EWOC-1 Trial: Carboplatin +/- Paclitaxel in Vulnerable Elderly Patients With Stage III-IV Advanced Ovarian Cancer
Status:
Completed
Trial end date:
2020-02-01
Target enrollment:
Participant gender:
Summary
The current standard of first-line chemotherapy in advanced ovarian cancer is the combination
of carboplatin AUC 5mg/mL/min and paclitaxel 175 mg.m-². This combination is feasible in
selected elderly patients such as those included in prospective trials. These trials,
however, include a minority of the elderly population. In wider selection of patients >70
years old, the standard carboplatin-paclitaxel regimen has been shown to induce an excess of
toxicity and premature treatment stopping. For elderly patients thought to be vulnerable and
at high risk of toxicity with the standard 3-weekly carboplatin-paclitaxel regimen, other
options are used in routine practice. One option is to delete paclitaxel and treat elderly
patients with carboplatin as a single agent. An alternative is to use the
carboplatin-paclitaxel regimen in a weekly schedule for both drugs such as reported by the
MITO (Multicentre Italian Trial in Ovarian Cancer).
To date, there is no randomized trial which could give us some evidence of how to select
patients who could benefit most of one or the other regimen described above. The 4th Ovarian
Cancer Consensus Conference has indeed recognised the medical unmet need of adapted therapy
for elderly patients with ovarian cancer and the necessity of additional research in this
population.
Recently, GINECO has described a Geriatric Vulnerability Score (GVS) in a population of
elderly patients with advanced ovarian cancer included in a specific multicenter phase II
trial. The best proportional hazard model fitting for overall survival identified the
following geriatric covariates score as being poor survival risk factors: ADL score <6, IADL
score <25, HADS score >14, albuminemia <35g/L and , lymphopenia <1G/L. GVS is the sum of
these risk factors for each patient. Using a cut off of 3, the GVS identified a group of
patients at high risk of severe toxicity, early cessation of treatment, unplanned
hospitalization and adverse outcomes.
This international multicentre randomized phase II trial will compare the success rate of
delivering 6 courses of chemotherapy with evidence of efficacy and without premature
termination for progression, death or unacceptable toxicity of three different chemotherapy
regimens in a selected population of elderly patients with a GVS ≥ 3:
- Arm A: Paclitaxel 175mg/m²/3 hours, I.V. and carboplatin AUC 5, I.V. every 3 weeks
- Arm B: Carboplatin monotherapy AUC 5 or 6 every 3 weeks
- Arm C: Weekly paclitaxel 60 mg/m²/1 hour and weekly carboplatin AUC 2 (d1, d8, d15 every
4 weeks)
The total number of patients to be enrolled is 240, ie 22 in each arm (total = 66) at the
first step, then 58 more by arm (total=174) after interim analysis.