Preoporative Bevacizumab, Radiation Therapy, and XELOX Chemotherapy for Locally Advanced Nonmetastatic Rectal Cancer

Sun Yat-sen University

Status and phase: Unknown; Phase 2

Conditions: Rectal Cancer

Treatments: Drug: Oxaliplatin; Procedure: surgery; Drug: Bevacizumab; Radiation: Radiation; Drug: Xeloda

Study type: Interventional

Funder types: Other

Identifiers

NCT01818973

6901061

Details and patient eligibility

About

We presumed that the addition of a monoclonal antibody Bevacizumab into radiation therapy and combination chemotherapy could results in improved pathologic tumor regression grade (TRG) in locally advanced nonmetastatic rectal cancer.

Full description

Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Giving bevacizumab together with radiation therapy and combination chemotherapy before surgery may achieve promising improvements in pCR rates, we designed this Phase II study in patients with T3/4 or N1/2 loco-regionally advanced rectum cancer, to examine the efficacy and safety of the addition of bevacizumab to a regimen of capecitabine and oxaliplatin in combination with pre-operative radiation.

Enrollment: 45 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically confirmed adenocarcinoma of the colon or rectum.
• T3 or T4 adenocarcinoma or node positive colorectal tumours.
• Appropriate staging investigations of the primary tumour, either endorectal ultrasound or pelvic MRI.
• Male or female aged 18 to 70.
• Have a performance status ECOG of 0 or 1.
• Have a life expectancy greater than 6 months.
• Adequate organ function and coagulation parameters as measured by: WBC > 4000/mm3, PLT > 100000/mm3, Hb > 10g/dL, ALT < 1.5X ULN, AST < 1.5X ULN, bilirubin < 1.5mg/dL Serum creatinine < 1.8mg/dL.
• Patient consent.

Exclusion criteria

• Known to have clinical or radiological evidence of distant metastases.
• Evidence of intestinal obstruction (except for those after enterostomy).
• Patients with a past history of colorectal surgery (except for enterostomy), chemtherapy, radiation, biotherapy or targeted therapy.
• Pregnant woman OR women of childbearing potential with a positive pregnancy test at baseline or lactating.
• Sexually active males and females (of childbearing potential) unwilling to practice contraception during the study.
• Patients with a past or current history (within last 5 years) of other malignancies, except for the indication under this study and curatively treated basal and squamous skin cancer or in-situ cancer of the cervix.
• Patients with mental disorder unable to complete the informed consent.
• Uncontrolled hypertension.
• Clinically significant (i.e. active) cardiovascular disease for example:

cerebrovascular accidents (<=6 months), myocardial infarction (<= 6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication.

• Moderate or serious proteinuria.
• Known hypersensitivity against experimental drugs.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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45 participants in 1 patient group

Single Arm

Experimental group

Description:

Neoadjuvant chemotherapy with XELOX: Xeloda, po, 1000mg/m2/12h daily, day 1 in the afternoon until day 15 in the morning; Oxaliplatin, iv, 130mg/m2, day 1; and Bevacizumab, iv, 7.5 mg/kg, day 1, during the first cycle (each cycle has 3 weeks). Followed by chemoradiotherapy, 50 Gy/25 fractions during 5 weeks plus 2 cycles XELOX and Bevacizumab: Xeloda, po, 1000mg/m2/12h daily, day 1 in the afternoon until day 15 in the morning; Oxaliplatin, iv, 100mg/m2, day 1; and Bevacizumab, iv, 7.5 mg/kg, day 1. 6-7 weeks from the last radiation therapy, Total Mesorectal Excision (TME) surgery will be performed. 3-4 weeks after operation, 3 cycles XELOX (the same as the neoadjuvant chemotherapy) and 2 cycles Xeloda (po, 1000mg/m2/12h daily, day 1 in the afternoon until day 15 in the morning) will be administered.

Treatment:

Drug: Oxaliplatin

Drug: Xeloda

Procedure: surgery

Drug: Bevacizumab

Radiation: Radiation