Preoperative Downstaging of Extraperitoneal T3 Rectal Cancer: XELOXRT Versus XELACRT. A Multicenter, Phase III Study

NCT01653301 | Unknown Phase 3

• 1 other identifier: 515(A1144)/2005
• Study Type: interventional
• Target: 616
• Locations: 1 country
• Sites: 1

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

Conditions

Rectal Cancer

Outcome Measures

Primary Outcomes (1)

• Pathological major downstaging

  INTERACT study: evaluation of T pathological major downstaging, considered as the overall rate of any TRG1 or TRG 2 scored patients; LEADER study (optional): To evaluate the impact on local control of local excision in patients who had a major clinical response, evaluated by EUS/ MRI, yN0 evaluated by multislice CT / MRI, and confirmed by TRG 1-2 score.

  15-20 weeks after the randomization

Secondary Outcomes (4)

• Tumor downstaging

  15-20 weeks after the randomization

• sphincter saving surgery

  15-20 weeks after the randomization

• local control

  15-20 weeks after the randomization

• survival

  15-20 weeks after the randomization

Study Arms (2)

XELOX-RT

EXPERIMENTAL

* Xeloda: 1300 mg/m2 chronomodulated (h 8.00 a.m. 25% of total dose ; h 6.00 p.m. 25% of total dose; h 11.00 p.m. 50% of total dose), during the whole treatment time; * Oxaliplatin: 130mg/m2, days 1, 19, 38 RT: pelvic treatment is the same for both arms: 45 Gy are delivered to the whole pelvis at 1.8 Gy daily, 5 times per week; In the XELOX-RT arm a boost of 5.4 Gy is delivered to the mesorectum corresponding to GTV, at 1.8 Gy daily, in 3 fractions, to a total dose of 50.4 Gy. The boost will be delivered at the end of the irradiation of the pelvis (sequential boost).

Drug: XELOX RT

XELAC-RT

ACTIVE COMPARATOR

Xeloda 1650mg/m2 chronomodulated (h 8.00 a.m. 25% of total dose ; h 6.00 p.m. 25% of total dose; h 11.00 p.m. 50% of total dose) during the whole treatment time. RT: pelvic treatment is the same for both arms: 45 Gy are delivered to the whole pelvis at 1.8 Gy daily, 5 times per week. In the XEL-ACRT arm a boost of 10 Gy is delivered to the mesorectum corresponding to the GTV, at 1 Gy for fraction to a total dose of 55 Gy, in 10 fractions over 5 weeks, 2 times a week. The daily dose of the boost will be delivered twice a week immediately after the daily dose administered to the pelvis (concomitant boost).

Drug: XELAC RT

Interventions

XELAC RT DRUG

Xeloda 1650mg/m2 chronomodulated (h 8.00 a.m. 25% of total dose ; h 6.00 p.m. 25% of total dose; h 11.00 p.m. 50% of total dose) during the whole treatment time. RT: pelvic treatment is the same for both arms: 45 Gy are delivered to the whole pelvis at 1.8 Gy daily, 5 times per week. In the XEL-ACRT arm a boost of 10 Gy is delivered to the mesorectum corresponding to the GTV, at 1 Gy for fraction to a total dose of 55 Gy, in 10 fractions over 5 weeks, 2 times a week. The daily dose of the boost will be delivered twice a week immediately after the daily dose administered to the pelvis (concomitant boost).

XELAC-RT

XELOX RT DRUG

* Xeloda: 1300 mg/m2 chronomodulated (h 8.00 a.m. 25% of total dose ; h 6.00 p.m. 25% of total dose; h 11.00 p.m. 50% of total dose), during the whole treatment time; * Oxaliplatin: 130mg/m2, days 1, 19, 38 RT: pelvic treatment is the same for both arms: 45 Gy are delivered to the whole pelvis at 1.8 Gy daily, 5 times per week; In the XELOX-RT arm a boost of 5.4 Gy is delivered to the mesorectum corresponding to GTV, at 1.8 Gy daily, in 3 fractions, to a total dose of 50.4 Gy. The boost will be delivered at the end of the irradiation of the pelvis (sequential boost).

XELOX-RT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Catholic University of the Sacred Heart: lead

Study Sites (1)

Catholic University of Sacred Heart

Rome, Italy, 00168, Italy

RECRUITING

Related Publications (1)

• 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.

  PMID: 31005204 DERIVED

MeSH Terms

Conditions

Rectal Neoplasms

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Central Study Contacts

Vincenzo Valentini, MD

CONTACT

+390630155226; vvalentini@rm.unicatt.it

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: April 30, 2012
• First Posted: July 31, 2012
• Study Start: October 1, 2005
• Primary Completion: December 1, 2012
• Last Updated: July 31, 2012

Record last verified: 2012-07

Locations

IT (1)