Concurrent Chemoradiation With Concomitant Boost In Locally Advanced Rectal Cancer

Phase 2

Completed

• Conditions: Rectal Neoplasms
• Interventions: Radiation: Radiotherapy; Drug: Tom-OX

• Registration Number: NCT02723253
• Lead Sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna

Brief Summary

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.

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 Timeline

• Study Start: 2005-01
• Primary Completion: 2008-01
• Study Completion: 2012-02
• Status Verified: 2016-03
• Study First Submitted: 2016-03-19
• Study First Submitted QC: 2016-03-29
• Last Update Submitted: 2016-03-29
• Study First Posted: 2016-03-30
• Last Update Posted: 2016-03-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 18

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Radiotherapy plus Tom-Ox	Radiotherapy	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.
Radiotherapy plus Tom-Ox	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.

Primary Outcome Measures

Name	Time	Method
Number of patients defined as good responders (G1 or G2) according to the Mandard regression grading system.	8 weeks after chemo-radiotherapy	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.

Secondary Outcome Measures

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