Clinical trial NCT01653301: Preoperative Downstaging of Extraperitoneal T3 Rectal Cancer: XELOXRT Versus XELACRT. A Multicenter, Phase III Study
Official title: INTEnsification Radiotherapy With Accelerated Fractionation or ChemoTherapy And Local Excision After 3D External Radio-chemotherapy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Rectal Cancer
Lead sponsor: Catholic University of the Sacred Heart
Sponsor class: OTHER
First posted: 2012-07-31
Enrollment: 616
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: * INTERACT study: to evaluate the pathological response rate in cT3 rectal cancer
* LEADER study: to evaluate the impact on local control of local excision

Detailed description: * INTERACT study: to evaluate the pathological response rate evaluated according to TRG scale comparing accelerated radiotherapy on the gross tumour combined plus standard radiotherapy to the pelvis in association with chronomodulated capecitabine (XELACRT arm) versus oxaliplatin added to standard pelvis radiotherapy and same chronomodulated Capecitabine (XELOXRT arm)
* LEADER study: to evaluate the impact on local control of local excision in patients who had a major clinical response evaluated by MRI and confirmed by TRG 1-2 score.

Eligibility criteria: INTERACT STUDY

Inclusion Criteria:

* Histologically confirmed primary adenocarcinoma of the rectum.
* Tumour within 12 cm of the anal verge by proctoscopic examination or within 10 cm of the anorectal ring by MRI.
* Clinical stages (UICC 1997): cT2N0-2 low located tumour, cT3 N0-2.
* Resectable disease at the routine examination.
* Age \> 18 years.
* Karnofsky Performance Status \> 60.
* WBC \> 4,000 cells/ml, platelets \> 100,000 cells/ml.
* Provision of written informed consent.

Exclusion Criteria:

* Evidence of metastatic (M1) disease. If there were any suspicious findings (i.e. liver metastasis, lung nodule, retroperitoneal adenopathy, etc.) the patient is to be considered as ineligible, unless malignancy is ruled out by tissue documentation (biopsy) before trial therapy is started.
* Previous chemotherapy, immunotherapy, or radiation therapy to the pelvis.
* Multiple primary cancers involving both the colon and rectum that would preclude a patient from being classified as having only rectal cancer.
* Incomplete healing from or other surgery.
* Active inflammatory bowel disease.
* Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal cell carcinoma or cervical cancer in situ.
* Cardiovascular disease with a New York Heart Association Functional Status \> 2.
* Absolute neutrophil count (ANC) \< 4 x 108/L or platelets \< 50 x 108/L.
* Measured Creatinine clearance less than 65ml/min. (no drug dose reduction for lower GFR is allowed).
* ALT or AST \> 2.5 times the ULRR
* Pregnancy or breastfeeding (women of child-bearing potential).
* Any evidence of severe or uncontrolled systemic disease (e.g. unstable or uncompensated respiratory, cardiac, hepatic or renal disease).
* Any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the trial.

LEADER STUDY

Inclusion Criteria

* Stage at the diagnosis: cT3N0. T3 patients at the diagnosis with 3 or less enlarged nodes, evaluated by imaging, and without evidence of the same nodes after radiochemotherapy, could be accrued according to Center decision, but will be analyzed separately.
* Patients with cT2N0, low located tumour, otherwise candidates to a Miles surgical procedure, treated by neoadjuvant chemoradiation and with written consensus;
* Major clinical response after chemoradiation, yT0-1N0; yT2N0 could be accrued according to Center decision, but will be analyzed separately.
* Circumferential extension less than 2 quarters;
* Deep ulcer \< 2 cm of diameter;
* Provision of written informed consent;
* Biopsies are discouraged for the higher risk of following fistulae in irradiated rectum;

Exclusion Criteria:

* pT3;
* Positive margins;
* TRG 3-5;
* Major adverse features: lymphatic vessel invasion, vascular vessel invasion, perineural invasion;

Primary outcomes:
measure: Pathological major downstaging
timeFrame: 15-20 weeks after the randomization
Secondary outcomes:
measure: Tumor downstaging
timeFrame: 15-20 weeks after the randomization
measure: sphincter saving surgery
timeFrame: 15-20 weeks after the randomization
measure: local control
timeFrame: 15-20 weeks after the randomization
measure: survival
timeFrame: 15-20 weeks after the randomization
Other outcomes:
Locations:
city: Rome
country: Italy
facility: Catholic University of Sacred Heart
Study officials:
References:
citation: Valentini V, Gambacorta MA, Cellini F, Aristei C, Coco C, Barbaro B, Alfieri S, D'Ugo D, Persiani R, Deodato F, Crucitti A, Lupattelli M, Mantello G, Navarria F, Belluco C, Buonadonna A, Boso C, Lonardi S, Caravatta L, Barba MC, Vecchio FM, Maranzano E, Genovesi D, Doglietto GB, Morganti AG, La Torre G, Pucciarelli S, De Paoli A. The INTERACT Trial: Long-term results of a randomised trial on preoperative capecitabine-based radiochemotherapy intensified by concomitant boost or oxaliplatin, for cT2 (distal)-cT3 rectal cancer. Radiother Oncol. 2019 May;134:110-118. doi: 10.1016/j.radonc.2018.11.023. Epub 2019 Feb 7.