Back to resultsA Study of Avastin (Bevacizumab) Plus Xeloda (Capecitabine) in Patients With Locally Advanced Rectal Cancer.
Primary Purpose
Colorectal Cancer
Status
Completed
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
bevacizumab [Avastin]
capecitabine [Xeloda]
Radiation therapy
Mesorectal excision
bevacizumab [Avastin]
5-fluorouracil
leucovorin
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer
Eligibility Criteria
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.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Single Arm
Arm Description
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Percentage of Participants Undergoing Sphincter-Saving Surgery by Type of Procedure
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01227707
Brief Title
A Study of Avastin (Bevacizumab) Plus Xeloda (Capecitabine) in Patients With Locally Advanced Rectal Cancer.
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.
Study Type
Interventional
2. Study Status
Record Verification Date
July 2015
Overall Recruitment Status
Completed
Study Start Date
November 2005 (undefined)
Primary Completion Date
August 2010 (Actual)
Study Completion Date
August 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
43 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Single Arm
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
bevacizumab [Avastin]
Intervention Description
5 mg/kg intravenously every 2 weeks, 4 cycles
Intervention Type
Drug
Intervention Name(s)
capecitabine [Xeloda]
Intervention Description
825 mg/m2 twice daily orally, 38 days
Intervention Type
Radiation
Intervention Name(s)
Radiation therapy
Intervention Description
Total dose of 45 Gy over 38 days
Intervention Type
Procedure
Intervention Name(s)
Mesorectal excision
Intervention Description
6-8 weeks after completion of neoadjuvant treatment
Intervention Type
Drug
Intervention Name(s)
bevacizumab [Avastin]
Intervention Description
Post-surgery adjuvant treatment at the discretion of the investigator: 5 mg/kg iv every 2 weeks for at least 6 months
Intervention Type
Drug
Intervention Name(s)
5-fluorouracil
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
leucovorin
Intervention Description
Post-surgery adjuvant treatment: 100 mg/m2 iv on Days 1 and 2 of each 2-week cycle for 6 months
Primary Outcome Measure Information:
Title
Percentage of Participants With Pathological Complete Response (pCR)
Description
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.
Time Frame
6 to 8 weeks following completion of neoadjuvant treatment
Secondary Outcome Measure Information:
Title
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)
Description
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.
Time Frame
Baseline (BL) and end of neoadjuvant treatment (within 6 weeks after the completion of study treatment)
Title
Percentage of Participants Undergoing Sphincter-Saving Surgery by Type of Procedure
Time Frame
6 to 8 weeks after completion of study treatment
Title
Percentage of Participants With Complete Response (CR) at the End of Neoadjuvant Treatment
Description
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.
Time Frame
BL and within 6 weeks after the completion of study treatment
Title
Percentage of Participants With an Overall Response of CR at the End of Neoadjuvant Treatment
Description
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.
Time Frame
BL and within 6 weeks after the completion of study treatment
Title
Percentage of Participants With New Lesions at the Primary Tumor Site at the End of Neoadjuvant Treatment
Description
The percentage of participants with new lesions located at the primary tumor site were evaluated at the end of NAT.
Time Frame
BL and within 6 weeks after the completion of study treatment
Title
Percentage of Participants With Relapse During Follow-Up
Description
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.
Time Frame
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
Title
Disease-Free Survival (DFS) - Percentage of Participants With an Event
Description
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.
Time Frame
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
Title
DFS - Time to Event
Description
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.
Time Frame
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
Title
Overall Survival (OS) - Percentage of Participants With an Event
Description
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.
Time Frame
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
Title
OS - Time to Event
Description
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.
Time Frame
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
Title
Time to Disease Progression (TTP) - Percentage of Participants With an Event
Description
TTP was defined as the time from date of treatment start until first documented progression of disease or death due to underlying cancer.
Time Frame
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
Title
TTP - Time to Event
Description
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.
Time Frame
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Chair
Facility Information:
City
Ancona
ZIP/Postal Code
60121
Country
Italy
City
Bologna
ZIP/Postal Code
40139
Country
Italy
City
Cuneo
ZIP/Postal Code
12100
Country
Italy
City
Genova
ZIP/Postal Code
16132
Country
Italy
City
Napoli
ZIP/Postal Code
80131
Country
Italy
City
Paola
ZIP/Postal Code
87027
Country
Italy
City
Pisa
ZIP/Postal Code
56100
Country
Italy
City
Roma
ZIP/Postal Code
00135
Country
Italy
City
Siena
ZIP/Postal Code
53100
Country
Italy
12. IPD Sharing Statement
Learn more about this trial
A Study of Avastin (Bevacizumab) Plus Xeloda (Capecitabine) in Patients With Locally Advanced Rectal Cancer.
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