Study of Therapeutic Targets Tailored Ch and IMRT as Neoadjuvant Treatment in Rectal Carcinoma Patients (TT)

Prospective Pilot Study of Therapeutic Targets (TT) Tailored Chemotherapy (Ch) and Intensity Modulated Radiotherapy (IMRT) as Neoadjuvant Treatment in Patients With Rectal Carcinoma

The parameter that best correlates with 5 years disease-free survival (DFS ) in patients (pts) with localized rectal cancer (RC) is the pathological TNM staging (ypTNM) after chemo-radiotherapy (Ch-RT). DFS is 97% in pts with ypT0N0M0 = ypCR and 42% in pts with ypN +. Standard 5-FU Ch-RT achieves 15% of ypCR. The use of IMRT achieves a high proportion of ypCR . This study aimed to demonstrate in a prospective manner the feasibility of personalizing Ch regimen base in TT in combination with IMRT in patients with RC. Secondary objectives included the number of ypCR and safety.

Study Overview

• Status: Completed
• Conditions: Rectal Cancer
• Intervention / Treatment: Drug: Therapeutic target tailored chemotherapy

Detailed Description

The parameter that best correlates with DFS in patients (pts) with localized rectal cancer (RC) is the pathological TNM staging (ypTNM) after chemo-radiotherapy (Ch-RT).Tumor regression grading (TRG) after Ch-RT has been correlated with DFS , 86% for TRG 4, 75% for grouped TRG 2 + 3, and 63% for grouped TRG 0 + 1 but this is not as good as ypTNM to predict pts outcome.

Standard 5-FU or capecitabine Ch-RT achieves 15% of ypCR with diarrhea and proctitis as the main grade 3 toxicities in the range of 10-15% . With the combination of oxaliplatin and capecitabine pCR rates are the same but the toxicity is the range of 25%. IMRT studies reported 30% ypCR but with 30-40% grade 3 toxicities Last years strategies have explored ways to integrate additional chemotherapeutic agents as capecitabine , oxaliplatin, irinotecan, bevacizumab and cetuximab in Ch-RT regimens and to find biomarkers of their effectiveness , but always in a retrospective way.

Our hypothesis is that with the actual knowledge and technology, a prospective tailored chemotherapy selection in combination with IMRT is feasible and could improve the outcome of patients with rectal cancer.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28050
    • Centro Integral Oncologico Clara Campal

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:

• Histologic diagnosis of rectal adenocarcinoma.
• Clinical stage II or III.
• Feasible patient for neoadjuvant Ch-RT.
• Availability of tumor tissue or possibility of a tumor biopsy to define therapeutic targets.
• Informed written consent was obtained from all patients

Exclusion Criteria:

• Contraindication to the administration of any of the drugs used in the study capecitabine, irinotecan, oxaliplatin, cetuximab or bevacizumab.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: TT tailored Ch plus IMRT

Drug: Therapeutic target tailored chemotherapy; All pts were treated with Capecitabine (Cap) 625-825 mg/m2/12h M-F. Ch combination schema was customized based on: Top- 1 +: Irinotecan (I) 50mg/m2 / in weekly. Top-1 - and ERCC-1 - : Oxaliplatin (O) 50gm/m2/ weekly. Top- 1 - and ERCC-1 + : Neither I nor O. K-Ras or b-Raf mutated (m) : Bevacizumab (B) 5mg/kg every two weeks. K-Ras and B-Raf native (n): Cetuximab (C) 400/250mg/m2 weekly or B (investigator option). Figure 1. When Cap was in combination with O or I the 625mg/m2 dose was chosen. When Cap was the only chemotherapy agent in combination with B or C the 825mg/m2 dose was chosen; Other Names: 5-FU; Oxaliplatin; CPT-11; Therapeutic targets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ypTN	pathology TN after neoadjuvant treatment and surgery	Up to 1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility	Days needed to full set of TT analys. Days from signed informed consent to first day of Ch-RT treatment Number of patinets who complet the Ch-RT treatment and go to surgery as planned.	Up to 3 months

Collaborators and Investigators

• Sponsor: Grupo Hospital de Madrid
• Investigators: Principal Investigator: Antonio Cubillo, MD.PhD, Centro Integral Oncologico Clara Campal

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (Actual): April 1, 2011
• Study Completion (Actual): April 1, 2011

Study Registration Dates

• First Submitted: May 31, 2011
• First Submitted That Met QC Criteria: June 2, 2011
• First Posted (Estimate): June 3, 2011

Study Record Updates

• Last Update Posted (Estimate): June 3, 2011
• Last Update Submitted That Met QC Criteria: June 2, 2011
• Last Verified: October 1, 2009

More Information

Terms related to this study

• Keywords: Rectal cancer, Chemoradiotherapy, target therapy
• 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; Antineoplastic Agents; Oxaliplatin
• Other Study ID Numbers: 62 202-878