Clinical trial NCT00909987: Study of Neoadjuvant CT With Selective Radiotherapy in Patients With Intermediate-Risk Cancer Rectum
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rectum Cancer
Keywords: rectum
intermediate risk cancer rectum
neoadjuvant
Lead sponsor: Grupo Espanol Multidisciplinario del Cancer Digestivo
Sponsor class: OTHER
Collaborators: name: Royal Marsden NHS Foundation Trust
First posted: 2009-05-29
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: 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
timeFrame: Until the end of study
Secondary outcomes:
measure: Study treatment,which selectively omits neoadjuvant irradiation,can achieve a R0= 90%
timeFrame: At least 3 years for local recurrence and systemic recurrence
measure: Rate of local and systemic recurrence
timeFrame: At least 3 years for local recurrence and systemic recurrence
measure: Toxicity of treatment
timeFrame: At least 3 years for local recurrence and systemic recurrence
measure: Rate of surgical complications during postoperative
timeFrame: At least 3 years for local recurrence and systemic recurrence
measure: Profile of gene expression before neoadjuvant treatment
timeFrame: At least 3 years for local recurrence and systemic recurrence
measure: Complete Phatologic Response (pCR)
timeFrame: 2012
Other outcomes:
Locations:
city: Elche
country: Spain
facility: Hospital General Universitario de Elche
state: Alicante
city: Sabadell
country: Spain
facility: Complejo Sanitario Parc Taulí
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital de La Santa Creu I Sant Pau
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona
city: Lérida
country: Spain
facility: Hospital Arnau de Vilanova
city: Madrid
country: Spain
facility: Hospital La Paz
city: Pamplona
country: Spain
facility: Hospital de Navarra
city: Valencia
country: Spain
facility: Hospital La Fe
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncología (IVO)
city: Valencia
country: Spain
facility: Hospital General de Valencia
city: Zaragoza
country: Spain
facility: Hospital Miguel Servet
Study officials:
affiliation: Instituto Valenciano de Oncología (IVO)
name: Carlos Fernández Martos, Oncologist
role: STUDY_CHAIR
affiliation: Complejo Sanitario Parc Taulí
name: Carles Pericay, Oncologist
role: STUDY_DIRECTOR
affiliation: Hospital Arnau de Villanova (Lérida)
name: Antonieta Salud, Oncologist
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Miguel Servet
name: Vicente Alonso, Oncologist
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital General Universitario de Valencia
name: María José Safont, Oncologist
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital de Navarra
name: Ruth Vera, Oncologist
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Clínico Universitario Lozano Blesa
name: Pilar Escudero, Oncologist
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Clinic i provincial de Barcelona
name: Joan Maurel, Oncologist
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital La Fe
name: Jorge Aparicio, Oncologist
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital La Paz
name: Jaime Feliú, Oncologist
role: PRINCIPAL_INVESTIGATOR
affiliation: Instituto Valenciano de Oncología (IVO)
name: Mengual, Radiotherapy
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Arnau de Vilanova (Lérida)
name: Moisés Miraflores, Radiotherapy
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Miguel Servet
name: Martín Tejedor Gutierrez, Radiotherapy
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital General Universitario de Valencia
name: Ana Hernández Machancoses, Radiotherapy
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital de Navarra
name: Fernando Arias de la Vega, Radiotherapy
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Clínico Universitario Lozano Blesa
name: Javier Valencia, Radiotherapy
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Clinic i provincial de Barcelona
name: Carles Conill, Radiotherapy
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital La Fe
name: Alejandro Tormo Micó, Radiotherapy
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital La Paz
name: María Elena Sánchez Santos, Radiotherapy
role: PRINCIPAL_INVESTIGATOR
affiliation: Instituto Valenciano de Oncología (IVO)
name: Jorge Campos, Surgeon
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Arnau de Vilanova (Lérida)
name: Enrique Sierra Grañón, Surgeon
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Miguel Servet
name: Andrés Monzón, Surgeon
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital General Universitario de Valencia
name: José Vicente Roig, Surgeon
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital de Navarra
name: Javier Suárez Alecha, Surgeon
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Clínico Universitario Lozano Blesa
name: Eloy Tejero, Surgeon
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Clinic i provincial de Barcelona
name: Antonio Lazy, Surgeon
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital La Fe
name: Rafael Estevan, Surgeon
role: STUDY_DIRECTOR
affiliation: Hospital La Paz
name: Damián García Olmo, Surgeon
role: PRINCIPAL_INVESTIGATOR
affiliation: Instituto valenciano de Oncología (IVO)
name: Jesús Santos, Radiologist
role: PRINCIPAL_INVESTIGATOR
affiliation: Complejo Sanitario Parc Taulí
name: Ana Darnell, Radiologist
role: STUDY_DIRECTOR
affiliation: Hospital Miguel Servet
name: Luís Sarriá, Radiologist
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital General Universitario de Valencia
name: Vicente Martínez Sanjuán, Radiologist
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital de Navarra
name: Javier Jiménez, Radiologist
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Clínico Universitario Lozano Blesa
name: José Antonio Fernández Gómez, Radiologist
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Clinic i provincial de Barcelona
name: Juan Ramón Ayuso, Radiologist
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital La Fe
name: Fernando Mas Estellés, Radiologist
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital La Paz
name: Paula Alegría Hidalgo, Radiologist
role: PRINCIPAL_INVESTIGATOR
affiliation: Instituto Valenciano de Oncología (IVO)
name: Anna Caltrava, Pathologist
role: STUDY_DIRECTOR
affiliation: Complejo Sanitario de Parc Taulí
name: Alex Casalots, Pathologist
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Arnau de Vilanova (Lérida)
name: Xavier Matias-Guiu Guia, Pathologist
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Miguel Servet
name: Carlos Hörndler, Pathologist
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital General Universitario de Valencia
name: Encarna Martínez, Pathologist
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital de Navarra
name: María Luisa Gómez Dorronsoro, Pathologist
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Clinico Universitario Lozano Blesa
name: Javier Ortego, Pathologist
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital La Fe
name: María José Artes, Pathologist
role: PRINCIPAL_INVESTIGATOR
affiliation: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
name: Marta Martín Richard, Oncologist
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital del Mar
name: Manuel Gallén, Oncologist
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital General Universitario de Elche
name: Javier Gallego, Oncologist
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.