Re-irradiation for Pelvic Recurrences in Rectal Cancer Patients

Study Overview
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Brief Summary
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This study investigates the potential benefit of re-irradiation of patients with locally advanced rectal recurrences, by a prospective phase II clinical, imaging and translational research study.

Detailed Description
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The overall purpose of this trial is to evaluate the efficacy of re-irradiation of patients with locally advanced rectal cancer (LRRC) recurrences who previously received pelvic irradiation. Patients with potentially resectable LRRC will be treated with hyperfractionated Intensity-Modulated Radiotherapy consisting of 40.8 Gy in 1.2 fractions twice daily with concomitant oral capecitabine followed by surgery, when feasible.

Official Title
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External Beam Radiotherapy for Pelvic Recurrences in Rectal Cancer Patients Previously Treated With Radiotherapy

Conditions
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Rectal Cancer, Recurrence, Radiation Toxicity

Intervention / Treatment
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* Radiation: Hyperfractionated external beam radiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Locally recurrent rectal cancer Previous pelvic RT for rectal cancer and surgery Potentially resectable by MRI and palpation by MDT evaluation Absence of non-resectable distant metastases by PET-CT Age ≥ 18 Adequate organ function Acceptable bowel and bladder function Acceptance for TR sampling Exclusion Criteria: Central small recurrences deemed immediate resectable Previous radiotherapy <12 month prior to recurrence Non-resectable systemic or regional disease Unable to undergo MRI or PET-CT Medical comorbidities precluding radical surgery

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Patients are enrolled according to protocol criteria for hyperfractionated IMRT re-irradiation.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Single<br>Re-irradiation consisting of hyperfractionated IMRT, 40.8 Gy in 1.2 fractions twice daily 5/7 days weekly, with oral capecitabine 825 mg/m2 BID on radiotherapy treatment days. Re-staging performed 4-6 weeks after the last dose, followed by surgery, when feasible. | Radiation: Hyperfractionated external beam radiation<br>* 40.8Gy/34 fractions (1.2Gy BID 5/7 days with minimum 6 hours interval) Concurrent capecitabine (825 mg/m2 BID 5/7 days)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resection rate | Rate of complete pathological resection R0 | At surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physician reported Toxicity | Clinical and laboratory AEs (Adverse Events) will be graded according to NCICTCAE (version 4.0). | Acute and late toxicity evaluations during and at 6,12 and 36 months post surgery | 
| QoL assessment according to QLQ-CR29 | Assesment of QoL according to EORTC guidelines. The EORTC QLQ-CR29 is a tumor-specific health related QoL questionnaire module for CRC patients. Patients are asked to indicate their symptoms during the past week(s). According to EORTC guidelines, scores can be reported as frequencies of raw scores or scores can be linearly transformed to provide a score from 0 to 100. Higher scores represent better functioning on the functional scales and a higher level of symptoms on the symptom scales. | Pre-treatment and 12 months post surgery | 
| QoL assessment according to EORTC QLQ-C30 | Assesment of QoL according to EORTC guidelines. The EORTC QLQ-CR30 is a general health related QoL questionnaire. Patients are asked to indicate their symptoms during the past week(s). According to EORTC guidelines, scores can be reported as frequencies of raw scores or scores can be linearly transformed to provide a score from 0 to 100. Higher scores represent better functioning on the functional scales and a higher level of symptoms on the symptom scales. | Pre-treatment and 12 months post surgery | 
| Recurrence rate | Rate of re-recurrence | Rate of re-recurrence at 6, 12 and 36 months post surgery. | 
| Comparative dose planning study | Potential organ at risk sparing when comparing photons vs protons - comparative dose planning | The VMAT plans generated before treatment start (baseline) is compared to IMPT plans. |