GRECCAR 15 is focused on Locally Recurrent Rectal Cancer (LRRC) for patients with previous pelvic radiotherapy for the primary rectal cancer. This situation leads to a 20% higher risk of non-curative resection for the LRRC management (R1 status) impacting significantly the overall survival. The widespread use of neoadjuvant radiotherapy for primary rectal cancer introduces this new problem: the treatment of LRRC in previously irradiated area. The objective of GRECCAR 15 is to assess the efficacy of neoadjuvant chemotherapy followed by pelvic reirradiation versus neoadjuvant chemotherapy alone on the rate of curative surgery (R0) in previously irradiated patients with LRRC.
The incidence of rectal cancer in the European Union is 15-25/100 000 per year. There is a 5-10% rate of locally recurrent rectal cancer (LRRC), with an overall survival rate of 40% at 5 years after complete resection. Curative surgery of LRRC requires multi-visceral resections which are associated with significant post-operative morbidity of 60%. Despite the combination of a potential curability and the high post-operative morbidity, there are currently neither good data from prospective randomized studies regarding optimum preoperative treatments for LRRC nor is there data assessing the efficacy of response to any such treatments. Moreover, the widespread use of neoadjuvant radiotherapy for primary cancer introduced a new problem: the treatment of LRRC in previously irradiated area. Some studies investigated various modalities of reirradiation and showed acceptable late toxicity and encouraging outcome. GRECCAR 15 would be the first prospective randomized trial so far to evaluate the interest of pelvic reirradiation for LRRC, in previously irradiated patients. The objective is to assess the efficacy of neoadjuvant chemotherapy followed by pelvic reirradiation versus neoadjuvant chemotherapy alone on the rate of curative surgery (R0) in previously irradiated patients with LRRC. Patients will be followed every 4 months during 2 years, and every 6 months the last year with chest, abdominal and pelvic scan and tumour markers.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
58
* oxaliplatin: 85 mg/m2 * irinotecan: 180 mg/m² * folinic acid: 400 mg/m2 * 5FU : 400 mg/m2 (bolus) * 5FU : 2400 mg/m2 (continuous infusion)
Reirradiation consists in conformational intensity modulated external irradiation (Intensity-modulated radiotherapy Volumetric Modulated Arc Therapy or tomotherapy) delivering a 30.6 Gy dose with high-energy photons in fractions of 1.8 Gy per day (17 fractions) 5 days a week With Concomitant chemotherapy including Capecitabine 1600 mg/m²/day, five days a week.
Surgery will be performed at: * Arm A: 8 weeks (±1) after the end of treatment * Arm B: 6 weeks (±1) after the end of treatment Surgical procedures are defined into three categories: * Total mesorectal excision (TME) * Extended-TEM (e-TME) * Pelvic exenteration (PE)
Institut Sainte Catherine
Avignon, France
CHU Bordeaux
Bordeaux, France
CHU Grenoble
Grenoble, France
Centre Oscar Lambret
Lille, France
Hospices Civils de Lyon, HCL
Lyon, France
Institut Paoli Calmette
Marseille, France
Institut du Cancer de Montpellier
Montpellier, France
CHRU Nancy
Nancy, France
Groupe Hospitalier Paris Saint-Joseph
Paris, France
CHU Rennes
Rennes, France
...and 3 more locations
Proportion of curative surgery
To determine the rate of R0 resection
Time frame: At surgery, expected average 6 to 8 weeks after neoadjuvant treatment
Disease Free Survival
Rate of disease-free survival at 3 years
Time frame: From surgery until 3 years of follow-up
Overall Survival
Rate of overall survival at 3 years
Time frame: From surgery until 3 years of follow-up
Surgical morbidity
To analyse surgical morbidity (Dindo classification) during first 30 days after the surgery
Time frame: From surgery until 30 days after surgery
Surgical mortality
To analyse surgical mortality (Dindo classification) during first 30 days after the surgery
Time frame: From surgery until 30 days after surgery
Compliance to treatment
Proportion of patients receiving full allocated neoadjuvant treatment
Time frame: From beginning of neoadjuvant treatment until surgery, expected average 20 weeks after neoadjuvant treatment
Proportion of good tumor response
Rate of tumor with a decreasing size of 50% at least after preoperative treatment at MRI
Time frame: At 6 weeks (Arm A) and 4 weeks (Arm B) after neoadjuvant treatment
Quality of life (QLQ CR-30)
The scores of questionnaire QLQ C-30 will be examined The EORTC QLQ-C30 is a patients self-rating questionnaire that measures physical, role, social, emotional, and cognitive functions as well as overall QoL. 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 of the symptom scales.
Time frame: Before neoadjuvant treatment, before surgery, 4 months, one year and two years after surgery
Quality of life (QLQ CR-29)
The scores of questionnaire QLQ CR-29 will be examined. The EORTC QLQ-CR29 has five functional and 18 symptom scales. 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 of the symptom scales.
Time frame: Before neoadjuvant treatment, before surgery, 4 months, one year and two years after surgery
Tolerance to treatment
Number of patients with adverse events
Time frame: From beginning of neoadjuvant treatment until 1 year after surgery
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.