worsening local obstructive symptoms. Note: Patients with such features should be assessed by the surgical team regarding stomal bypass prior to study enrolment. Such patients can still be considered for study enrolment after undergoing stomal bypass.
  • Known hypersensitivity reaction to the study drugs (i.e. fluoropyrimidine, irinotecan, oxaliplatin)
  • Known peripheral neuropathy of grade 2 or more in severity.\ -Patients who have received an experimental anticancer therapy within the last 28 days.
  • Previous pelvic radiotherapy
  • Previous oxaliplatin or irinotecan for the treatment of colon or rectal cancer.
  • Patient with hip prosthesis
  • Major surgery (i.e. requiring general anaesthetics) within the last 28 days. Exception: Any patient who underwent stomal bypass for obstructing primary tumour within the last 14 days are still eligible, as long as the patient has sufficiently recovered from the surgery at the investigator's discretion.
  • Known cardiac disease that is symptomatic or poorly controlled, including cardiac failure, arrhythmia or ischemic heart disease.
  • Myocardial infarction or cerebrovascular accident within the last 12 months.
  • Intercurrent infections or medical illnesses that are serious/ potentially life-threatening and require ongoing treatment.
  • Patients who are unable to take capecitabine tablets uncrushed by the oral route (e.g. enteral feeding). Patients with significantly impaired gastrointestinal integrity and absorption are excluded.
  • Patients with known and untreated bilateral hydronephrosis and/or hydroureters (or unilateral hydronephrosis and/or hydroureters in any patient with a single kidney) are excluded. The obstruction should be treated with ureteric stent(s) or percutaneous nephrostomy(s) prior to study enrolment. Patients with unilateral hydronephrosis and/or hydroureters and adequate renal function (i.e. as stated in the eligibility criteria: serum creatinine level < 1.5 x ULN, or calculated creatinine clearance >=50 ml/min - whichever is worse) are not excluded.
  • Patients on warfarin therapy. Patients on low molecular weight heparin are not excluded.
  • Pregnant or lactating women.
  • Patients with reproductive potential who are not willing to use barrier method of birth control.
  • Patients who are unable to provide written informed consent, or to comply with study requirements as judged by the investigator.
  • Patients who refuse surgical treatment of the rectal cancer.
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Brigette MA, MD 35052118 brigette@clo.cuhk.edu.hk
Contact: Jane Koh, RN 35051142 jane@clo.cuhk.edu.hk

Locations
Layout table for location information
Hong Kong
The Chinese University of Hong Kong Recruiting
Hong Kong, Hong Kong
Contact: Brigette Ma, MD    3505 2118    brigette@clo.cuhk.edu.hk   
Contact: Jane Koh, RN    35051142    jane@clo.cuhk.edu.hk   
Sponsors and Collaborators
CCTU
Tracking Information
First Submitted Date  ICMJE June 19, 2019
First Posted Date  ICMJE June 25, 2019
Last Update Posted Date October 22, 2020
Actual Study Start Date  ICMJE September 10, 2019
Estimated Primary Completion Date March 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 23, 2019)
Rate of pathologic complete response [ Time Frame: 2 years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 23, 2019)
  • Rate of tumour regression grade [ Time Frame: 2 years ]
  • Number of objective tumour response [ Time Frame: 2 years ]
  • Rate of circumferential resection margin (CRM) clearance [ Time Frame: 2 years ]
  • Rate of tumour downstaging [ Time Frame: 2 years ]
  • Number of Participants with Adverse Events [ Time Frame: 2 years ]
  • Rate of overall survival [ Time Frame: 5 years ]
  • Rate of disease-free survival, relapse-free survival [ Time Frame: 5 years ]
  • Time to local (and distant) recurrence [ Time Frame: 5 years ]
  • Number of patients with 30-days post-operative mortality [ Time Frame: 1 month ]
  • Rate of compliance to study treatment [ Time Frame: 2 years ]
  • Number of response to neoadjuvant therapy [ Time Frame: 2 years ]
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 FOLFOXIRI With or Without Intensification for Rectal Cancer
Official Title  ICMJE A Randomized Study of Neoadjuvant Chemoradiotherapy With or Without Intensification With the FOLFOXIRI Chemo-regimen for High-risk Locally Advanced Rectal Cancer
Brief Summary Pathologic complete response rate
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Rectal Cancer
Intervention  ICMJE
  • Drug: Control arm
    neoadjuvant concurrent capecitabine-radiotherapy followed by surgery and postoperative chemotherapy.
  • Drug: Experimental arm
    Neoadjuvant FOLFOXIRI x4 cycles, then capecitabine-radiotherapy and postoperative chemotherapy.
Study Arms  ICMJE
  • Experimental: Control arm
    neoadjuvant concurrent capecitabine-radiotherapy followed by surgery and postoperative chemotherapy
    Intervention: Drug: Control arm
  • Experimental: Experimental arm
    Neoadjuvant FOLFOXIRI x4 cycles, then capecitabine-radiotherapy and postoperative chemotherapy
    Intervention: Drug: Experimental arm
Publications * Not Provided

