FOLFOXIRI With or Without Intensification for Rectal Cancer

A Randomized Study of Neoadjuvant Chemoradiotherapy With or Without Intensification With the FOLFOXIRI Chemo-regimen for High-risk Locally Advanced Rectal Cancer

Pathologic complete response rate

Study Overview

• Status: Recruiting
• Conditions: Rectal Cancer
• Intervention / Treatment: Drug: Control arm; Drug: Experimental arm

• Study Type: Interventional
• Enrollment (Anticipated): 72
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jane KOH, RN; Phone Number: 35051142; Email: jane@clo.cuhk.edu.hk
• Study Contact Backup: Name: Brigette MA, MD; Phone Number: 35052118; Email: brigette@clo.cuhk.edu.hk

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Recruiting
    • The Chinese University of Hong Kong
    • Contact: Jane KOH, RN; Phone Number: 35051142; Email: jane@clo.cuhk.edu.hk
    • Contact: Brigette Ma, MD; Phone Number: 3505 2118; Email: brigette@clo.cuhk.edu.hk
  • Hong Kong, Hong Kong
    • Recruiting
    • Department of Clinical Oncology, Queen Mary Hospital
    • Contact: Kin Sang LAU, MBBS; Phone Number: +852 2255 6220; Email: oncology@hku.hk
    • Contact: Michael WONG, BSc; Phone Number: +852 2255 4216; Email: xmichael@hku.hk
  • Hong Kong, Hong Kong
    • Recruiting
    • Department of Oncology, Princess Margaret Hospital
    • Contact: Dominic C Chan, FHKAM(Radiology) (HK); Phone Number: 2781 +852 2990 1111; Email: ccw319@ha.org.hk
    • Contact: Colin K Liu, B.A.Sc(Toronto); Phone Number: 2393 +852 2990 1111; Email: lkm688@ha.org.hk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rate of pathologic complete response	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Rate of overall survival	5 years
Rate of circumferential resection margin (CRM) clearance	2 years
Rate of tumour downstaging	2 years
Number of Participants with Adverse Events	2 years
Time to local (and distant) recurrence	5 years
Number of response to neoadjuvant therapy	2 years
Rate of tumour regression grade	2 years
Number of objective tumour response	2 years
Rate of disease-free survival, relapse-free survival	5 years
Number of patients with 30-days post-operative mortality	1 month
Rate of compliance to study treatment	2 years

Collaborators and Investigators

• Sponsor: CCTU

Study record dates

Study Major Dates

• Study Start (Actual): September 10, 2019
• Primary Completion (Anticipated): March 31, 2024
• Study Completion (Anticipated): March 31, 2025

Study Registration Dates

• First Submitted: June 19, 2019
• First Submitted That Met QC Criteria: June 23, 2019
• First Posted (Actual): June 25, 2019

Study Record Updates

• Last Update Posted (Estimate): May 4, 2023
• Last Update Submitted That Met QC Criteria: May 3, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms
• Other Study ID Numbers: COL026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No