Clinical Trial Result Information
Title of Study:
A phase II trial evaluating the administration of trastuzumab in combination with cisplatin-epirubicin-paclitaxel (PETH) in metastatic breast cancer patients.
Fast Facts:
| Protocol number: | M77050 |
| Sponsor: | Roche S.p.A. Italy |
| Company division: | Pharmaceutical |
| Product name: | Herceptin |
| Generic name: | trastuzumab |
| Phase of development: | II |
| Therapeutic area, approved indication: | Breast Cancer |
| Date of report: | 7/3/2006 |
Clinical study summary:
This was a prospective, non comparative, open label study investigating the efficacy and safety of Herceptin (trastuzumab) in combination with cisplatin, epirubicin and paclitaxel, in patients with metastatic breast cancer. The study was prematurely discontinued, due to low recruitment and a poor response rate.
Study center(s) :
1 center in Italy.
Objectives:
Primary: To explore the antitumor activity of Herceptin in combination with cisplatin, epirubicin, and paclitaxel in terms of response rate (RR) in metastatic breast cancer (MBC) patients with HER-2/neu overexpression.
Secondary: To assess duration of response (DR), overall survival (OS), progression-free survival (PFS) and the toxicity of the combination regimen.
Methodology:
Eligible patients were to receive at least 6 cycles of Herceptin in combination with chemotherapy. Patients classified as having a complete response or partial response at the end of cycle 6 were to receive 6 more cycles of Herceptin in combination with chemotherapy. Herceptin alone was to be continued until progressive disease, or unacceptable toxicity, or patient's refusal, or for a maximum of 52 weeks.
Ten patients were included in the study. RR at termination (study endpoint) was limited to 2 of the 10 recruited cases (20%). On this basis, enrollment was stopped and the study was discontinued.
All patients completed Herceptin treatment up to the week 12 assessment, while 5 patients completed treatment up to the week 24 assessment, 4 patients up to the week 36 assessment, 2 patients up to the week 51 assessment and 1 patient completed the study up to the 52-week assessment.
Number of patients (planned/analyzed):
28 planned; 10 enrolled.
Diagnosis and main criteria for inclusion:
MBC patients with HER2/neu overexpression (3+); at least one bidimensionally measurable lesion. No prior chemotherapy for metastatic disease.
Test product, dose and mode of administration or test procedure:
Herceptin (trastuzumab) 4mg/kg loading dose i.v. followed by 2mg/kg i.v., infusions weekly, for a maximum of 52 weeks.
Cisplatin 30mg/m2 i.v. weekly; epirubicin: 50mg/m2 i.v. weekly; paclitaxel: 120mg/m2 i.v. weekly, for a maximum of 12 cycles.
Duration of treatment:
Maximum of 52 weeks
Reference therapy, dose and mode of administration or reference procedure:
N/A
Criteria for evaluation (efficacy, safety):
Efficacy: Complete response (CR) (complete disappearance of all previously detectable disease for a period of at least 28 days, and no new lesions); partial response (PR) (>50% reduction in the sums of the products of the biperpendicular diameters of all measurable disease for a period of at least 28 days, and no new lesions); stable disease (SD) (<50% reduction and <25% increase in the sums of the products of the biperpendicular diameters of all measurable disease and no new lesions); progressive disease (PD) (>25% increase in size of previously documented disease, or the appearance of disease at any site); DR; OS; PFS.
Safety: AEs, laboratory parameters, ECG (if clinically indicated), LVEF.
Statistical methods:
The primary endpoint was the RR (CR plus PR) at the end of the study. Results were calculated and presented with two-sided 95% CI. The primary endpoint efficacy analysis was based on the ITT population (all registered patients who received at least one dose of the study drug). Descriptive safety parameters analysis was carried out in the safety population.
Summary (efficacy, safety, other results):
Efficacy: At study termination 2 patients showed PR, 2 patients SD, while PD was seen in 5 cases, with objective response evaluation not done in 1 patient. Thus a 20.0% RR was seen at termination (95% CI 5.7%-51.0%).
Among the 8 patients with CR or PR at one or more tumor assessment, 6 had data censored at the last progression free observation, including the largest DR value, leading to underestimation of the parameter. In these experimental conditions , DR ranged between 45 and 232 days, with a median value of 217 days.
Five of the 10 patients had data censored at the last progression free observation, including the largest PFS value, leading to underestimation of the parameter. However, the PFS ranged between 98 and 318 days, with a median value of 120 days.
Safety: No deaths occurred during the study, and no patient discontinued the study due to AEs. Six SAEs were reported in 4 patients, two of which (stomatitis and vomiting) were judged to be related to study medications.
The most frequent AEs related to laboratory abnormalities included hemoglobin decrease, LDH increase and neutropenia (10 patients), leukopenia (9 patients), γGT increase (7 patients), SAP increase and SGPT increase (6 patients), SGOT increase and thrombocytopenia (4 patients), lymphocytopenia (3 patients), with all other laboratory AEs reported in single patients. NCI CTC grade 3 or 4 events were limited to 3 cases of grade 3 hemoglobin decrease, 3 cases of grade 3 and 1 grade 4 neutropenia, 3 cases of grade 3 leukopenia and 1 case of grade 3 γGT increase.
Clinical signs and symptoms most frequently reported included alopecia (9 patients), diarrhea and nausea (8 patients), stomatitis (6 patients), asthenia and vomiting (4 patients), with all other signs and symptoms reported in single patients.
ECG and LVEF assessment did not provide evidence of deterioration of cardiac function in any patient. Similarly, laboratory test results did not provide evidence of persisting toxicity when analyzed in terms of shifts of normal/abnormal values at last assessment compared to baseline, except for hemoglobin/hematocrit, frequently shifting from normal baseline to abnormally low values at the last assessment (3 and 4 patients, respectively).
Conclusions:
The study was prematurely discontinued, and the efficacy results (20% RR; 95% CI 5.7% - 51.0%) should be considered inconclusive. The combination of Herceptin with cisplatin, epirubicin, and paclitaxel proved safe and well tolerated when administered with premedication and myelosuppression prophylaxis in this patient population.
Click here for the protocol registry listing of this trial.
