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Study of Neoadjuvant Chemotherapy With Selective Radiotherapy in Patients With Intermediate-Risk Cancer Rectum Defined by Magnetic Resonance Imaging (MRI)
This study is currently recruiting participants.
Verified by Grupo Espanol Multidisciplinario del Cancer Digestivo, December 2009
First Received: March 23, 2009   Last Updated: December 29, 2009   History of Changes
Sponsor: Grupo Espanol Multidisciplinario del Cancer Digestivo
Collaborator: Royal Marsden NHS Foundation Trust
Information provided by: Grupo Espanol Multidisciplinario del Cancer Digestivo
ClinicalTrials.gov Identifier: NCT00909987
  Purpose

Phase II, Multicenter, Open-label, Non-randomized Study of Neoadjuvant Chemotherapy (CAPECITABINE-OXALIPLATIN + BEVACIZUMAB) with Selective Radiotherapy and Chemotherapy with CAPECITABINE Use in Patients with Intermediate-Risk Cancer of the Rectum Defined by Magnetic Resonance Imaging.


Condition Intervention Phase
Rectum Cancer
Drug: Capecitabine
Drug: Oxaliplatin
Drug: Bevacizumab
Radiation: Radiotherapy
Drug: Capecitabine during all Radiotherapy period
Procedure: Total Mesorectal Excision (TME)
Phase II

Study Type: Interventional
Study Design: Treatment, Open Label, Uncontrolled, Single Group Assignment, Efficacy Study
Official Title: Phase II, Multicenter, Open-label, Non-randomized Study of Neoadjuvant Chemotherapy With Selective Radiotherapy Use in Patients With Intermediate-Risk Cancer of the Rectum Defined by Magnetic Resonance Imaging

Resource links provided by NLM:


Further study details as provided by Grupo Espanol Multidisciplinario del Cancer Digestivo:

Primary Outcome Measures:
  • Efficacy of XELOX/BVZ neoadjuvant therapy with selective radiotherapy use in patients with locally advanced tumors of the rectum, measured in terms of the proportion of responders (PCR + CCR), according to RECIST criteria [ Time Frame: Until the end of study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Study treatment,which selectively omits neoadjuvant irradiation,can achieve a R0= 90% [ Time Frame: At least 3 years for local recurrence and systemic recurrence ] [ Designated as safety issue: Yes ]
  • Rate of local and systemic recurrence [ Time Frame: At least 3 years for local recurrence and systemic recurrence ] [ Designated as safety issue: Yes ]
  • Toxicity of treatment [ Time Frame: At least 3 years for local recurrence and systemic recurrence ] [ Designated as safety issue: Yes ]
  • Rate of surgical complications during postoperative [ Time Frame: At least 3 years for local recurrence and systemic recurrence ] [ Designated as safety issue: Yes ]
  • Profile of gene expression before neoadjuvant treatment [ Time Frame: At least 3 years for local recurrence and systemic recurrence ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 46
Study Start Date: March 2009
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Capecitabine
    PO 1000 mg/m2 bid during day 1 to 15 for 3 cycles (every cycle has 3 weeks)
    Drug: Oxaliplatin
    IV 130 mg/m2 during day 1 for 3 cycles (every cycle has 3 weeks)
    Drug: Bevacizumab
    IV 7.5 mg/Kg during 30 minutes day 1 during 4 cycles (every cycle has 3 weeks)
    Radiation: Radiotherapy
    Total dose 52.5 Gy administered in 2 series during 33 days
    Drug: Capecitabine during all Radiotherapy period
    825 mg/m2 bid
    Procedure: Total Mesorectal Excision (TME)
    4 weeks from the last chemotherapy dose. In those patients who receive radiation TME wil be performed six weeks after
Detailed Description:

XELOX / Bevacizumab will be administrated for 3 cycles over a 9 week period. XELOX without Bevacizumab will be administrated for an additional cycle over a 4 week period. Patients will undergo re-staging within 3 weeks of their 4th cycle of XELOX. This will include MRI of the pelvis. If the reassessment reveals that there has been no disease progression compared to the pre-treatment evaluation and the patient remains a candidate for an R0 resection, the patient will proceed to definitive rectal cancer surgery within 4 weeks from the last chemotherapy dose. If the surgical oncologist's reassessment reveals that the patient is not a candidate for an R0 resection, the patient will proceed to standard pre-operative radiation with synchronous Capecitabine.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient ≥18 years
  • Tumor biopsy with histopathologic confirmation of rectal adenocarcinoma as primary histology
  • Patient with measurable disease at the baseline visit
  • Tumor that meets all the following criteria in high-resolution MRI (3-mm slices) of the pelvis:
  • Distal border of tumor more than 5cm from the external edge of the anus and below the sacral promontory (located in the anatomic rectum). One or two of the following: T3>5mm; Presence of extramural venous invasion; Tumor ≥2 mm from the mesorectal fascia
  • Candidate for complete surgical resection (R0) with sphincter preservation surgery, prior to the administration of any therapy
  • Candidate for systemic therapy with XELOX/BVZ
  • ECOG: 0-2
  • ANC≥1.5 cells/mm3, Hb>8.0 g/dL, platelets>150,000/mm3 in 2 previous weeks
  • Patient who signed the informed consent

