Breast Cancer
Conditions
Brief summary
This single arm study will assess the efficacy and safety of Avastin in combination with Herceptin and Xeloda as first-line treatment of patients with HER2-positive locally recurrent or metastatic breast cancer. Patients will receive 3-weekly treatment cycles of Herceptin (8mg/kg iv on day 1 of first cycle, followed by 6mg/kg iv maintenance dose on day 1 of subsequent cycles), Xeloda (1000mg/m2 bid po on days 1-14 of each treatment cycle) and Avastin (15mg/kg on day 2 of first treatment cycle,and on day 1 of each subsequent cycle).The anticipated time on study treatment is until disease progression, and the target sample size is \<100 individuals.
Interventions
DRUGbevacizumab [Avastin]
15mg/kg iv on day 2 of first 3-week cycle,and on day 1 of subsequent cycles
DRUGcapecitabine [Xeloda]
1000mg/m2 bid po on days 1-14 of each 3-week cycle
8mg/kg iv loading dose on day 1 of first 3-week cycle, followed by 6mg/kg iv maintenance dose on day 1 of subsequent cycles
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
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; * breast cancer with measurable locally recurrent or metastatic lesions; * candidate for chemotherapy; * HER2-positive disease; * ECOG PS of \<=2.
Exclusion criteria
* previous anticancer therapy for metastatic breast cancer; * previous radiotherapy for metastatic breast cancer (except for adjuvant radiotherapy \>=6 months before enrollment); * chronic daily treatment with corticosteroids (\>=10mg/day), aspirin (\>325 mg/day) or clopidogrel (\>75mg/day); * other primary tumor within last 5 years, except for adequately treated cervical cancer in situ, squamous or basal cell skin cancer; * uncontrolled hypertension or significant cardiovascular disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Best Overall Response (BOR) of Confirmed Complete Response (CR) or Partial Response (PR) | Screening until disease progression (assessed at screening, every 6 weeks up to Week 36, thereafter every 9 weeks during treatment period, and then every 3 months during follow-up, up to approximately 4 years) | Tumor response was assessed using the Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.0. BOR was defined as the best response recorded for a participant from the start of treatment until disease progression/recurrence. Percentage of participants with a BOR of confirmed CR or PR (responders) was reported. CR: disappearance of all target and non-target lesions and normalization of tumor marker level; PR: at least a 30 percent (%) decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. Confirmed responses were those which were confirmed by a repeat assessment, performed 4 weeks after the criteria for response first met. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Screening until disease progression (assessed at screening, every 6 weeks up to Week 36, thereafter every 9 weeks during treatment period, and then every 3 months during follow-up, up to approximately 4 years) | PFS was defined as the time from enrollment to time of first documented disease progression or death due to any cause, whichever occurred first. Progression: at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. PFS was estimated using Kaplan-Meier methods. |
| Number of Participants With Overall Survival (OS) | Screening until death (assessed at screening, every 6 weeks up to Week 36, thereafter every 9 weeks during treatment period, and then every 3 months during follow-up, up to approximately 4 years) | OS was defined as the time from enrollment to death from any cause where enrollment was defined as successfully passed screening visit, enrolled in the study and received first dose of study treatment. |
| Overall Survival (OS) | Screening until death (assessed at screening, every 6 weeks up to Week 36, thereafter every 9 weeks during treatment period, and then every 3 months during follow-up, up to approximately 4 years) | OS was defined as the time from enrollment to death from any cause where enrollment was defined as successfully passed screening visit, enrolled in the study and received first dose of study treatment. OS was estimated using Kaplan-Meier methods. |
| Number of Participants With Disease Progression or Death | Screening until disease progression (assessed at screening, every 6 weeks up to Week 36, thereafter every 9 weeks during treatment period, and then every 3 months during follow-up, up to approximately 4 years) | Disease progression was defined as at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. |
| Time to Progression (TTP) | Screening until disease progression (assessed at screening, every 6 weeks up to Week 36, thereafter every 9 weeks during treatment period, and then every 3 months during follow-up, up to approximately 4 years) | TTP was defined as the time from enrollment to first documented disease progression (at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions). |
| Number of Participants With Response | Screening until disease progression (assessed at screening, every 6 weeks up to Week 36, thereafter every 9 weeks during treatment period, and then every 3 months during follow-up, up to approximately 4 years) | Participants who had CR or PR were considered as responders. CR: disappearance of all target and non-target lesions and normalization of tumor marker level; PR: at least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD. |
| Duration of Response (DR) | Screening until disease progression (assessed at screening, every 6 weeks up to Week 36, thereafter every 9 weeks during treatment period, and then every 3 months during follow-up, up to approximately 4 years) | DR was defined as the time from the first recorded response (CR/PR) to the date of first documented progression or death. CR: disappearance of all target lesions and non-target lesions and normalization of tumor marker level. PR: at least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD. Progression: at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. DR was estimated using Kaplan-Meier methods. |
| Number of Participants With Time to Progression (TTP) | Screening until disease progression (assessed at screening, every 6 weeks up to Week 36, thereafter every 9 weeks during treatment period, and then every 3 months during follow-up, up to approximately 4 years) | TTP was defined as the time from enrollment to first documented disease progression (at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions). TTP was estimated using Kaplan-Meier methods. |
Countries
Denmark, France, Russia, Slovakia, Spain, Sweden
Participant flow
Pre-assignment details
Screening details were taken 28 days prior to baseline. There were 88 participants included from 23 centers.
