A Study of Avastin (Bevacizumab) Plus Xeloda (Capecitabine) in Patients With Locally Advanced Rectal Cancer.

Colorectal Cancer Clinical Trial

Official title:

An Open-label Study to Assess the Effect of Combination Treatment With Avastin and Xeloda, Plus Pre-operative Standard Radiotherapy, on Response Rate in Patients With Locally Advanced Rectal Cancer.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01227707
• Other study ID #: ML18522
• Status: Completed
• Phase: Phase 2
• First received: October 22, 2010
• Last updated: July 21, 2015
• Start date: November 2005
• Est. completion date: August 2010

Study information

• Verified date: July 2015
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

This open-label study will assess the efficacy and safety of Avastin (bevacizumab) plus Xeloda (capecitabine) in combination with standard technique radiotherapy of the pelvic region in the neo-adjuvant setting in patients with locally advanced primary rectal cancer. Patients will receive 4 courses of Avastin at a dose of 5 mg/kg intravenously (iv) every 2 weeks and for 38 days Xeloda at dose of 825 mg/kg twice daily orally, plus radiation therapy. After surgery, adjuvant treatment with 5-fluorouracil/leucovorin and, at the discretion of the investigator, with Avastin 5 mg/kg iv every 2 weeks for at least 6 months will be given.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 43
• Est. completion date: August 2010
• Est. primary completion date: August 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult patients, >=18 years of age

• Patients with confirmed rectal cancer who are subject to surgery and would benefit from pre-operative combined chemo-radiotherapy

• Measurable and/or evaluable lesions according to RECIST criteria

• EOCG performance status 0-1

Exclusion Criteria:

• Prior radiotherapy or chemotherapy for rectal cancer

• Untreated brain metastases or spinal cord compression or primary brain tumors

• Chronic daily treatment with high-dose aspirin (>325 mg/day) or other medications known to predispose to gastrointestinal ulceration

• Co-existing malignancies, or malignancies diagnosed within the last 5 years, with the exception of basal and squamous cell cancer, or cervical cancer in situ.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer

Intervention

Drug:
• bevacizumab [Avastin]
5 mg/kg intravenously every 2 weeks, 4 cycles
• capecitabine [Xeloda]
825 mg/m2 twice daily orally, 38 days

Radiation:
• Radiation therapy
Total dose of 45 Gy over 38 days

Procedure:
• Mesorectal excision
6-8 weeks after completion of neoadjuvant treatment

Drug:
• bevacizumab [Avastin]
Post-surgery adjuvant treatment at the discretion of the investigator: 5 mg/kg iv every 2 weeks for at least 6 months
• 5-fluorouracil
Post-surgery adjuvant therapy: bolus of 400mg/m2 iv plus iv infusion of 600 mg/m2 on Days 1 and 2 of each 2-week cycle for 6 months
• leucovorin
Post-surgery adjuvant treatment: 100 mg/m2 iv on Days 1 and 2 of each 2-week cycle for 6 months

