Colorectal Cancer
Conditions
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.
Interventions
DRUGbevacizumab [Avastin]
5 mg/kg intravenously every 2 weeks, 4 cycles
DRUGcapecitabine [Xeloda]
825 mg/m2 twice daily orally, 38 days
RADIATIONRadiation therapy
Total dose of 45 Gy over 38 days
PROCEDUREMesorectal excision
6-8 weeks after completion of neoadjuvant treatment
DRUG5-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
DRUGleucovorin
Post-surgery adjuvant treatment: 100 mg/m2 iv on Days 1 and 2 of each 2-week cycle for 6 months
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Pathological Complete Response (pCR) | 6 to 8 weeks following completion of neoadjuvant treatment | 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
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Undergoing Sphincter-Saving Surgery by Type of Procedure | 6 to 8 weeks after completion of study treatment | — |
| Percentage of Participants With Complete Response (CR) at the End of Neoadjuvant Treatment | BL and within 6 weeks after the completion of study 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 | BL and within 6 weeks after the completion of study 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 | BL and within 6 weeks after the completion of study 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 | 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 | 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. |
| 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) | Baseline (BL) and end of neoadjuvant treatment (within 6 weeks after the completion of study treatment) | 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. |
| DFS - Time to Event | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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. |
| Disease-Free Survival (DFS) - Percentage of Participants With an Event | 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 | 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. |
Countries
Italy
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bv+Capecitabine/Bv+Leucovorin+5-FU Participants received bevacizumab 5 mg/kg IV on Days -14, 1, 15, and 29 and capecitabine 825 mg/m\^2 PO BID from Days 1 to 38. Participants also received radiation therapy given at a daily fraction of 1.8 Gy administered in 5 weekly fractions starting at Week 1 (through Week 6) for a maximum total dose of 45 Gy. Six to 8 weeks following all above treatments, participants received complete mesorectal excision surgery. After surgery, participants received bevacizumab 5 mg/kg IV on Day 1 and leucovorin 100 mg/m\^2 IV (over 2 hours) followed by 5-FU 400 mg/m\^2 IV bolus and then 5-FU 600 mg/m\^2 IV (over 22 hours) on Days 1 and 2 every 2 weeks for a maximum of 12 cycles. | 43 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 10 |
| Overall Study | Death | 1 |
| Overall Study | Medical decision | 6 |
| Overall Study | Patient non-compliance | 3 |
| Overall Study | Progression of disease | 3 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Bv+Capecitabine/Bv+Leucovorin+5-FU |
|---|---|
| Age, Continuous | 61.49 years STANDARD_DEVIATION 10.85 |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 39 / 42 |
| serious Total, serious adverse events | 8 / 42 |
Outcome results
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.
Time frame: 6 to 8 weeks following completion of neoadjuvant treatment
Population: ITT population; only participants who underwent surgery and had pathological tumor stage data were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bv+Capecitabine/Bv+Leucovorin+5-FU | Percentage of Participants With Pathological Complete Response (pCR) | 10.00 percentage of participants |
p-value: 1one sample binomial test
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.
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
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bv+Capecitabine/Bv+Leucovorin+5-FU | DFS - Time to Event | 27.43 months | Standard Deviation 1.71 |
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.
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
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bv+Capecitabine/Bv+Leucovorin+5-FU | Disease-Free Survival (DFS) - Percentage of Participants With an Event | 30.23 percentage of participants |
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.
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
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bv+Capecitabine/Bv+Leucovorin+5-FU | OS - Time to Event | 32.14 months | Standard Deviation 1.46 |
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.
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
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bv+Capecitabine/Bv+Leucovorin+5-FU | Overall Survival (OS) - Percentage of Participants With an Event | 25.58 percentage of participants |
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.
