A Pilot Study of Neoadjuvant Chemotherapy Combined With Bevacizumab for Locally Advanced Rectal Cancer

Background: Neoadjuvant chemoradiotherapy (CRT) and total mesorectum excision (TME) has become the standard therapy for the treatment of locally advanced rectal cancer (LARC) to reduce the local recurrence rate, however, no improvement of distant metastasis rate was observed, and the incidence of postoperative local recurrence and distant metastasis can reach more than 25%. It is still a challenge for us to improve the RO resection rate of locally advanced rectal cancer and reduce the incidence of local recurrence and distant metastasis.

Study Overview

• Status: Unknown
• Conditions: Rectal Cancer
• Intervention / Treatment: Procedure: FOLFIRI+beacizumab; Procedure: CRT

Detailed Description

Objective: compared with the postoperative adjuvant therapy, neoadjuvant chemotherapy has shown better compliance of LARC patients, and may be more effective in reducing the incidence of local recurrence and distant metastasis. This study used the anti-angiogenesis drugs beacizumab and chemotherapy in patients with LARC for neoadjuvant chemotherapy, and investigated the short-term efficacy to provide objective basis for the selection of neoadjuvant therapy.

Methods: 70 patients with rectal adenocarcinoma clinical staging in Stage II or Stage III were included for neoadjuvant therapy followed by TME, of which 35 underwent neoadjuvant radiotherapy, and other 35 underwent neoadjuvant chemotherapy+beacizumab.

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100048
      • First Affiliated Hospital, Chinese PLA General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1. Clinical stage II or stage III rectal cancer patients diagnosed by preoperative biopsy pathology report, endoscopic examination report and preoperative abdominal pelvic dynamic contrast enhanced-MRI examination (DCE-MRI); 2. Primary tumor lesions within 4~12 cm from the anus through endoscopic examination; 3. No distant metastasis and intestinal obstruction; 4. No surgical contraindications; 5. Can be treated with neoadjuvant chemotherapy confirmed by normal routine examination; 6. informed consent with patients and family members before treatment.

Exclusion Criteria:

• history of beacizumab allergy, being treated with other therapy important viscera dysfunction and severe heart disease, including congestive heart failure, arrhythmia beyond the control, long-term drug treatment of angina pectoris, heart valve disease, myocardial infarction, and resistant hypertension; infectious wound and uncontrollable history of mental illness; infectious sexual diseases.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group; beacizumab+ neoadjuvant chemotherapy (FOLFIRI+beacizumab)	Procedure: FOLFIRI+beacizumab; Eligible patients received bevacizumab 5.0 mg/kg followed by irinotecan 125mg/m2 combined with LV 200mg/m2 followed by 5-FU bolus 400mg/m2,then 5-FU infusion 2.4~3.0g/m2 over a 46-h period.Those agents were given for a 2-week cycle.Treatment was administered for six cycles. LARC was reevaluated and operated after 4~8 weeks.
Active Comparator: Control group; neoadjuvant CRT for consecutive 5 weeks	Procedure: CRT; total dose of radiotherapy was 40~50Gy, a subdose of 1.8~2Gy for continuous 5 weeks, 5 times/week.Then,5-FU infusion 400mg/m2 combined with LV 200mg/m2 over 24 h for 4 days/week during the first and fifth weeks of radiotherapy.Whereas,Capecitabine was administered orally at a dose of 825mg/m2 twice a day for 5 days of a week. Second staging and operation were performed in the sixth week after chemoradiotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
R0 resection rate	percent	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
disease-free survival (DFS)	year	3 years
overall survival (OS)	year	3 years
overall response rate (ORR)	percent	3 years

Collaborators and Investigators

• Sponsor: Chinese PLA General Hospital
• Investigators: Principal Investigator: nan du, First Affiliated Hospital, Chinese PLA General Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): August 1, 2017
• Primary Completion (Anticipated): August 1, 2020
• Study Completion (Anticipated): August 1, 2020

Study Registration Dates

• First Submitted: August 1, 2017
• First Submitted That Met QC Criteria: August 7, 2017
• First Posted (Actual): August 10, 2017

Study Record Updates

• Last Update Posted (Actual): August 10, 2017
• Last Update Submitted That Met QC Criteria: August 7, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: neoadjuvant chemotherapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms
• Other Study ID Numbers: 20170801001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No