Colorectal Cancer
Conditions
Brief summary
This 2-arm study evaluated the efficacy and safety of 2 different treatment schedules of oral Xeloda with intravenous (IV) Eloxatin (oxaliplatin) and IV bevacizumab (Avastin) as a first-line treatment in patients with locally advanced or metastatic colorectal cancer. Patients were randomized to receive either: 1) Xeloda 850 mg/m\^2 orally twice a day (po bid) on Days 1-14, oxaliplatin 130 mg/m\^2 IV on Day 1, and Avastin 7.5 mg/kg IV on Day 1 of each 3-week cycle; or 2) Xeloda 1500 mg/m\^2 po bid on Days 1-7, oxaliplatin 85 mg/m\^2 IV on Day 1 and Avastin 5 mg/kg IV on Day 1 of each 2-week cycle. The anticipated time on study treatment was 1-2 years, and the target sample size was 100-500 individuals.
Interventions
DRUGcapecitabine
850 mg/m\^2 po bid on Days 1-14 of each 3-week cycle
DRUGOxaliplatin
130 mg/m\^2 IV on Day 1 of each 3-week cycle
DRUGbevacizumab
7.5 mg/kg IV on Day 1 of each 3-week cycle
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Metastatic or inoperable locally advanced colorectal cancer * \>=1 measurable target lesion
Exclusion criteria
* Previous systemic therapy for advanced or metastatic disease * Previous treatment with bevacizumab
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | Time to disease progression or death (through follow-up phase) | Progression-free survival was defined as the time from the date of randomization to the first occurrence of having documented disease progression or death due to any cause, whichever comes first. Progression was based on tumor assessments made by the investigators according to Response Evaluation Criteria in Solid Tumors (RECIST). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Time to death (through follow-up phase): Approximate Median of 718 days | Overall survival was defined as the time from the date of randomization to the date of death, for any cause. |
| Best Overall Clinical Response | Through follow-up phase: Approximate Median of 318 days | Overall response rate was assessed according to RECIST (the best response recorded from the time of randomization to the first CR or PR. The patient's overall best response was complete response (CR), partial response (PR) (CR and PR considered responders), stable disease (SD), or progressive disease (PD). To be assigned a status of complete response (CR) or partial response (PR), changes in tumor measurements were confirmed by repeat assessments performed no less than 4 weeks after the criteria for response were first met. |
| Duration of Overall Clinical Response (CR or PR) | Time to Disease Progression or Death (through follow-up phase): Approximate Median of 302 days | Among tumor responders (i.e., patients with overall best response of CR or PR), duration of overall response was measured from the time criteria were first met for CR or PR (whichever status was recorded first) to the date of either recurrent/progressive disease was objectively documented or death from any cause. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| XELOX Q3W + Bevacizumab Capecitabine 850 mg/m\^2 twice-daily was given orally. Bevacizumab 7.5 mg/kg via 30-90 minute intravenous (IV) infusion was administered on day 1 every three weeks prior to administration of oxaliplatin.
Oxaliplatin 130 mg/m\^2 via 2-hour IV infusion was administered on day 1 every 3 weeks. | 217 |
| XELOX Q2W + Bevacizumab Capecitabine 1500 mg/m\^2 twice-daily was given orally. Bevacizumab 5 mg/kg via 30-90 minute intravenous (IV) infusion was administered on day 1 every two weeks prior to administration of oxaliplatin.
Oxaliplatin 85 mg/m\^2 via 2-hour IV infusion was administered on day 1 every 2 weeks. | 218 |
| Total | 435 |
Baseline characteristics
| Characteristic | XELOX Q3W + Bevacizumab | XELOX Q2W + Bevacizumab | Total |
|---|---|---|---|
| Age Continuous | 60.6 years STANDARD_DEVIATION 11.45 | 60.8 years STANDARD_DEVIATION 12.17 | 60.7 years STANDARD_DEVIATION 11.81 |
| Sex: Female, Male Female | 89 Participants | 96 Participants | 185 Participants |
| Sex: Female, Male Male | 128 Participants | 122 Participants | 250 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 202 / 208 | 206 / 211 |
| serious Total, serious adverse events | 84 / 208 | 94 / 211 |
Outcome results
Primary
Progression-free Survival (PFS)
Progression-free survival was defined as the time from the date of randomization to the first occurrence of having documented disease progression or death due to any cause, whichever comes first. Progression was based on tumor assessments made by the investigators according to Response Evaluation Criteria in Solid Tumors (RECIST).
Time frame: Time to disease progression or death (through follow-up phase)
Population: Intent-to-treat population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| XELOX Q3W + Bevacizumab | Progression-free Survival (PFS) | 287 Days |
| XELOX Q2W + Bevacizumab | Progression-free Survival (PFS) | 273 Days |
p-value: 0.388395% CI: [0.67, 1.17]Log Rank
Secondary
Best Overall Clinical Response
Overall response rate was assessed according to RECIST (the best response recorded from the time of randomization to the first CR or PR. The patient's overall best response was complete response (CR), partial response (PR) (CR and PR considered responders), stable disease (SD), or progressive disease (PD). To be assigned a status of complete response (CR) or partial response (PR), changes in tumor measurements were confirmed by repeat assessments performed no less than 4 weeks after the criteria for response were first met.
Time frame: Through follow-up phase: Approximate Median of 318 days
Population: Intent-to-treat population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| XELOX Q3W + Bevacizumab | Best Overall Clinical Response | Responders (with CR or PR) | 72 Patients |
| XELOX Q3W + Bevacizumab | Best Overall Clinical Response | Partial Response (PR) | 70 Patients |
| XELOX Q3W + Bevacizumab | Best Overall Clinical Response | Complete Response (CR) | 2 Patients |
| XELOX Q3W + Bevacizumab | Best Overall Clinical Response | Nonresponders (without CR or PR) | 145 Patients |
| XELOX Q2W + Bevacizumab | Best Overall Clinical Response | Complete Response (CR) | 3 Patients |
| XELOX Q2W + Bevacizumab | Best Overall Clinical Response | Responders (with CR or PR) | 51 Patients |
| XELOX Q2W + Bevacizumab | Best Overall Clinical Response | Nonresponders (without CR or PR) | 167 Patients |
| XELOX Q2W + Bevacizumab | Best Overall Clinical Response | Partial Response (PR) | 48 Patients |
95% CI: [0.9, 18.7]
Secondary
Duration of Overall Clinical Response (CR or PR)
Among tumor responders (i.e., patients with overall best response of CR or PR), duration of overall response was measured from the time criteria were first met for CR or PR (whichever status was recorded first) to the date of either recurrent/progressive disease was objectively documented or death from any cause.
Time frame: Time to Disease Progression or Death (through follow-up phase): Approximate Median of 302 days
Population: Intent-to-treat population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| XELOX Q3W + Bevacizumab | Duration of Overall Clinical Response (CR or PR) | 281 Days to event |
| XELOX Q2W + Bevacizumab | Duration of Overall Clinical Response (CR or PR) | 316 Days to event |
p-value: 0.629495% CI: [0.66, 1.97]Log Rank
Secondary
Overall Survival
Overall survival was defined as the time from the date of randomization to the date of death, for any cause.
Time frame: Time to death (through follow-up phase): Approximate Median of 718 days
Population: Intent-to-treat population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| XELOX Q3W + Bevacizumab | Overall Survival | 852 Days |
| XELOX Q2W + Bevacizumab | Overall Survival | 662 Days |
p-value: 0.245895% CI: [0.64, 1.12]Log Rank