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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Rectum Cancer

Intervention / Treatment
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* Drug: Capecitabine
* Drug: Oxaliplatin
* Drug: Bevacizumab
* Radiation: Radiotherapy
* Drug: Capecitabine during all Radiotherapy period
* Procedure: Total Mesorectal Excision (TME)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single arm<br>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<br>* PO 1000 mg/m2 bid during day 1 to 15 for 3 cycles (every cycle has 3 weeks)<br>* Other names: Xeloda;Drug: Oxaliplatin<br>* IV 130 mg/m2 during day 1 for 3 cycles (every cycle has 3 weeks)<br>Drug: Bevacizumab<br>* IV 7.5 mg/Kg during 30 minutes day 1 during 4 cycles (every cycle has 3 weeks)<br>* Other names: Avastin;Radiation: Radiotherapy<br>* Total dose 50.4 Gy administered during 28 days (1.8 Gy/day in 5 weeks).<br>* Other names: Neoadjuvant Radiotherapy;Drug: Capecitabine during all Radiotherapy period<br>* 825 mg/m2 bid<br>* Other names: Xeloda;Procedure: Total Mesorectal Excision (TME)<br>* 4 weeks from the last chemotherapy dose. In those patients who receive radiation TME wil be performed six weeks after<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rectum, intermediate risk cancer rectum, neoadjuvant