XELOX+Bevacizumab Followed by Capecitabine+Bevacizumab+Radiotherapy as Neoadjuvant Treatment of Locally Advanced Rectal Adenocarcinoma

Associacio catalana per a la recerca oncologica i les seves implicacions sanitaries i socials

Status and phase: Unknown; Phase 2

Conditions: Locally Advanced Rectal Adenocarcinoma; Rectal Neoplasms

Treatments: Drug: bevacizumab

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00557713

AVACROSS

Details and patient eligibility

About

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.

Enrollment: 44 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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44 participants in 1 patient group

A

Experimental group

Description:

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)

Treatment:

Drug: bevacizumab