Breast Cancer
Conditions
Keywords
Breast cancer
Brief summary
The aim of this international open-label randomized phase II trial is to evaluate the efficacy and safety of an all-oral combination and two all-intravenous combinations as first-line therapy for HER2-negative mBC patients.
Interventions
DRUGoral vinorelbine
Oral vinorelbine 60 mg/m² on day 1 & day 8, for cycle 1, and then 80 mg/m² on day 1 & day 8, every 3 weeks for subsequent cycles
DRUGCapecitabine
Capecitabine 1000 mg/m² twice a day (2000 mg/m² daily) from day 1 to day 14
DRUGGemcitabine 1250 mg/m²
Gemcitabine 1250 mg/m² on day 1 & day 8
DRUGGemcitabine 1000 mg/m²
Gemcitabine: 1000 mg/m² on day 1 & 8
DRUGPaclitaxel
Paclitaxel 175 mg/m² on day 1
DRUGDocetaxel
Docetaxel 75 mg/m² on day 1
Sponsors
Pierre Fabre Medicament
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
* Histologically confirmed adenocarcinoma of the breast; * Documented metastatic disease previously untreated by chemotherapy; * HER2 negative (assessed by 0-1+ IHC or 2+ IHC with FISH-) on the primary tumor or on metastatic site; * Karnofsky Performance Status 70%.
Exclusion criteria
* Local relapse alone after conservative treatment or contra-lateral tumor; * Patients with symptoms suggesting CNS involvement or leptomeningeal metastases; * Concomitant hormonal therapy for metastatic breast cancer; * Prior chemotherapy in the metastatic setting; * Patients previously treated with a vinca-alkaloid, capecitabine, gemcitabine or taxanes; * Prior severe and unexpected reaction to fluoropyrimidine therapy (with or without documented DPD deficiency) or known hypersensitivity to 5-fluorouracil.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (DCR) | From Baseline to disease progression or death, up to 6 years | Disease control rate (DCR) defined as the sum of complete response, partial response and stable disease for at least 3 months according to RECIST criteria version 1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR)= Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions. Stable disease: no partial response or progression of the disease |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Vinorelbine-Capecitabine (Arm A) oral vinorelbine (OV) with capecitabine (CAP)
oral vinorelbine: Oral vinorelbine 60 mg/m² on day 1 & day 8, for cycle 1, and then 80 mg/m² on day 1 & day 8, every 3 weeks for subsequent cycles
Capecitabine: Capecitabine 1000 mg/m² twice a day (2000 mg/m² daily) from day 1 to day 14 | 49 |
| Gemcitabine-Paclitaxel (Arm B) gemcitabine (GEM) in combination with paclitaxel (PAC)
Gemcitabine 1250 mg/m²: Gemcitabine 1250 mg/m² on day 1 & day 8
Paclitaxel: Paclitaxel 175 mg/m² on day 1 | 50 |
| Gemcitabine-Docetaxel (Arm C) gemcitabine (GEM) in combination with docetaxel (DOC)
Gemcitabine 1000 mg/m²: Gemcitabine: 1000 mg/m² on day 1 & 8
Docetaxel: Docetaxel 75 mg/m² on day 1 | 50 |
| Total | 149 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 2 | 2 | 1 |
| Overall Study | Drug related toxicity | 7 | 7 | 13 |
| Overall Study | Non drug related toxicity | 3 | 0 | 0 |
| Overall Study | other reason | 6 | 20 | 17 |
| Overall Study | Progressive disease | 23 | 14 | 7 |
| Overall Study | Protocol Violation | 3 | 1 | 2 |
| Overall Study | Withdrawal by Subject | 7 | 6 | 11 |
Baseline characteristics
| Characteristic | Vinorelbine-Capecitabine (Arm A) | Gemcitabine-Paclitaxel (Arm B) | Gemcitabine-Docetaxel (Arm C) | Total |
|---|---|---|---|---|
| Age, Continuous | 56.4 years STANDARD_DEVIATION 9.7 | 56.0 years STANDARD_DEVIATION 10.8 | 57.4 years STANDARD_DEVIATION 9.7 | 56.6 years STANDARD_DEVIATION 10 |
| Body surface area | 1.8 mg/m² STANDARD_DEVIATION 0.2 | 1.7 mg/m² STANDARD_DEVIATION 0.2 | 1.8 mg/m² STANDARD_DEVIATION 0.2 | 1.7 mg/m² STANDARD_DEVIATION 0.2 |
| Categorized number of organs involved at baseline 1 organ | 9 Participants | 3 Participants | 4 Participants | 16 Participants |
| Categorized number of organs involved at baseline 2 organs | 14 Participants | 25 Participants | 17 Participants | 56 Participants |
| Categorized number of organs involved at baseline >= 3 organs | 26 Participants | 22 Participants | 29 Participants | 77 Participants |
| Delay between diagnosis and study entry | 5.5 years STANDARD_DEVIATION 5.7 | 5.8 years STANDARD_DEVIATION 6.3 | 5.8 years STANDARD_DEVIATION 5.9 | 5.7 years STANDARD_DEVIATION 5.9 |
| Delay between first relapse/progression and study entry | 8.8 months STANDARD_DEVIATION 19.1 | 11.1 months STANDARD_DEVIATION 29.8 | 11.3 months STANDARD_DEVIATION 23.9 | 10.4 months STANDARD_DEVIATION 24.5 |
| Primary tumour site Bilateral | 3 Participants | 0 Participants | 0 Participants | 3 Participants |
| Primary tumour site Left breast | 20 Participants | 24 Participants | 29 Participants | 73 Participants |
| Primary tumour site Right breast | 26 Participants | 26 Participants | 21 Participants | 73 Participants |
| Sex: Female, Male Female | 49 Participants | 50 Participants | 50 Participants | 149 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 31 / 49 | 37 / 50 | 35 / 50 |
| other Total, other adverse events | 49 / 49 | 50 / 50 | 50 / 50 |
| serious Total, serious adverse events | 13 / 49 | 16 / 50 | 12 / 50 |
Outcome results
Primary
Disease Control Rate (DCR)
Disease control rate (DCR) defined as the sum of complete response, partial response and stable disease for at least 3 months according to RECIST criteria version 1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR)= Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions. Stable disease: no partial response or progression of the disease
Time frame: From Baseline to disease progression or death, up to 6 years
Population: Disease control rate was measured in the Intent-to-treat ITT population that consisted of all treated patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vinorelbine-Capecitabine (Arm A) | Disease Control Rate (DCR) | 73.5 percentage of participants |
| Gemcitabine-Paclitaxel (Arm B) | Disease Control Rate (DCR) | 78.0 percentage of participants |
| Gemcitabine-Docetaxel (Arm C) | Disease Control Rate (DCR) | 80.0 percentage of participants |