Clinical trial NCT03997435: FOLFOXIRI With or Without Intensification for Rectal Cancer
Official title: A Randomized Study of Neoadjuvant Chemoradiotherapy With or Without Intensification With the FOLFOXIRI Chemo-regimen for High-risk Locally Advanced Rectal Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Rectal Cancer
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
First posted: 2019-06-25
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Pathologic complete response rate


Eligibility 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.

Primary outcomes:
measure: Rate of pathologic complete response
timeFrame: 2 years
Secondary outcomes:
measure: Rate of tumour regression grade
timeFrame: 2 years
measure: Number of objective tumour response
timeFrame: 2 years
measure: Rate of circumferential resection margin (CRM) clearance
timeFrame: 2 years
measure: Rate of tumour downstaging
timeFrame: 2 years
measure: Number of Participants with Adverse Events
timeFrame: 2 years
measure: Rate of overall survival
timeFrame: 5 years
measure: Rate of disease-free survival, relapse-free survival
timeFrame: 5 years
measure: Time to local (and distant) recurrence
timeFrame: 5 years
measure: Number of patients with 30-days post-operative mortality
timeFrame: 1 month
measure: Rate of compliance to study treatment
timeFrame: 2 years
measure: Number of response to neoadjuvant therapy
timeFrame: 2 years
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Department of Clinical Oncology, Queen Mary Hospital
city: Hong Kong
country: Hong Kong
facility: Department of Oncology, Princess Margaret Hospital
city: Hong Kong
country: Hong Kong
facility: The Chinese University of Hong Kong
Study officials:
References: