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

Sponsor

Sun Yat-sen University (Other)

Overall Status

Unknown status

CT.gov ID

NCT01818973

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Rectal Cancer	Drug: Xeloda Drug: Oxaliplatin Drug: Bevacizumab Radiation: Radiation Procedure: surgery	Phase 2

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

45 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Study Start Date :

Mar 1, 2013

Anticipated Primary Completion Date :

Jun 1, 2015

Anticipated Study Completion Date :

Mar 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single Arm 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.	Drug: Xeloda po, 1000mg/m2/12h daily, day 1 in the afternoon until day 15 in the morning, 8 cycles Other Names: Capecitabine Drug: Oxaliplatin iv, 130mg/m2, day 1, 1 cycle during neoadjuvant chemotherapy and 3 cycles in adjuvant chemotherapy 100mg/m2, day 1, 2 cycles during concurrent chemoradiotherapy Drug: Bevacizumab iv, 7.5 mg/kg, day 1, 3 cycles during neoadjuvant chemotherapy and concurrent chemoradiotherapy Other Names: Avastin Radiation: Radiation Intensity-modulated radiation therapy, 50 Gy/25 fractions during 5 weeks Procedure: surgery Total Mesorectal Excision (TME)

Arm

Intervention/Treatment

Experimental: Single Arm

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.

Drug: Xeloda

po, 1000mg/m2/12h daily, day 1 in the afternoon until day 15 in the morning, 8 cycles

Other Names:

Capecitabine

Drug: Oxaliplatin

iv, 130mg/m2, day 1, 1 cycle during neoadjuvant chemotherapy and 3 cycles in adjuvant chemotherapy 100mg/m2, day 1, 2 cycles during concurrent chemoradiotherapy

Drug: Bevacizumab

iv, 7.5 mg/kg, day 1, 3 cycles during neoadjuvant chemotherapy and concurrent chemoradiotherapy

Other Names:

Avastin

Radiation: Radiation

Intensity-modulated radiation therapy, 50 Gy/25 fractions during 5 weeks

Procedure: surgery

Total Mesorectal Excision (TME)

Outcome Measures

Primary Outcome Measures

The pathologic tumor regression grade (TRG) [March 30, 2015]

Secondary Outcome Measures

5-y overall survival [March 30, 2020]
Occurence of toxicity [March 30, 2015]
5-y local relapse free survival [March 30, 2020]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts 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.