Time frame: Baseline (BL) and end of neoadjuvant treatment (within 6 weeks after the completion of study treatment)
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bv+Capecitabine/Bv+Leucovorin+5-FU | 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) | End of NAT: T3, N2 | 2.33 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | 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) | Baseline: T3, NX | 2.33 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | 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) | End of NAT: T3, NX | 6.98 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | 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) | Baseline: T4, N3 | 2.33 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | 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) | Baseline: T0, N0 | 0 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | 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) | End of NAT: T0, N0 | 4.65 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | 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) | Baseline: T1, N0 | 0 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | 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) | End of NAT: T1, N0 | 4.65 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | 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) | Baseline: T1, NX | 0 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | 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) | End of NAT: T1, NX | 2.33 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | 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) | Baseline: T2, N0 | 0 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | 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) | End of NAT: T2, N0 | 18.60 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | 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) | Baseline: T2, N1 | 9.30 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | 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) | End of NAT: T2, N1 | 9.30 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | 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) | Baseline: T2, NX | 0 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | 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) | End of NAT: T2, NX | 6.98 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | 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) | Baseline: T3, N0 | 32.56 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | 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) | End of NAT: T3, N0 | 18.60 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | 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) | Baseline: T3, N1 | 46.51 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | 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) | End of NAT: T3, N1 | 9.30 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | 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) | Baseline: T3, N2 | 0 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | 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) | Baseline: T4, N0 | 0 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | 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) | End of NAT: T4, N0 | 4.65 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | 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) | Baseline: T4, N1 | 2.33 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | 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) | End of NAT: T4, N1 | 0 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | 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) | Baseline: T4, N2 | 2.33 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | 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) | End of NAT: T4, N2 | 0 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | 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) | End of NAT: T4, N3 | 0 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | 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) | Baseline: TX, N0 | 0 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | 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) | End of NAT: TX, N0 | 2.33 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | 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) | Baseline: TX, N2 | 2.33 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | 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) | End of NAT: TX, N2 | 0 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | 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) | Baseline: M0 | 97.67 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | 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) | End of NAT: M0 | 81.40 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | 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) | Baseline: M1 | 2.33 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | 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) | End of NAT: M1 | 2.33 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | 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) | Baseline: MX | 0 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | 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) | End of NAT: MX | 9.30 percentage of participants |
Secondary
Percentage of Participants Undergoing Sphincter-Saving Surgery by Type of Procedure
Time frame: 6 to 8 weeks after completion of study treatment
Population: ITT population; only participants who underwent surgery were included in the analysis. n (number) equals (=) number of participants assessed for the specified parameter (colostomy)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bv+Capecitabine/Bv+Leucovorin+5-FU | Percentage of Participants Undergoing Sphincter-Saving Surgery by Type of Procedure | Anterior resection | 70.0 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | Percentage of Participants Undergoing Sphincter-Saving Surgery by Type of Procedure | Abdomen-peritoneal amputation (Miles) | 22.5 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | Percentage of Participants Undergoing Sphincter-Saving Surgery by Type of Procedure | Other | 3.0 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | Percentage of Participants Undergoing Sphincter-Saving Surgery by Type of Procedure | Colostomy, temporary (n=32) | 47.50 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | Percentage of Participants Undergoing Sphincter-Saving Surgery by Type of Procedure | Colostomy, definitive (n=32) | 32.50 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | Percentage of Participants Undergoing Sphincter-Saving Surgery by Type of Procedure | No colostomy | 20.0 percentage of participants |
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.
Time frame: BL and within 6 weeks after the completion of study treatment
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bv+Capecitabine/Bv+Leucovorin+5-FU | Percentage of Participants With an Overall Response of CR at the End of Neoadjuvant Treatment | 9.30 percentage of participants |
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.
Time frame: BL and within 6 weeks after the completion of study treatment
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bv+Capecitabine/Bv+Leucovorin+5-FU | Percentage of Participants With Complete Response (CR) at the End of Neoadjuvant Treatment | CR of target lesion(s) | 11.63 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | Percentage of Participants With Complete Response (CR) at the End of Neoadjuvant Treatment | CR of non-target lesion(s) | 18.60 percentage of participants |
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.
Time frame: BL and within 6 weeks after the completion of study treatment
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bv+Capecitabine/Bv+Leucovorin+5-FU | Percentage of Participants With New Lesions at the Primary Tumor Site at the End of Neoadjuvant Treatment | 4.65 percentage of participants |
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.
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
Population: ITT population; only participants who underwent radical surgery were included in the analysis
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bv+Capecitabine/Bv+Leucovorin+5-FU | Percentage of Participants With Relapse During Follow-Up | No Relapse | 84.21 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | Percentage of Participants With Relapse During Follow-Up | 1 Relapse | 7.89 percentage of participants |
| Bv+Capecitabine/Bv+Leucovorin+5-FU | Percentage of Participants With Relapse During Follow-Up | 2 Relapses | 7.89 percentage of participants |
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.
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
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bv+Capecitabine/Bv+Leucovorin+5-FU | Time to Disease Progression (TTP) - Percentage of Participants With an Event | 27.91 percentage of participants |
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.
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
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bv+Capecitabine/Bv+Leucovorin+5-FU | TTP - Time to Event | 27.68 months | Standard Deviation 1.72 |