Exclusion Criteria:

  • Stage T4.
  • Distant metastases
  • Tumor with an intraperitoneal distal border
  • Tumor presenting initially in a low location and judged, prior to any treatment, to require abdominoperineal resection
  • Previous chemotherapy for colorectal cancer or incomplete recovery from oncologic surgery or other previous major surgery that, in the opinion of the investigator, precludes the use of a combined modality therapy
  • Serum creatinine <1.5 ULN
  • Patient who has received previous pelvic radiotherapy
  • Patient with an uncontrolled infection
  • Presence of a high degree of obstruction (intestinal lumen ≤ 1 cm), unless the patient has undergone protective surgical bypass or an endoscopic stent procedure
  • Pt with a history of an arterial thromboembolic event during the previous year.This includes angina (stable or unstable),myocardial infarction (MI),cerebrovascular accident (CVA),or other relevant history in the opinion of the investigator.Note: A patient with a history of thrombotic events, such as deep venous thrombosis, pulmonary embolism, MI or ACV, within the 6 months preceding recruitment may be considered for participation in the clinical trial if they are receiving stable doses of anticoagulant therapy. Similarly, patients being anticoagulated for atrial fibrillation or other conditions can participate if they are receiving a stable dosage of anticoagulant therapy. Clinicians must consider the higher risk of therapy with BVZ among patients with a history of thromboembolic disorders so the decision to allow the patients to participate remains at the discretion of the physician
  • Previous treatment with another investigational antitumoral therapy in the 30 days prior to beginning treatment
  • History of previous malignancy in the past 5 years, excepting basocellular or squamous cell skin cancer, or properly treated cervix cancer in situ
  • Woman with a positive pregnancy test in urine or serum during recruitment, prior to the administration of the study medication, or within 72 hours of beginning to take the study medication, or a woman who is nursing
  • WOCBP who does not wish to use or cannot use an effective contraceptive method to avoid pregnancy during the complete study period up to 4 weeks after ending the study.Male subjects also must agree to use an effective method of contraception.Note: WOCBP refers to any woman who has experienced menarche and has not undergone successful surgical sterilization or is not postmenopausal (defined as amenorrhea≥12 consecutive months,or women with hormonal replacement therapy and documented serum levels of follicle stimulating hormone).Even women who are using oral, implanted or injectable contraceptive hormones, mechanical products such as an intrauterine device or barrier methods to prevent pregnancy,or who practice abstinence or have a sterile partner, must be assumed to be WOCBP
  • Patient with any other condition or concurrent medical or psychiatric disease who,in opinion of the investigator, is not eligible to enter the study
  • Known hypersensitivity to any component of the study drug (XELOX/bevacizumab) or radiotherapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00909987