*   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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 23, 2019)
72
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 31, 2023
Estimated Primary Completion Date March 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Able to provide written informed consent
  • Age >= 18 years of either sex.
  • ECOG performance status 0-1
  • Measurable disease by RECIST 1.1 criteria.
  • Histologically confirmed rectal adenocarcinoma (defined as either mid- or low rectal cancer that is located within 12 cm from the anal verge OR below the peritoneal reflection) that is previously untreated.
  • 'High risk' rectal cancer, or rectal cancers that are considered marginally perable where there is a significant risk of positive surgical margin:
  • T3 or T4, and / or
  • Tumour infiltrating perirectal fat and/ or mesorectal fascia, and / or Involvement of pelvic lymph nodes, and/or
  • Tumour invading surrounding structures or peritoneum or vasculature.
  • Adequate bone marrow, renal and hepatic function as defined by: absolute neutrophil count >= 1.5 x 109/L, hemoglobin >= 9 g/L, platelets >= 100 x 109/L, serum creatinine level < 1.5 x ULN (or calculated creatinine clearance >=50 ml/min, whichever is worse), total bilirubin <=1.5 x the upper limit of normal, alanine aminotransferase (ALT) < 3 upper limit of normal.

Exclusion Criteria:

  • Known distant metastasis, even if the metastasis has been resected.
  • History of another invasive malignancy within the last 5 years, except for treated basal cell carcinoma of the skin, cervical intraepithelial neoplasia, or breast DCIS.
  • Upper rectal cancer that is located above the peritoneal reflection.
  • Patients with synchronous colon and rectal cancers are not excluded as long as: (1) these tumors are considered as two separate primaries (i.e. not metastasis or a contiguous part of a large primary), (2) both tumors are not causing imminent obstruction; (3) pelvic radiotherapy is not considered a contraindication.
  • Primary tumour associated with any one of the following features:Frank intestinal obstruction, or
  • Endoscope unable to pass through the tumour's lumen plus worsening local obstructive symptoms. Note: Patients with such features should be assessed by the surgical team regarding stomal bypass prior to study enrolment. Such patients can still be considered for study enrolment after undergoing stomal bypass.
  • Known hypersensitivity reaction to the study drugs (i.e. fluoropyrimidine, irinotecan, oxaliplatin)
  • Known peripheral neuropathy of grade 2 or more in severity.\ -Patients who have received an experimental anticancer therapy within the last 28 days.
  • Previous pelvic radiotherapy
  • Previous oxaliplatin or irinotecan for the treatment of colon or rectal cancer.
  • Patient with hip prosthesis
  • Major surgery (i.e. requiring general anaesthetics) within the last 28 days. Exception: Any patient who underwent stomal bypass for obstructing primary tumour within the last 14 days are still eligible, as long as the patient has sufficiently recovered from the surgery at the investigator's discretion.
  • Known cardiac disease that is symptomatic or poorly controlled, including cardiac failure, arrhythmia or ischemic heart disease.
  • Myocardial infarction or cerebrovascular accident within the last 12 months.
  • Intercurrent infections or medical illnesses that are serious/ potentially life-threatening and require ongoing treatment.
  • Patients who are unable to take capecitabine tablets uncrushed by the oral route (e.g. enteral feeding). Patients with significantly impaired gastrointestinal integrity and absorption are excluded.
  • Patients with known and untreated bilateral hydronephrosis and/or hydroureters (or unilateral hydronephrosis and/or hydroureters in any patient with a single kidney) are excluded. The obstruction should be treated with ureteric stent(s) or percutaneous nephrostomy(s) prior to study enrolment. Patients with unilateral hydronephrosis and/or hydroureters and adequate renal function (i.e. as stated in the eligibility criteria: serum creatinine level < 1.5 x ULN, or calculated creatinine clearance >=50 ml/min - whichever is worse) are not excluded.
  • Patients on warfarin therapy. Patients on low molecular weight heparin are not excluded.
  • Pregnant or lactating women.
  • Patients with reproductive potential who are not willing to use barrier method of birth control.
  • Patients who are unable to provide written informed consent, or to comply with study requirements as judged by the investigator.
  • Patients who refuse surgical treatment of the rectal cancer.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Brigette MA, MD 35052118 brigette@clo.cuhk.edu.hk
Contact: Jane Koh, RN 35051142 jane@clo.cuhk.edu.hk
Listed Location Countries  ICMJE Hong Kong
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03997435
Other Study ID Numbers  ICMJE COL026
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 CCTU, Chinese University of Hong Kong
Study Sponsor  ICMJE CCTU
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Chinese University of Hong Kong
Verification Date October 2020

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