Breast Cancer
Conditions
Keywords
Metastatic, HER2/neu+
Brief summary
This is a phase II study of the combination of oxaliplatin and trastuzumab as first or second line therapy in patients with stage IV, metastatic breast cancer
Detailed description
Eligible patients will receive a minimum of six cycles of combination therapy. If a patient is still responding to the oxaliplatin at 6 cycles, the oxaliplatin may be continued with the trastuzumab up to 10 cycles at the investigator's discretion. After discontinuing the oxaliplatin/trastuzumab combination, patients should continue with single agent trastuzumab until disease progression. Trastuzumab will be administered as an 8 mg/kg loading dose by intravenous (IV) infusion over 90 minutes on day 1 of cycle 1. Subsequent doses will be administered as a 6 mg/kg IV dose over 30 minutes. Oxaliplatin will be administered at a dose of 130 mg/ m2 over 120 minutes on day 1 of each cycle, following standard antiemetic premedications. 21 day cycles. For the first cycle, trastuzumab will be administered before oxaliplatin; however for subsequent cycles, oxaliplatin will be infused prior to trastuzumab
Interventions
DRUGTrastuzumab
Trastuzumab will be administered as an 8 mg/kg loading dose by intravenous (IV) infusion over 90 minutes on day 1 of cycle 1. Subsequent doses will be administered as a 6 mg/kg IV dose over 30 minutes.
DRUGOxaliplatin
Oxaliplatin will be administered at a dose of 130 mg/ m2 over 120 minutes on day 1 of each cycle, following standard antiemetic premedications. 21 day cycles. For the first cycle, trastuzumab will be administered before oxaliplatin; however for subsequent cycles, oxaliplatin will be infused prior to trastuzumab
Sponsors
Sanofi
SCRI Development Innovations, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Females ≥ 18 years of age * Histologically confirmed breast cancer that is HER2/neu positive (3+ by IHC or FISH +) and evidence of metastatic disease. Tumor may be of any estrogen and progesterone receptor type * Measurable disease by RECIST and an ECOG ≤ 2 * Patients with known evidence of brain metastases are eligible if they are asymptomatic and have completed all therapy (surgery, radiotherapy, and/or steroids) * Baseline LVEF value within the institutional normal range * Any number of prior hormonal therapy treatments in the adjuvant setting or for metastatic disease. A subject must have progressed on hormonal therapy and all hormonal therapy (including birth control pills) must be discontinued at study entry. * Prior chemotherapy in the adjuvant setting and up to one prior chemotherapy regimen for metastatic disease is allowed. * Patients may have received one prior trastuzumab/chemotherapy containing regimen or prior single agent trastuzumab. * Prior radiation therapy in the adjuvant setting or for metastatic disease, provided it was not to the only site of evaluable disease. * All prior chemotherapy, trastuzumab and radiation therapy should be completed \> 2 weeks before enrollment. * Patients receiving bisphosphonate therapy are eligible. However, if bisphosphonate were started within \< 2 months prior to enrollment, the bone lesions will not be evaluated for response and the patient must have another site of metastatic disease that is either measurable or evaluable for response. * Patients must have recovered from toxicities due to prior therapy. * Lab values in accordance with the protocol * Patients must be nonpregnant and nonlactating. Patients of childbearing potential must implement an effective method of contraception during the study (birth control pills are not allowed).
Exclusion criteria
* Bone only disease are ineligible * Patients who received more than 1 prior chemotherapy regimen for metastatic disease are ineligible. * Patients with a history of other cancers except curatively-treated carcinoma of the cervix in situ or non-melanomatous skin cancer. * Active serious infection or other underlying medical condition that would impair their ability to receive protocol treatment. * Uncontrolled nervous system metastases * Dementia or significantly altered mental status that would interfere with proper consenting. * Receiving other investigational therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment | 18 months | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression | 18 months | Time-to-progression was defined as the interval from first study treatment until the date that breast cancer progression was documented, other treatment was given, or death occurred. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Oxaliplatin/Trastuzumab Patients with HER2 positive breast cancer received treatment with oxaliplatin 130 mg/m2 IV day 1 and trastuzumab 6 mg/kg (following 8 mg/kg loading dose during cycle 1). Cycles were repeated every 21 days. Oxaliplatin : Oxaliplatin will be administered at a dose of 130 mg/ m2 over 120 minutes on day 1 of each cycle, following standard antiemetic premedications. 21 day cycles. For the first cycle, trastuzumab will be administered before oxaliplatin; however for subsequent cycles, oxaliplatin will be infused prior to trastuzumab Trastuzumab : Trastuzumab will be administered as an 8 mg/kg loading dose by intravenous (IV) infusion over 90 minutes on day 1 of cycle 1. Subsequent doses will be administered as a 6 mg/kg IV dose over 30 minutes. | 25 |
| Total | 25 |
Baseline characteristics
| Characteristic | Oxaliplatin/Trastuzumab |
|---|---|
| Age, Continuous | 59 years |
| Region of Enrollment United States | 25 participants |
| Sex: Female, Male Female | 25 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 20 / 25 |
| serious Total, serious adverse events | 7 / 25 |
Outcome results
Primary
Objective Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: 18 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oxaliplatin/Trastuzumab | Objective Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment | 20 percentage of participants |
Secondary
Time to Progression
Time-to-progression was defined as the interval from first study treatment until the date that breast cancer progression was documented, other treatment was given, or death occurred.
Time frame: 18 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Oxaliplatin/Trastuzumab | Time to Progression | 1.7 months |