Locations
Spain
Hospital Clinic i Provincial de Barcelona Recruiting
Barcelona, Spain, 08036
Contact: Joan Maurel, Dr     932275400        
Principal Investigator: Joan Maurel, Oncologist            
Principal Investigator: Carles Conil, Radiotherapy            
Principal Investigator: Antonio Lacy, Surgeon            
Principal Investigator: Juan Ramón Ayuso, Radiologist            
Hospital Arnau de Vilanova Recruiting
Lérida, Spain, 25198
Contact: Antonieta Salud, Oncologist     973248100 / 973705200        
Principal Investigator: Antonieta Salud, Oncologist            
Principal Investigator: Moisés Miraflores, Radiotherapy            
Principal Investigator: Enrique Sierra Grañón, Surgeon            
Principal Investigator: Xavier matías-Guiu Guía, Pathologist            
Hospital La Paz Recruiting
Madrid, Spain, 28046
Contact: Jaime Feliu, Dr.     917277000        
Principal Investigator: Jaime Feliu, Oncologist            
Principal Investigator: María Elena Sánchez Santos, Radiotherapy            
Principal Investigator: Damián García Olmo, Surgeon            
Principal Investigator: Paula Alegría, Radiologist            
Hospital de Navarra Recruiting
Pamplona, Spain, 31008
Contact: Ruth Vera, Oncologist     848422100        
Principal Investigator: Ruth Vera, Oncologist            
Principal Investigator: Fernando Arias de la Vega, Radiotherapy            
Principal Investigator: Javier Suárez Alecha, Surgeon            
Principal Investigator: Javier Jiménez, Radiologist            
Principal Investigator: María Luisa Gómez, Pathologist            
Instituto Valenciano de Oncología (IVO) Recruiting
Valencia, Spain, 46009
Contact: Carlos Fernández Martos, Oncologist         cfmartos@fivo.org    
Principal Investigator: Carlos Fernández Martos, Oncologist            
Principal Investigator: José Luis Mengual, Radiotherapy            
Principal Investigator: Jorge Campos, Surgeon            
Principal Investigator: Jesús Santos, Radiologist            
Principal Investigator: Ana Calatrava, Pathologist            
Hospital La Fe Recruiting
Valencia, Spain, 46009
Contact: Jorge Aparicio, Dr.     963862700        
Principal Investigator: Jorge Aparicio, Oncologists            
Principal Investigator: Alejandro Tormo Micó, Radiotherapy            
Principal Investigator: Rafael Estevan, Surgeon            
Principal Investigator: Fernando Mas Estellés, Radiologist            
Principal Investigator: María José Artes, Pathologist            
Hospital General de Valencia Recruiting
Valencia, Spain, 46014
Contact: María José Safont     961972000        
Principal Investigator: María José Safont, Oncologist            
Principal Investigator: Ana Hernández Machancoses, Radiotherapy            
Principal Investigator: José Vicente Roig, Surgeon            
Principal Investigator: Vicente Martínez Sanjuán, Radiologist            
Principal Investigator: Encarna Martínez, Pathologist            
Hospital Miguel Servet Recruiting
Zaragoza, Spain, 50009
Contact: Vicente Alonso, Oncologist     976765500        
Principal Investigator: Vicente Alonso, Oncologist            
Principal Investigator: Martín Tejedor Gutierrez, Radiotherapy            
Principal Investigator: Andrés Monzón, Surgeon            
Principal Investigator: Luís Sarriá, Radiologist            
Principal Investigator: Carlos Hörndler, Pathologist            
Hospital Clínico Universitario Lozano Blesa Recruiting
Zaragoza, Spain, 50009
Contact: Pilar Escudero, Oncologist     976765700        
Principal Investigator: Pilar Escudero, Oncologist            
Principal Investigator: Javier Valencia, Radiotherapy            
Principal Investigator: Eloy Tejero, Surgeon            
Principal Investigator: José Antonio Fernández Gómez, Radiologist            
Principal Investigator: Javier Ortego, Pathologist            
Spain, Barcelona
Complejo Sanitario Parc Taulí Recruiting
Sabadell, Barcelona, Spain, 08208
Contact: Carles Pericay, Oncologist     937231010        
Principal Investigator: Carles Pericay, Oncologist            
Principal Investigator: Anna Darnell, Radiologist            
Principal Investigator: Alex Casalots Casado, Pathologist            
Sponsors and Collaborators
Grupo Espanol Multidisciplinario del Cancer Digestivo
Royal Marsden NHS Foundation Trust
Investigators
Study Chair: Carlos Fernández Martos, Oncologist Instituto Valenciano de Oncología (IVO)
Study Director: Carles Pericay, Oncologist Complejo Sanitario Parc Taulí
Principal Investigator: Antonieta Salud, Oncologist Hospital Arnau de Villanova (Lérida)
