Resource-Sparing Curative Treatment for Rectal Cancer

International Atomic Energy Agency

Status and phase: Unknown; Phase 3

Conditions: Rectal Carcinoma

Treatments: Radiation: Radiotherapy

Study type: Interventional

Funder types: Other

Identifiers

NCT01459328

E33034

Details and patient eligibility

About

This is a prospective, multicentre, randomized clinical trial comparing two different neo-adjuvant radiation-based strategies prior to intended surgery for locally advanced adenocarcinoma of the rectum.

This trial may establish the investigational therapy to be superior to, or at least not inferior to conventional treatment.

Full description

This phase III randomised clinical trial compares the outcome of two different neo-adjuvant radiation based treatments for locally advanced rectal carcinoma. This encompasses patients at risk for a positive circumfrential resection margin (CRM+) on baseline assessment imaging and pateints identified as being with a T-descriptor T4 at baseline assessment.

The arms compared are as follows:

• The investigational arm: short chemo-radiation course(25Gy in 5 daily fractions over 1 week) +/- surgery.
• The conventional arm: protracted chemo-radiation course (50Gy in 25 daily fractions over 5 weeks combined with chemotherapy)+/- surgery.

The outcomes include four domains: overall survival, biological effect, quality of life and health-related economics.

Enrollment: 350 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 18 years of age or older
• Clinical (i.e. surgical determination) and/or diagnostic image findings consistent with c/uT4 or CRM+ (note that CRM+ must be established by MRI), primary rectal Adenocarcinoma (i.e. histology consistent with origin from rectal mucosa); these constitute LARC for the purpose of this protocol
• Treatment will be directed at the primary cancer, being clinically appropriate and given with an initial intent to cure the patient (this includes accepting up front that radiation and surgery are feasible; for surgery, this means that the patient has been determined fit for major surgery by an anaesthesiologist prior to the request for randomization)
• Performance status is sufficient to undertake the treatment in either arm (KPS>50%)
• Patient is accessible for required follow-up and data collection
• Radiation oncologist expects survival to exceed 6 months from date of diagnosis
• Patient provides informed consent

Exclusion criteria

• Recurrent rectal cancer
• Primary wholly in the sigmoid colon
• Considered to be arising in the anal canal
• Metastatic disease beyond the pelvis (by clinical assessment and/or diagnostic imaging)
• Contraindications to protocol RT or to protocol chemotherapy, such as one or more of the following:
• any prior RT to the pelvis; a solitary pelvic kidney within the intended radiation volume
• consideration by the most responsible radiation oncologist that the treatment volume is too large, or the amount of small bowel or other critical organs within the treatment volume is too much for safe treatment
• significantly abnormal laboratory tests such as impaired renal/liver function
• a haemoglobin that is < 8.0 (or 80, SI) and the patient is not transfused to exceed 8.0 (or 80, SI)
• on-going medications that are not compatible with protocol neo-adjuvant chemotherapy as described in this protocol
• Significant development issues (such as with age < 18 yr)
• Co-morbidity
• Psychiatric diagnosis
• Physical impairment
• Pregnancy or continuing breast-feeding, that precludes administration of protocol treatments, or that precludes data collection (such as likely to preclude follow-up visits or completing questionnaires)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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350 participants in 2 patient groups

Arm A: Conventional Long Course Chemo-Radiation

Active Comparator group

Description:

Conventional long course chemo-radiation

Treatment:

Radiation: Radiotherapy

Radiation: Radiotherapy

Arm B: Short Course Radiation Followed by Chemotherapy

Experimental group

Description:

Experimental short course radiation followed by chemotherapy.

Treatment:

Radiation: Radiotherapy

Radiation: Radiotherapy