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

NCT ID: NCT01653301

Last Updated: 2012-07-31

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 616 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-10-31

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.

Conditions

Rectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

XELOX-RT

• 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).

Group Type: EXPERIMENTAL

XELOX RT

Intervention Type: 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).

XELAC-RT

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).

Group Type: ACTIVE_COMPARATOR

XELAC RT

Intervention Type: 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).

Interventions

XELAC RT

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).

Intervention Type: DRUG

XELOX RT

• 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).

Intervention Type: DRUG

Eligibility Criteria

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.

• 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

• 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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Catholic University of the Sacred Heart

OTHER

Sponsor Role: lead

Responsible Party

Vincenzo Valentini

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Catholic University of Sacred Heart

Rome, Italy, Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Vincenzo Valentini, MD

Role: CONTACT

Phone: +390630155226

Email: vvalentini@rm.unicatt.it

Facility Contacts

Vincenzo Valentini, MD

Role: primary

References

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.

Reference Type: DERIVED

PMID: 31005204 (View on PubMed)

Other Identifiers

515(A1144)/2005

Identifier Type: -

Identifier Source: org_study_id