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Pathological Complete Response (pCR)	pCR was defined as the absence of viable tumor cells, as determined by standard histologic procedure, in the tumor specimen (including regional lymph nodes) obtained at surgery. In order to minimize evaluation bias, tumor specimens were analyzed by both a central and local pathologist. The number of participants with pathological tumor stage 0 (pT0) and regional lymph nodes stage 0 (pN0) at surgery was determined. pCR was defined as the number of participants with pT0 and pN0 at surgery divided by the total number of participants with pathological tumor stage data collected.	6 to 8 weeks following completion of neoadjuvant treatment	No
Secondary	Percentage of Participants by Primary Tumor (T), Regional Lymph Nodes (N), and Distant Metastasis (M) Clinical Stage at Baseline and at the End of Neo-Adjuvant Treatment (NAT)	The frequencies of clinical tumor stage T (0, 1, 2, 3, 4, or X), regional lymph nodes stage N (0, 1, 2, 3, or 4), and distant metastasis clinical stage M (0, 1, or X) at baseline and at the end of NAT were assessed. The frequencies of pathological tumor stage T and regional lymph nodes stage N at surgery were evaluated. The clinical tumor and lymph node status was assessed by clinical examination, endosonography, and/or rectosigmoidoscopy, and pelvic and abdomen computerized tomography (CT) scan or magnetic resonance imaging (MRI). Response to treatment had to be assessed within 6 weeks after end of treatment by using the same techniques performed at baseline.	Baseline (BL) and end of neoadjuvant treatment (within 6 weeks after the completion of study treatment)	No
Secondary	Percentage of Participants Undergoing Sphincter-Saving Surgery by Type of Procedure		6 to 8 weeks after completion of study treatment	No
Secondary	Percentage of Participants With Complete Response (CR) at the End of Neoadjuvant Treatment	Percentage of participants with CR was evaluated as the proportion of participants with complete response for the target and non-target lesions, separately, at the end of NAT according to the Response Evaluation Criteria in Solid Tumors (RECIST). CR was defined as disappearance of all target lesions or all non-target lesions and normalization of tumor marker levels.	BL and within 6 weeks after the completion of study treatment	No
Secondary	Percentage of Participants With an Overall Response of CR at the End of Neoadjuvant Treatment	Percentage of participants with an overall response of CR was evaluated as the proportion of participants with CR for the target and non-target lesions plus absence of new lesions at the end of NAT according to RECIST. CR was defined as disappearance of all target lesions, all non-target lesions, and normalization of tumor marker levels.	BL and within 6 weeks after the completion of study treatment	No
Secondary	Percentage of Participants With New Lesions at the Primary Tumor Site at the End of Neoadjuvant Treatment	The percentage of participants with new lesions located at the primary tumor site were evaluated at the end of NAT.	BL and within 6 weeks after the completion of study treatment	No
Secondary	Percentage of Participants With Relapse During Follow-Up	The percentage of participants with local and/or regional relapse during follow-up. New lesions located at rectum or at colon or at lymph node detected at the end of NAT were evaluated as local and/or regional relapse.	BL, within 6 weeks after the completion of neoadjuvant treatment, every 2 weeks for 1 year following surgery, every 3 months thereafter until progression, up to 45 months	No
Secondary	Disease-Free Survival (DFS) - Percentage of Participants With an Event	DFS was defined as the time from treatment start date to the date of first progression of disease or date of death due to any cause.	BL, within 6 weeks after the completion of neoadjuvant treatment, every 2 weeks for 1 year following surgery, every 3 months thereafter until progression, up to 45 months	No
Secondary	DFS - Time to Event	The time in months from date of start-of-treatment to the date of event defined as the first documented disease progression or death due to any cause. If a participant did not have an event, the time was censored at the date of last adequate tumor assessment. DFS was estimated using the Kaplan-Meier method.	BL, within 6 weeks after the completion of neoadjuvant treatment, every 2 weeks for 1 year following surgery, every 3 months thereafter until progression, up to 45 months	No
Secondary	Overall Survival (OS) - Percentage of Participants With an Event	OS was defined as the time from the date of first day of treatment until death due to any cause or the last date the participant was known to be alive.	BL, within 6 weeks after the completion of neoadjuvant treatment, every 2 weeks for 1 year following surgery, every 3 months thereafter until death, up to 45 months	No
Secondary	OS - Time to Event	OS was defined as the time from the date of first day of treatment until death due to any cause or the last date the participant was known to be alive. OS was estimated using the Kaplan-Meier method.	BL, within 6 weeks after the completion of neoadjuvant treatment, every 2 weeks for 1 year following surgery, every 3 months thereafter until death, up to 45 months	No
Secondary	Time to Disease Progression (TTP) - Percentage of Participants With an Event	TTP was defined as the time from date of treatment start until first documented progression of disease or death due to underlying cancer.	BL, within 6 weeks after the completion of neoadjuvant treatment, every 2 weeks for 1 year following surgery, every 3 months thereafter until death, up to 45 months	No
Secondary	TTP - Time to Event	TTP was defined as the time from date of treatment start until first documented progression of disease or death due to underlying cancer. TTP was estimated using the Kaplan-Meier method.	BL, within 6 weeks after the completion of neoadjuvant treatment, every 2 weeks for 1 year following surgery, every 3 months thereafter until death, up to 45 months	No