Safety and Efficacy Study to Compare Capecitabine + Bevacizumab Versus Capecitabine, Concomitantly With Radiotherapy as Neoadjuvant Treatment for Patients With Localized and Resectable Rectal Cancer

NCT01043484 | Completed Phase 2

• 2 other identifiers: TTD-08-05EudraCT: 2009-010192-24
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to evaluate the efficacy and safety of the combination of capecitabine + bevacizumab concomitantly with radiotherapy versus capecitabine concomitantly with radiotherapy, as neoadjuvant treatment for patients with localized and resectable rectal cancer.

Conditions

Rectal Cancer

Keywords

Resectable rectal cancer; Radiotherapy; Bevacizumab; Capecitabine

Outcome Measures

Primary Outcomes (1)

• Rate complete pathologic responses

  17 months

Secondary Outcomes (8)

• Disease free survival at 3 and 5 years

  78 months

• Rate of local and distant recurrence at 3 and 5 years

  78 months

• Overall survival at 3 and 5 years

  78 months

• R0 resection rate.

  17 months

• Adverse events

  17 months

Study Arms (2)

A

EXPERIMENTAL

Bevacizumab + Capecitabine + Radiotherapy

Drug: Bevacizumab + Capecitabine + Radiotherapy

B

ACTIVE COMPARATOR

Capecitabine + Radiotherapy

Drug: Capecitabine + Radiotherapy

Interventions

Bevacizumab + Capecitabine + Radiotherapy DRUG

Bevacizumab (5 mg/kg; days 1, 15 and 29) Capecitabine (825 mg/m2/12h, 5 days/w) Radiotherapy (45 Gy in sessions of 1.8 Gy 5 times/w for 5 weeks)

A

Capecitabine + Radiotherapy DRUG

Capecitabine (825 mg/m2/12h, 5 days/w) and Radiotherapy (45 Gy in sessions of 1.8 Gy 5 times/w for 5 weeks)

B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent
• Age ≥18 years
• ECOG ≤ 1
• Histologically confirmed carcinoma of the rectum
• Localized and resectable rectal cancer
• No metastatic disease
• Measurable disease
• Life expectancy more than 4 months
• Non prior treatment for rectal cancer
• Adequate haematological function: leu ≥ 4x 109 /l, Hb ≥10 gr/dl, neutropils≥ 1,5 x 109 /l and platelets ≥100 x 109 /l
• Adequate renal function: creatinine ≤ 106 umol/l or calculated creatinine clearance \> 50 mL/min
• Adequate liver function: AST, ALT and alkaline phosphatase ≤2.5 x UL, bilirubin ≤1.5 x UL
• Adequate nutritional weight loss \<10% of regular weight and albumin ≥ 35 g/l

You may not qualify if:

• Unresectable rectal cancer
• Past or current history (within the last 5 years prior to treatment start) of other malignancies.
• Patients of childbearing potential not willing to use effective means of contraception.
• Clinically significant cardiovascular disease
• Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome or inability to take oral medication.
• Patients subjected to organ allografts who require immunosuppressive treatment.
• Severe, non-cicatrized osseous fractures, wounds or ulcers.
• Indications of hemorrhagic diathesis or coagulopathy.
• Severe, uncontrolled intercurrent infections or other severe, uncontrolled concomitant diseases.
• History of unexpected severe reactions to treatment with fluoropyrimidines or known deficiency dihydropyrimidine dehydrogenase deficiency (DPD).
• Patients subjected to a major surgical procedure, open biopsy or who have had significant traumatic lesions within the 28 days prior to beginning the treatment of the study or in whom it is foreseen that a major surgical procedure will be necessary during the course of the study; fine-needle aspiration within the 7 days prior to beginning the treatment of the study.
• Current or recent use (within the 10 days prior to beginning the treatment of the study) of oral or parenteral anticoagulants at complete doses or thrombolytic agents. The use of low doses of warfarin is allowed, with an International Normalized Ratio \[INR\] of \< 1.5.
• Daily chronic treatment with high doses of aspirin (\> 325 mg/day) or non-steroid anti-inflammatory medications (which inhibit the platelet function at doses used for treating chronic inflammatory diseases).
• Patients who have received any drug or agent/procedure under research, i.e., who have participated in another clinical trial during the 4 weeks prior to beginning the treatment with the medications of the study
• Any psychological, familiar conditions suggesting that the patient will not be able to complete the study

Sponsors & Collaborators

• Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD): lead
• Hoffmann-La Roche: collaborator

Study Sites (1)

Spanish Cooperative Group for Gastrointestinal Tumour Therapy

Madrid, 28046, Spain

Location

Related Publications (2)

• Salazar R, Capdevila J, Manzano JL, Pericay C, Martinez-Villacampa M, Lopez C, Losa F, Safont MJ, Gomez-Espana A, Alonso-Orduna V, Escudero P, Gallego J, Garcia-Paredes B, Palacios A, Biondo S, Gravalos C, Aranda E; Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD). Phase II randomized trial of capecitabine with bevacizumab and external beam radiation therapy as preoperative treatment for patients with resectable locally advanced rectal adenocarcinoma: long term results. BMC Cancer. 2020 Nov 27;20(1):1164. doi: 10.1186/s12885-020-07661-z.

  PMID: 33246428 DERIVED

• Salazar R, Capdevila J, Laquente B, Manzano JL, Pericay C, Villacampa MM, Lopez C, Losa F, Safont MJ, Gomez A, Alonso V, Escudero P, Gallego J, Sastre J, Gravalos C, Biondo S, Palacios A, Aranda E. A randomized phase II study of capecitabine-based chemoradiation with or without bevacizumab in resectable locally advanced rectal cancer: clinical and biological features. BMC Cancer. 2015 Feb 26;15:60. doi: 10.1186/s12885-015-1053-z.

  PMID: 25886378 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Bevacizumab; Capecitabine; Radiotherapy

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Therapeutics

Study Officials

• Ramón Salazar

  Institut Català d´Oncologia (ICO) L'Hospitalet. Barcelona. Spain

  STUDY CHAIR

• Cristina Grávalos

  Hospital 12 Octubre. Madrid. Spain

  STUDY CHAIR

• Sebastiano Biondo

  Hospital Universitario de Bellvitge.Barcelona. Spain

  STUDY CHAIR

• Amalia Palacios

  Hospital Universitario Reina Sofía. Córdoba. Spain

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 30, 2009
• First Posted: January 6, 2010
• Study Start: December 1, 2009
• Primary Completion: January 1, 2013
• Study Completion: August 1, 2016
• Last Updated: October 19, 2016

Record last verified: 2016-10

Locations

ES (1)