Participants by arm
| Arm | Count |
|---|---|
| Trastuzumab + Bevacizumab + Capecitabine Participants received IV trastuzumab (8 mg/kg) for first cycle and then 6 mg/kg for subsequent cycles followed by bevacizumab (15 mg/kg) on Day 1 of each treatment cycles along with capecitabine administered orally to participants at a dose of 1000 mg/m\^2 BID on Days 1 to 14 of each treatment cycle until disease progression, unmanageable toxicity or participant request for discontinuation. Treatment cycles were of 3 weeks. | 88 |
| Total | 88 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Administrative/Other Unspecified | 11 |
| Overall Study | Adverse Event/Intercurrent Illness | 8 |
| Overall Study | Death | 3 |
| Overall Study | Ongoing | 59 |
| Overall Study | Protocol Violation | 2 |
| Overall Study | Refused Treatment | 1 |
| Overall Study | Violation of Selection Criteria | 1 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Trastuzumab + Bevacizumab + Capecitabine |
|---|---|
| Age, Continuous | 53.0 years STANDARD_DEVIATION 10.94 |
| Sex: Female, Male Female | 87 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 81 / 88 |
| serious Total, serious adverse events | 20 / 88 |
Outcome results
Primary
Percentage of Participants With a Best Overall Response (BOR) of Confirmed Complete Response (CR) or Partial Response (PR)
Tumor response was assessed using the Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.0. BOR was defined as the best response recorded for a participant from the start of treatment until disease progression/recurrence. Percentage of participants with a BOR of confirmed CR or PR (responders) was reported. CR: disappearance of all target and non-target lesions and normalization of tumor marker level; PR: at least a 30 percent (%) decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. Confirmed responses were those which were confirmed by a repeat assessment, performed 4 weeks after the criteria for response first met.
Time frame: Screening until disease progression (assessed at screening, every 6 weeks up to Week 36, thereafter every 9 weeks during treatment period, and then every 3 months during follow-up, up to approximately 4 years)
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab + Bevacizumab + Capecitabine | Percentage of Participants With a Best Overall Response (BOR) of Confirmed Complete Response (CR) or Partial Response (PR) | 75.0 percentage of participants |
Secondary
Duration of Response (DR)
DR was defined as the time from the first recorded response (CR/PR) to the date of first documented progression or death. CR: disappearance of all target lesions and non-target lesions and normalization of tumor marker level. PR: at least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD. Progression: at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. DR was estimated using Kaplan-Meier methods.
Time frame: Screening until disease progression (assessed at screening, every 6 weeks up to Week 36, thereafter every 9 weeks during treatment period, and then every 3 months during follow-up, up to approximately 4 years)
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab + Bevacizumab + Capecitabine | Duration of Response (DR) | 12.7 months |
Secondary
Number of Participants With Disease Progression or Death
Disease progression was defined as at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Time frame: Screening until disease progression (assessed at screening, every 6 weeks up to Week 36, thereafter every 9 weeks during treatment period, and then every 3 months during follow-up, up to approximately 4 years)
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab + Bevacizumab + Capecitabine | Number of Participants With Disease Progression or Death | 70 participants |
Secondary
Number of Participants With Overall Survival (OS)
OS was defined as the time from enrollment to death from any cause where enrollment was defined as successfully passed screening visit, enrolled in the study and received first dose of study treatment.
Time frame: Screening until death (assessed at screening, every 6 weeks up to Week 36, thereafter every 9 weeks during treatment period, and then every 3 months during follow-up, up to approximately 4 years)
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab + Bevacizumab + Capecitabine | Number of Participants With Overall Survival (OS) | 40 participants |
Secondary
Number of Participants With Response
Participants who had CR or PR were considered as responders. CR: disappearance of all target and non-target lesions and normalization of tumor marker level; PR: at least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD.
Time frame: Screening until disease progression (assessed at screening, every 6 weeks up to Week 36, thereafter every 9 weeks during treatment period, and then every 3 months during follow-up, up to approximately 4 years)
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab + Bevacizumab + Capecitabine | Number of Participants With Response | 66 participants |
Secondary
Number of Participants With Time to Progression (TTP)
TTP was defined as the time from enrollment to first documented disease progression (at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions). TTP was estimated using Kaplan-Meier methods.
Time frame: Screening until disease progression (assessed at screening, every 6 weeks up to Week 36, thereafter every 9 weeks during treatment period, and then every 3 months during follow-up, up to approximately 4 years)
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab + Bevacizumab + Capecitabine | Number of Participants With Time to Progression (TTP) | 62 participants |
Secondary
Overall Survival (OS)
OS was defined as the time from enrollment to death from any cause where enrollment was defined as successfully passed screening visit, enrolled in the study and received first dose of study treatment. OS was estimated using Kaplan-Meier methods.
Time frame: Screening until death (assessed at screening, every 6 weeks up to Week 36, thereafter every 9 weeks during treatment period, and then every 3 months during follow-up, up to approximately 4 years)
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab + Bevacizumab + Capecitabine | Overall Survival (OS) | 31.8 months |
Secondary
Progression Free Survival (PFS)
PFS was defined as the time from enrollment to time of first documented disease progression or death due to any cause, whichever occurred first. Progression: at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. PFS was estimated using Kaplan-Meier methods.
Time frame: Screening until disease progression (assessed at screening, every 6 weeks up to Week 36, thereafter every 9 weeks during treatment period, and then every 3 months during follow-up, up to approximately 4 years)
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab + Bevacizumab + Capecitabine | Progression Free Survival (PFS) | 14.2 months |
Secondary
Time to Progression (TTP)
TTP was defined as the time from enrollment to first documented disease progression (at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions).
Time frame: Screening until disease progression (assessed at screening, every 6 weeks up to Week 36, thereafter every 9 weeks during treatment period, and then every 3 months during follow-up, up to approximately 4 years)
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab + Bevacizumab + Capecitabine | Time to Progression (TTP) | 14.5 months |