Concurrent Chemoradiation With Concomitant Boost In Locally Advanced Rectal Cancer

Concurrent Chemoradiation With Concomitant Boost In Locally Advanced Rectal Cancer: A Phase II Study.

Neoadjuvant chemoradiation (CRT), is considered the standard treatment of locally advanced rectal cancer with a positive impact on locoregional control and survival.However, patients with T4 rectal cancer show high risk of local recurrence after conventional treatment. Therefore investigators designed a prospective Phase II study on patients with locally advanced rectal cancer or locally recurrences, to evaluate the efficacy in terms of pathological response and resectability of concomitant boost RT (55 Gy/5 weeks) with concurrent Raltitrexed and Oxaliplatin (Tom-Ox) chemotherapy.

Study Overview

• Status: Completed
• Conditions: Rectal Neoplasms
• Intervention / Treatment: Radiation: Radiotherapy; Drug: Tom-OX

Detailed Description

Neoadjuvant chemoradiation (CRT), is considered the standard treatment of locally advanced rectal cancer with a positive impact on locoregional control and survival. However, patients with T4 rectal cancer show high risk of local recurrence (LR) after conventional treatment. This was a prospective Phase II study on patients with locally advanced rectal cancer or locally recurrences, to evaluate the efficacy in terms of pathological response and resectability of concomitant boost RT (55 Gy/5 weeks) with concurrent Raltitrexed and Oxaliplatin (Tom-Ox) chemotherapy. The primary aim was to assess the pathological complete response rate. Key secondary aim was the resectability. Secondary aims were evaluation of treatment-related acute and late toxicity, local control, disease-free survival and overall survival (OS). The follow-up period of each subjects started after the radiochemotherapy treatment and ended after a maximum of 36 months of observation or until death.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically proven locally advanced (T4N0-2) or locally recurrent rectal adenocarcinoma;
• Age ≥ 18 years;
• Eastern Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

Exclusion Criteria:

• Metastatic patients
• unfit surgery patients,
• pregnant or breast feeding females
• patients with clinically detectable ascites

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Radiotherapy plus Tom-Ox; Patients received concomitant boost RT (55 Gy/5 weeks) with concurrent Tom-Ox chemotherapy. The concurrent chemotherapy consisted of 15 min intravenous infusion Raltitrexed (Tomudex ®) 3 mg/m2 and a two-hours intravenous infusion of Oxaliplatin (Eloxatin ®) at 130 mg/m 2, 20 min after raltitrexed, on days 1, 17, 35.

Radiation: Radiotherapy; Radiotherapy was applied as conformal 3-D technique and was delivered with photon energies of 10 - 15 MV. The beams were delivered by an Elekta Precise Linac equipped with standard multi leaf collimators (MLC). A daily online check of isocenter position was performed using portal imaging, with set-up correction in case of displacement > 0.5 cm in any direction. Radiation dose delivered to PTV2 was 45 Gy (1.8 Gy/fraction) with a concomitant boost dose to the PTV1 of 10 Gy with accelerated fractionation at 2.2 Gy/fraction, five consecutive days for week.; Drug: Tom-OX; The concurrent chemotherapy consisted of 15 min intravenous infusion Raltitrexed (Tomudex ®) 3 mg/m2 and a two-hours intravenous infusion of Oxaliplatin (Eloxatin ®) at 130 mg/m 2, 20 min after raltitrexed, on days 1, 17, 35.; Other Names: Tomudex ®, Eloxatin ®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients defined as good responders (G1 or G2) according to the Mandard regression grading system.	Pathologic responses of the primary tumours were defined according to the Mandard regression grading system: grade 1 was recorded when no tumour cells remained in the primary tumour and lymph nodes (pCR); grade 2 was characterized by the presence of rare residual cancer cells scattered through the fibrosis; grade 3 was characterized by an increase in the number of residual cancer cells, but fibrosis still predominated; grade 4 showed residual cancer outgrowing fibrosis; and grade 5 was characterized by an absence of regressive changes. Good responders were defined those patients with a pathologic response with Mandard G1 or G2 and poor responder patients with Mandard G3, G4 or G5.	8 weeks after chemo-radiotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients in which a surgical resection was feasible		8 weeks after chemo-radiotherapy
Number of participants with treatment-related adverse events as assessed by CTCAE v3.0	CTCAE v 3.0 was used to score acute and late radiation toxicity.	Up to 36 months. In details, follow-up examinations were performed 4 weeks after surgery and every 6 months until the established length of follow-up or death.
The number of patients without disease (i.e. rectal cancer) during the follow-up.	The disease-free survival (DFS) was defined as the time from the diagnosis to the documented local or distant recurrence or last follow-up.	Up to 36 months.
The number of patients still alive at the end of follow-up	The overall-survival (OS) was defined as the time from the diagnosis until death for any cause or the last follow-up.	Up to 36 months

Collaborators and Investigators

• Sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna
• Investigators: Study Director: Alessio G Morganti, Prof, Division of Radiation Oncology, S.Orsola-Malpighi Hospital, Bologna, Italy

Study record dates

Study Major Dates

• Study Start: January 1, 2005
• Primary Completion (Actual): January 1, 2008
• Study Completion (Actual): February 1, 2012

Study Registration Dates

• First Submitted: March 19, 2016
• First Submitted That Met QC Criteria: March 29, 2016
• First Posted (Estimate): March 30, 2016

Study Record Updates

• Last Update Posted (Estimate): March 30, 2016
• Last Update Submitted That Met QC Criteria: March 29, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: chemotherapy; radiotherapy; rectal cancer; Oxaliplatin; Raltitrexed
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Folic Acid Antagonists; Raltitrexed
• Other Study ID Numbers: TOMOX Rectal Study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO