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Study of Neoadjuvant CT With Selective Radiotherapy in Patients With Intermediate-Risk Cancer Rectum

This study has been completed.
Sponsor:
Collaborator:
Royal Marsden NHS Foundation Trust
Information provided by (Responsible Party):
Grupo Espanol Multidisciplinario del Cancer Digestivo
ClinicalTrials.gov Identifier:
NCT00909987
First received: March 23, 2009
Last updated: October 10, 2013
Last verified: September 2013
  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 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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 ]
  • Complete Phatologic Response (pCR) [ Time Frame: 2012 ] [ Designated as safety issue: No ]
    Complete pathologic response (pCR)estimated according to the number of subjects that showed yPT0N0 divided by the total number of subjects.


Enrollment: 46
Study Start Date: March 2009
Study Completion Date: June 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single arm

Neoadyuvant chemotherapy with XELOX: Xeloda 1000mg/m2/12h dayly, day one in the afternoon until day 15 in the morning; plus oxaliplatin 130mg/m2 (day 1); and Bevacizumab 7.5 mg/kg (day 1)during 3 cycles (each cycle of 3 weeks).

Followed by a selective use of chemoradiotherapy with radiotherapy (50.4Gy, 28 sesions of 1.8Gy during 5 weeks) plus Xeloda 825mg/m2/12h dayly.

Drug: Capecitabine
PO 1000 mg/m2 bid during day 1 to 15 for 3 cycles (every cycle has 3 weeks)
Other Name: Xeloda
Drug: Oxaliplatin
IV 130 mg/m2 during day 1 for 3 cycles (every cycle has 3 weeks)
Other Name: Oxaliplatin
Drug: Bevacizumab
IV 7.5 mg/Kg during 30 minutes day 1 during 4 cycles (every cycle has 3 weeks)
Other Name: Avastin
Radiation: Radiotherapy
Total dose 50.4 Gy administered during 28 days (1.8 Gy/day in 5 weeks).
Other Name: Neoadjuvant Radiotherapy
Drug: Capecitabine during all Radiotherapy period
825 mg/m2 bid
Other Name: Xeloda
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
Other Name: Total Mesorectal Excision (TME)

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
  • T3 tumor that meets all the following criteria in high-resolution magnetic resonance imaging (MRI) (3-mm slices) of the pelvis: distal border of tumor more than 5cm form the external edge of the anus and below the sacral promontory (located in the anatomy rectum).
  • 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00909987

Locations
Spain
Hospital General Universitario de Elche
Elche, Alicante, Spain, 03203
Complejo Sanitario Parc Taulí
Sabadell, Barcelona, Spain, 08208
Hospital del Mar
Barcelona, Spain, 08003
Hospital de La Santa Creu I Sant Pau
Barcelona, Spain, 08025
Hospital Clinic i Provincial de Barcelona
Barcelona, Spain, 08036
Hospital Arnau de Vilanova
Lérida, Spain, 25198
Hospital La Paz
Madrid, Spain, 28046
Hospital de Navarra
Pamplona, Spain, 31008
Hospital General de Valencia
Valencia, Spain, 46014
Hospital La Fe
Valencia, Spain, 46009
Instituto Valenciano de Oncología (IVO)
Valencia, Spain, 46009
Hospital Miguel Servet
Zaragoza, Spain, 50009
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
Principal Investigator: Marta Martín Richard, Oncologist Hospital Santa Creu i Sant Pau
Principal Investigator: Manuel Gallén, Oncologist Hospital del Mar
Principal Investigator: Javier Gallego, Oncologist Hospital General Universitario de Elche
  More Information

No publications provided by Grupo Espanol Multidisciplinario del Cancer Digestivo

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Grupo Espanol Multidisciplinario del Cancer Digestivo
ClinicalTrials.gov Identifier: NCT00909987     History of Changes
Other Study ID Numbers: GEMCAD-0801
Study First Received: March 23, 2009
Last Updated: October 10, 2013
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:
Bevacizumab
Capecitabine
Fluorouracil
Oxaliplatin
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014