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

Rectal Cancer Clinical Trial

— TT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01366118
• Other study ID #: 62 202-878
• Status: Completed
• Phase: N/A
• First received: May 31, 2011
• Last updated: June 2, 2011
• Start date: October 2009
• Est. completion date: April 2011

Study information

• Verified date: October 2009
• Source: Grupo Hospital de Madrid
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: April 2011
• Est. primary completion date: April 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Rectal Cancer

Intervention

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

Locations

Country	Name	City	State
Spain	Centro Integral Oncológico Clara Campal	Madrid

Sponsors (1)

Lead Sponsor	Collaborator
Grupo Hospital de Madrid

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ypTN	pathology TN after neoadjuvant treatment and surgery	Up to 1 month	No
Secondary	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	No