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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Rectal Cancer

Intervention / Treatment
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* Drug: Therapeutic target tailored chemotherapy


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TT tailored Ch plus IMRT<br> | Drug: Therapeutic target tailored chemotherapy<br>* 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<br>* Other names: 5-FU;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rectal cancer, Chemoradiotherapy, target therapy