Principal Investigator: Vicente Alonso, Oncologist Hospital Miguel Servet
Principal Investigator: María José Safont, Oncologist Hospital General Universitario de Valencia
Principal Investigator: Ruth Vera, Oncologist Hospital de Navarra
Principal Investigator: Pilar Escudero, Oncologist Hospital Clínico Universitario Lozano Blesa
Principal Investigator: Joan Maurel, Oncologist Hospital Clinic i Provincial de Barcelona
Principal Investigator: Jorge Aparicio, Oncologist Hospital La Fe
Principal Investigator: Jaime Feliú, Oncologist Hospital La Paz
Principal Investigator: Mengual, Radiotherapy Instituto Valenciano de Oncología (IVO)
Principal Investigator: Moisés Miraflores, Radiotherapy Hospital Arnau de Vilanova (Lérida)
Principal Investigator: Martín Tejedor Gutierrez, Radiotherapy Hospital Miguel Servet
Principal Investigator: Ana Hernández Machancoses, Radiotherapy Hospital General Universitario de Valencia
Principal Investigator: Fernando Arias de la Vega, Radiotherapy Hospital de Navarra
Principal Investigator: Javier Valencia, Radiotherapy Hospital Clínico Universitario Lozano Blesa
Principal Investigator: Carles Conill, Radiotherapy Hospital Clinic i Provincial de Barcelona
Principal Investigator: Alejandro Tormo Micó, Radiotherapy Hospital La Fe
Principal Investigator: María Elena Sánchez Santos, Radiotherapy Hospital La Paz
Principal Investigator: Jorge Campos, Surgeon Instituto Valenciano de Oncología (IVO)
Principal Investigator: Enrique Sierra Grañón, Surgeon Hospital Arnau de Vilanova (Lérida)
Principal Investigator: Andrés Monzón, Surgeon Hospital Miguel Servet
Principal Investigator: José Vicente Roig, Surgeon Hospital General Universitario de Valencia
Principal Investigator: Javier Suárez Alecha, Surgeon Hospital de Navarra
Principal Investigator: Eloy Tejero, Surgeon Hospital Clínico Universitario Lozano Blesa
Principal Investigator: Antonio Lazy, Surgeon Hospital Clinic i Provincial de Barcelona
Study Director: Rafael Estevan, Surgeon Hospital La Fe
Principal Investigator: Damián García Olmo, Surgeon Hospital La Paz
Principal Investigator: Jesús Santos, Radiologist Instituto valenciano de Oncología (IVO)
Study Director: Ana Darnell, Radiologist Complejo Sanitario Parc Taulí
Principal Investigator: Luís Sarriá, Radiologist Hospital Miguel Servet
Principal Investigator: Vicente Martínez Sanjuán, Radiologist Hospital General Universitario de Valencia
Principal Investigator: Javier Jiménez, Radiologist Hospital de Navarra
Principal Investigator: José Antonio Fernández Gómez, Radiologist Hospital Clínico Universitario Lozano Blesa
Principal Investigator: Juan Ramón Ayuso, Radiologist Hospital Clinic i Provincial de Barcelona
Principal Investigator: Fernando Mas Estellés, Radiologist Hospital La Fe
Principal Investigator: Paula Alegría Hidalgo, Radiologist Hospital La Paz
Study Director: Anna Caltrava, Pathologist Instituto Valenciano de Oncología (IVO)
Principal Investigator: Alex Casalots, Pathologist Complejo Sanitario de Parc Taulí
Principal Investigator: Xavier Matias-Guiu Guia, Pathologist Hospital Arnau de Vilanova (Lérida)
Principal Investigator: Carlos Hörndler, Pathologist Hospital Miguel Servet
Principal Investigator: Encarna Martínez, Pathologist Hospital General Universitario de Valencia
Principal Investigator: María Luisa Gómez Dorronsoro, Pathologist Hospital de Navarra
Principal Investigator: Javier Ortego, Pathologist Hospital Clinico Universitario Lozano Blesa
Principal Investigator: María José Artes, Pathologist Hospital La Fe
  More Information

No publications provided

Responsible Party: GEMCAD ( Dr. Carlos Fernandez Martos )
Study ID Numbers: GEMCAD-0801
Study First Received: March 23, 2009
Last Updated: December 29, 2009
ClinicalTrials.gov Identifier: NCT00909987     History of Changes
Health Authority: Spain: Spanish Agency of Medicines

Keywords provided by Grupo Espanol Multidisciplinario del Cancer Digestivo:
rectum
intermediate risk cancer rectum
neoadjuvant

Additional relevant MeSH terms:
Antimetabolites
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Gastrointestinal Diseases
Rectal Neoplasms
Antineoplastic Agents
Physiological Effects of Drugs
Bevacizumab
Rectal Diseases
Oxaliplatin
Neoplasms by Site
Therapeutic Uses
Angiogenesis Modulating Agents
Growth Inhibitors
Capecitabine
Digestive System Neoplasms
Growth Substances
Intestinal Diseases
Angiogenesis Inhibitors
Intestinal Neoplasms
Pharmacologic Actions
Neoplasms
Digestive System Diseases
Gastrointestinal Neoplasms
Colorectal Neoplasms

ClinicalTrials.gov processed this record on February 08, 2010