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

Rectum Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00909987
• Other study ID #: GEMCAD-0801
• Status: Completed
• Phase: Phase 2
• First received: March 23, 2009
• Last updated: October 10, 2013
• Start date: March 2009
• Est. completion date: June 2013

Study information

• Verified date: September 2013
• Source: Grupo Espanol Multidisciplinario del Cancer Digestivo
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: June 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Rectum Cancer

Intervention

Drug:
• Capecitabine
PO 1000 mg/m2 bid during day 1 to 15 for 3 cycles (every cycle has 3 weeks)
• Oxaliplatin
IV 130 mg/m2 during day 1 for 3 cycles (every cycle has 3 weeks)
• Bevacizumab
IV 7.5 mg/Kg during 30 minutes day 1 during 4 cycles (every cycle has 3 weeks)

Radiation:
• Radiotherapy
Total dose 50.4 Gy administered during 28 days (1.8 Gy/day in 5 weeks).

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

Locations

Country	Name	City	State
Spain	Hospital Clinic i Provincial de Barcelona	Barcelona
Spain	Hospital de La Santa Creu I Sant Pau	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital General Universitario de Elche	Elche	Alicante
Spain	Hospital Arnau de Vilanova	Lérida
Spain	Hospital La Paz	Madrid
Spain	Hospital de Navarra	Pamplona
Spain	Complejo Sanitario Parc Taulí	Sabadell	Barcelona
Spain	Hospital General de Valencia	Valencia
Spain	Hospital La Fe	Valencia
Spain	Instituto Valenciano de Oncología (IVO)	Valencia
Spain	Hospital Miguel Servet	Zaragoza

Sponsors (2)

Lead Sponsor	Collaborator
Grupo Espanol Multidisciplinario del Cancer Digestivo	Royal Marsden NHS Foundation Trust

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Study treatment,which selectively omits neoadjuvant irradiation,can achieve a R0= 90%		At least 3 years for local recurrence and systemic recurrence	Yes
Secondary	Rate of local and systemic recurrence		At least 3 years for local recurrence and systemic recurrence	Yes
Secondary	Toxicity of treatment		At least 3 years for local recurrence and systemic recurrence	Yes
Secondary	Rate of surgical complications during postoperative		At least 3 years for local recurrence and systemic recurrence	Yes
Secondary	Profile of gene expression before neoadjuvant treatment		At least 3 years for local recurrence and systemic recurrence	Yes
Secondary	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	No