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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01366118
Recruitment Status : Completed
First Posted : June 3, 2011
Last Update Posted : June 3, 2011
Information provided by:
Grupo Hospital de Madrid

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.

Condition or disease Intervention/treatment Phase
Rectal Cancer Drug: Therapeutic target tailored chemotherapy Not Applicable

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  (Clinical Trial)
Actual Enrollment : 16 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : October 2009
Actual Primary Completion Date : April 2011
Actual Study Completion Date : April 2011

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:
  • Therapeutic targets
  • Oxaliplatin
  • CPT-11
  • 5-FU

Primary Outcome Measures :
  1. ypTN [ Time Frame: Up to 1 month ]
    pathology TN after neoadjuvant treatment and surgery

Secondary Outcome Measures :
  1. Feasibility [ Time Frame: Up to 3 months ]
    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.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01366118

Centro Integral Oncológico Clara Campal
Madrid, Spain, 28050
Sponsors and Collaborators
Grupo Hospital de Madrid
Principal Investigator: Antonio Cubillo, MD.PhD Centro Integral Oncológico Clara Campal

Responsible Party: Fundación Hospital de Madrid, Centro Integral Oncológico Clara Campal Identifier: NCT01366118     History of Changes
Other Study ID Numbers: 62 202-878
First Posted: June 3, 2011    Key Record Dates
Last Update Posted: June 3, 2011
Last Verified: October 2009

Keywords provided by Grupo Hospital de Madrid:
Rectal cancer, Chemoradiotherapy, target therapy

Additional relevant MeSH terms:
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Antineoplastic Agents