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

NCT ID: NCT01366118

Last Updated: 2011-06-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-10-31
• Study Completion Date: 2011-04-30

Brief 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.

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.

Conditions

Rectal Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

TT tailored Ch plus IMRT

Group Type: EXPERIMENTAL

Therapeutic target tailored chemotherapy

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

Other Intervention Names

Therapeutic targets; Oxaliplatin; CPT-11; 5-FU

Eligibility Criteria

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.

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

Sponsors

Grupo Hospital de Madrid

OTHER

Sponsor Role: lead

Responsible Party

Centro Integral Oncológico Clara Campal

Principal Investigators

Antonio Cubillo, MD.PhD

Role: PRINCIPAL_INVESTIGATOR

Centro Integral Oncológico Clara Campal

Locations

Centro Integral Oncológico Clara Campal

Madrid, Madrid, Spain

Countries

Spain

Other Identifiers

62 202-878

Identifier Type: -

Identifier Source: org_study_id