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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Hospices Civils de Lyon
Sponsor:
Information provided by (Responsible Party):
Hospices Civils de Lyon
ClinicalTrials.gov Identifier:
NCT02001272
First received: November 22, 2013
Last updated: January 14, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Ovarian Cancer
Drug: Paclitaxel + Carboplatin every 3 weeks
Drug: Carboplatin monotherapy every 3 weeks
Drug: Weekly Paclitaxel and Carboplatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: EWOC-1 Trial: Multicenter, Randomized Trial of Carboplatin +/- Paclitaxel in Vulnerable Elderly Patients With Stage III-IV Advanced Ovarian Cancer

Resource links provided by NLM:


Further study details as provided by Hospices Civils de Lyon:

Primary Outcome Measures:
  • Treatment success.Treatment success is defined as the ability to deliver 6 courses of chemotherapy without premature termination for progression, death or unacceptable toxicity [ Time Frame: After 6 courses of chemotherapy i.e 4.5 to 6 months (depending on the arm) ] [ Designated as safety issue: Yes ]
    Treatment success is defined as the ability to deliver 6 courses of chemotherapy without premature termination for progression, death or unacceptable toxicity. Unacceptable toxicity is defined as a major adverse event related to chemotherapy or treatment procedure leading either to early treatment stopping, to an unplanned hospital admission or to death or to a dose delay lasting more than 14 days or more than 2 dose reductions.


Secondary Outcome Measures:
  • Therapeutical strategy [ Time Frame: At the end of treatment (6 courses ), i.e 4.5 to 6 months (depending on the arm) ] [ Designated as safety issue: Yes ]
    Therapeutical strategy will be assessed by measuring the feasibility of performing an optimal surgery and feasibility of performing neoadjuvant chemotherapy and surgery and post operative chemotherapy until 6 courses in case of planned interval debulking surgery.

  • Overall Survival [ Time Frame: 2.5 years ] [ Designated as safety issue: Yes ]
    Overall survival is defined as the time period from the date of randomization to the date of death.

  • Progression-free survival [ Time Frame: 2.5 years ] [ Designated as safety issue: Yes ]
    Progression-free survival is defined as the time period from the date of randomization to the date of disease progression or death whichever occurs first.

  • Quality of Life [ Time Frame: At the end of treatment (6 courses ), i.e 4.5 to 6 months (depending on the arm) ] [ Designated as safety issue: No ]
    Quality of life is evaluated using the FACT-O questionnaire

  • Safety and tolerability [ Time Frame: At the end of treatment (6 courses ), i.e 4.5 to 6 months (depending on the arm) ] [ Designated as safety issue: Yes ]
    Adverse events are defined using the NCI-CTC AE scale version 4.3

  • Aging biomarkers [ Time Frame: At the end of treatment (6 courses ), i.e 4.5 to 6 months (depending on the arm) ] [ Designated as safety issue: No ]
    Aging biomarkers are represented by the expression level of cathelin-related antimicrobial peptide or CRAMP, stathmin, EF-1α, and chitinase


Estimated Enrollment: 240
Study Start Date: November 2013
Estimated Study Completion Date: July 2018
Estimated Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A:Paclitaxel + Carboplatin every 3 weeks
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).
Drug: Paclitaxel + Carboplatin every 3 weeks
Patients will receive a premedication of 130mg prednisolone the day before (22 pm) and the morning (7 am). A pretreatment using corticosteroids, antihistamines and H2 antagonists and setrons in accordance with local standards of care will be administered 30 minutes before Paclitaxel administration. At H0, Paclitaxel is administered at 175mg/m² in 3 hours then Carboplatin is administered at AUC 5mg/mL/min.
Experimental: B:Carboplatin monotherapy every 3 weeks
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).
Drug: Carboplatin monotherapy every 3 weeks
A pretreatment using setrons in accordance with local standards of care will be administered 30 minutes before Carboplatin at AUC 5 to 6mg/mL/min in 1 hour.
Experimental: C:Weekly Paclitaxel and Carboplatin
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).
Drug: Weekly Paclitaxel and Carboplatin
A pretreatment using corticosteroids, antihistamines and H2 antagonists and setrons in accordance with local standards of care will be administered 30 minutes before Paclitaxel 60mg/m² in 1 hour followed by Carboplatin at AUC 2mg/mL/min in 1 hour.

  Eligibility

Ages Eligible for Study:   70 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02001272

Contacts
Contact: Claire FALANDRY, MD 4 78 86 15 80 ext +33 claire.falandry@chu-lyon.fr
Contact: Nathalie LE FUR 1 42 34 83 23 ext +33 nlefur@arcagy.org

Locations
France
Service oncogériatrie, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon Recruiting
Pierre-Bénite, France, 69495
Contact: Claire FALANDRY, MD    4 78 86 15 80 ext +33    claire.falandry@chu-lyon.fr   
Principal Investigator: Claire FALANDRY, MD         
Sponsors and Collaborators
Hospices Civils de Lyon
Investigators
Principal Investigator: Claire FALANDRY, MD Service d'oncogériatrie, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon
  More Information

Additional Information:
No publications provided

Responsible Party: Hospices Civils de Lyon
ClinicalTrials.gov Identifier: NCT02001272     History of Changes
Other Study ID Numbers: 2012-772
Study First Received: November 22, 2013
Last Updated: January 14, 2014
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by Hospices Civils de Lyon:
Elderly
Vulnerable
Ovarian cancer
Chemotherapy

Additional relevant MeSH terms:
Ovarian Neoplasms
Endocrine Gland Neoplasms
Genital Neoplasms, Female
Neoplasms
Neoplasms by Site
Ovarian Diseases
Urogenital Neoplasms
Adnexal Diseases
Endocrine System Diseases
Genital Diseases, Female
Gonadal Disorders
Carboplatin
Paclitaxel
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on November 20, 2014