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

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

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.

Study Overview

• Status: Completed
• Conditions: Rectum Cancer
• Intervention / Treatment: Drug: Capecitabine; Drug: Oxaliplatin; Drug: Bevacizumab; Radiation: Radiotherapy; Drug: Capecitabine during all Radiotherapy period; Procedure: 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.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08003
    • Hospital Del Mar
  • Barcelona, Spain, 08025
    • Hospital de la Santa Creu i Sant Pau
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial de Barcelona
  • Lérida, Spain, 25198
    • Hospital Arnau de Vilanova
  • Madrid, Spain, 28046
    • Hospital La Paz
  • Pamplona, Spain, 31008
    • Hospital de Navarra
  • Valencia, Spain, 46014
    • Hospital General de Valencia
  • Valencia, Spain, 46009
    • Hospital La Fe
  • Valencia, Spain, 46009
    • Instituto Valenciano de Oncología (IVO)
  • Zaragoza, Spain, 50009
    • Hospital Miguel Servet
  • Alicante
    • Elche, Alicante, Spain, 03203
      • Hospital General Universitario de Elche
  • Barcelona
    • Sabadell, Barcelona, Spain, 08208
      • Complejo Sanitario Parc Taulí

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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 Names: Xeloda; 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); Other Names: Avastin; Radiation: Radiotherapy; Total dose 50.4 Gy administered during 28 days (1.8 Gy/day in 5 weeks).; Other Names: Neoadjuvant Radiotherapy; Drug: Capecitabine during all Radiotherapy period; 825 mg/m2 bid; Other Names: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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	Until the end of study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Study treatment,which selectively omits neoadjuvant irradiation,can achieve a R0= 90%		At least 3 years for local recurrence and systemic recurrence
Rate of local and systemic recurrence		At least 3 years for local recurrence and systemic recurrence
Toxicity of treatment		At least 3 years for local recurrence and systemic recurrence
Rate of surgical complications during postoperative		At least 3 years for local recurrence and systemic recurrence
Profile of gene expression before neoadjuvant treatment		At least 3 years for local recurrence and systemic recurrence
Complete Phatologic Response (pCR)	Complete pathologic response (pCR)estimated according to the number of subjects that showed yPT0N0 divided by the total number of subjects.	2012

Collaborators and Investigators

• Sponsor: Grupo Espanol Multidisciplinario del Cancer Digestivo
• Collaborators: 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 Clínico 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

Publications and helpful links

General Publications

• Fernandez-Martos C, Brown G, Estevan R, Salud A, Montagut C, Maurel J, Safont MJ, Aparicio J, Feliu J, Vera R, Alonso V, Gallego J, Martin M, Pera M, Sierra E, Serra J, Delgado S, Roig JV, Santos J, Pericay C. Preoperative chemotherapy in patients with intermediate-risk rectal adenocarcinoma selected by high-resolution magnetic resonance imaging: the GEMCAD 0801 Phase II Multicenter Trial. Oncologist. 2014 Oct;19(10):1042-3. doi: 10.1634/theoncologist.2014-0233. Epub 2014 Sep 10.

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: March 23, 2009
• First Submitted That Met QC Criteria: May 28, 2009
• First Posted (Estimate): May 29, 2009

Study Record Updates

• Last Update Posted (Estimate): October 11, 2013
• Last Update Submitted That Met QC Criteria: October 10, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: neoadjuvant; rectum; intermediate risk cancer rectum
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Capecitabine; Oxaliplatin; Bevacizumab
• Other Study ID Numbers: GEMCAD-0801