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

NCT ID: NCT01818973

Last Updated: 2015-06-08

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-03-31
• Study Completion Date: 2020-03-31

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.

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.

Conditions

Rectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Xeloda

Intervention Type: DRUG

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

Oxaliplatin

Intervention Type: DRUG

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

Bevacizumab

Intervention Type: DRUG

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

Radiation

Intervention Type: RADIATION

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

surgery

Intervention Type: PROCEDURE

Total Mesorectal Excision (TME)

Interventions

Xeloda

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

Intervention Type: 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

Intervention Type: DRUG

Bevacizumab

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

Intervention Type: DRUG

Radiation

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

Intervention Type: RADIATION

surgery

Total Mesorectal Excision (TME)

Intervention Type: PROCEDURE

Other Intervention Names

Capecitabine; Avastin

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Yuan-hong Gao

Associate Professo

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Sun Yat-sen University Cancer Center (SYSUCC)

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Yuanhong Gao

Role: CONTACT

gaoyh@sysucc.org.cn

+86-20-87343385

Facility Contacts

Yuan-hong Gao

Role: primary

+86-20-87343385

References

Yu X, Wang QX, Xiao WW, Chang H, Zeng ZF, Lu ZH, Wu XJ, Chen G, Pan ZZ, Wan DS, Ding PR, Gao YH. Neoadjuvant oxaliplatin and capecitabine combined with bevacizumab plus radiotherapy for locally advanced rectal cancer: results of a single-institute phase II study. Cancer Commun (Lond). 2018 May 21;38(1):24. doi: 10.1186/s40880-018-0294-z.

Reference Type: DERIVED

PMID: 29784042 (View on PubMed)

Other Identifiers

6901061

Identifier Type: -

Identifier Source: org_study_id