EWOC-1 Trial: Carboplatin +/- Paclitaxel in Vulnerable Elderly Patients With Stage III-IV Advanced Ovarian Cancer

Civil Hospices of Lyon

Status and phase: Completed; Phase 2

Conditions: Ovarian Cancer

Treatments: Drug: Paclitaxel + Carboplatin every 3 weeks; Drug: Carboplatin monotherapy every 3 weeks; Drug: Weekly Paclitaxel and Carboplatin

Study type: Interventional

Funder types: Other

Identifiers

NCT02001272

2012-772

Details and patient eligibility

About

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.

Enrollment: 120 patients

Sex: Female

Ages: 70+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Woman >70 year old
• Histologically or cytologically proven FIGO stage III to IV epithelial ovarian cancer or peritoneal primary or fallopian tube. A cytological proof is accepted if associated with a ratio of CA125/CEA >25 and a radiological pelvic mass.
• GVS (Geriatric Vulnerability Score) >3.
• Adequate bone marrow function including the following: Neutrophils ≥ 1.5 x 109/L , platelets ≥100 x 109/L and hemoglobin ≥9 g/dL.
• Adequate glomerular filtration rate >40 ml/min (estimates based on MDRD or Chatelut formula are sufficient)
• No icterus.
• Life expectancy > 3 months.
• Written informed consent obtained.
• Covered by a Health System where applicable

Exclusion criteria

• Other malignancy within the last 5 years, except for adequately treated carcinoma in situ of the cervix or squamous carcinoma of the skin, or adequately controlled limited basal cell skin cancer.
• Prior history of chemotherapy.
• Prior history of radiotherapy which may affect patient tolerability to chemotherapy.
• Major perturbations of liver biology: Bilirubin > 2 fold the upper normal limit (UNL), SGOT-SGPT > 3 fold UNL.
• Patient unable to be regularly followed for any reason (geographic, familial, social, psychologic).
• Any mental or physical handicap at risk of interfering with the appropriate treatment.
• Known allergy to Cremophor ® EL -containing drugs.
• Any administrative or legal supervision where applicable

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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120 participants in 3 patient groups

A:Paclitaxel + Carboplatin every 3 weeks

Experimental group

Description:

Patients randomized to the arm A receive 6 courses the following regimen: Paclitaxel 175 mg/m²/3 hours, I.V. and carboplatin AUC 5, I.V. every 3 weeks (1 cycle = 21 days).

Treatment:

Drug: Paclitaxel + Carboplatin every 3 weeks

B:Carboplatin monotherapy every 3 weeks

Experimental group

Description:

Patients randomized to the arm B receive 6 courses the following regimen: Carboplatin monotherapy AUC 5 or 6 every 3 weeks (1 cycle = 21 days).

Treatment:

Drug: Carboplatin monotherapy every 3 weeks

C:Weekly Paclitaxel and Carboplatin

Experimental group

Description:

Patients randomized to the arm C receive 6 courses the following regimen: weekly paclitaxel 60 mg/m²/1 hour and weekly carboplatin AUC 2 (d1, d8, d15 ; d1=d29) (1 cycle = 28 days).

Treatment:

Drug: Weekly Paclitaxel and Carboplatin