Locally Advanced Rectal Adenocarcinoma, Rectal Neoplasms
Conditions
Brief summary
The purpose of this study is to determine the pathological complete response rate of addition of bevacizumab to induction therapy (xelox) and concomitant treatment (capecitabine+radiotherapy), followed by surgery.
Interventions
DRUGbevacizumab
1. -Induction treatment. 4 cycles (every 3 weeks) of bevacizumab (7,5mg/kg day 1) + oxaliplatin (130mg/m2 day 1) + capecitabine (1000mg/m2/12h days 1-14) 2. -Concomitant (CT+RT) treatment (3 weeks later): bevacizumab (5mg/kg day 1 of 1st, 3th and 5th weeks) + capecitabine (825mg/m2/12h daily during radiotherapy treatment) + radiotherapy (45Gy (25fractions of 1,8Gy/day over 5weeks) followed by boost 5.4Gy (1,8Gy/day over 3days)) 3. -Surgery (6-8 weeks after last bevacizumab dose) 4. -Adjuvant treatment: It will be individual decision of each investigator, but it's recommended 4 cycles of XELOX (equal dose at induction treatment)
Sponsors
Hoffmann-La Roche
Associacio catalana per a la recerca oncologica i les seves implicacions sanitaries i socials
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Written informed consent from patients who are able to understand the study request * Histologically confirmed diagnosis of locally advanced rectal adenocarcinoma; ≤12 cm from the anal margin; T3, operable T4 or TxN+ * Karnofsky PS Index ≥ 70% * Life expectancy \> 6 months * Adequate bone marrow, liver and renal function: ANC ≥ 1.5 x 10e9/l; Platelets ≥ 100 x 10e9/l; Hb ≥ 9g/dl; INR ≤ 1.5; Bilirubin ≤ 1.5 x ULN; ALT and/or AST ≤ 2.5 x ULN or ≤ 5 x ULN (in case of hepatic metastasis); Alkaline phosphatase ≤ 2.5 x ULN or ≤ 5 x ULN (in case of hepatic metastasis) or ≤ 10 x ULN (in case of bone metastasis); Creatinine clearance (Cockcroft-Gault) ≥ 30 ml/min or seric creatinine ≤ 1.5 x ULN
Exclusion criteria
* Distant metastases; previous neoplasm during last 5 years or previous infiltrating neoplasm; previous treatment with radiotherapy or study drugs; recruited for other clinical trial in 4 weeks before study entry * Surgery, open biopsy or traumatic injury in 4 weeks before study entry; fine-needle aspiration in 7 days before study entry; major surgery planned during study * Previous heart disease or uncontrolled hypertension, previous hemorrhagic diathesis or coagulopathy; full-dose oral or parenteral anticoagulant or thrombolytic agent (low-dose warfarin is allowed, INR ≤ 1.5); chronic use of high-dose aspirin (\<325mg/day) or non-steroidal anti-inflammatory treatment * No integrity of the upper gastrointestinal tract, malabsorption syndrome or unable to take oral drugs * Pregnant or lactating patients; SNC disease; allogeneic transplant with immunosuppressive drugs; bone fracture not healed, wound or severe ulcers; uncontrolled intercurrent severe infections; previous related-fluoropyrimide SAEs or DPD deficiency
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pathologic Complete Response Rate | after concomitant CT-RT treatment |
Secondary
| Measure | Time frame |
|---|---|
| Disease Free Survival | from complete response to relapse or disease-related death |
| Time to Failure Treatment | from first treatment dose to drop out of the study |
| Complete Resection (R0) Rate | after surgery |
| Toxicity Evaluation | during study |
| Surgical Morbility | during surgery |
| Metastatic or Local Recurrence | during study |
Countries
Spain
Outcome results
None listed