E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10070908 |
E.1.2 | Term | Ovarian cancer stage IV |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10070907 |
E.1.2 | Term | Ovarian cancer stage III |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the success rate of 3 different chemotherapy regimens in women > 70 with ovarian cancer stage III-IV, considered as vulnerable upon defined Geriatric Vulnerability Score (GVS). Success is defined as the ability to deliver to patients 6 courses of chemotherapy without premature termination for progression, death or unacceptable toxicity. |
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E.2.2 | Secondary objectives of the trial |
- Therapeutical strategy (feasibility of performing an optimal surgery and feasibility of performing neoadjuvant chemotherapy and surgery and post operative chemotherapy until 6 courses)
- Interval debulking feasibility
- Post-operative chemotherapy feasibility
- Progression-free Survival (PFS)
- Overall Survival (OS)
- Quality of life (QOL)
- Safety and tolerability
- Geriatric covariates and patient outcome
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Title : Impact of aging biomarkers on overall survival
Version : 1.0
Date : 2013-03-08
Objective : The expression level of aging biomarkers (cathelin-related antimicrobial peptide or CRAMP, stathmin, EF-1α, and chitinase) will be measured in order to test a possible correlation between high biomarker rates and either a decreased treatment completion rate, an increased risk of chemo-induced toxicities or a decreased overall survival. |
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E.3 | Principal inclusion criteria |
- Woman >70 year old: a patient can be included the day after her 70th birthday.
- 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. GVS is the sum of geriatric covariates scores found to predict poor survival: ADL score <6; IADL score <25, HADS score >14, albuminemia <35g/L and lymphopenia <1G/L.
- 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 CKD-EPI formula are sufficient)
- No icterus.
- Life expectancy > 3 months.
- Written informed consent obtained
- Covered by a Health System where applicable |
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E.4 | Principal 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 for the present malignancy
- 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Success rate of delivering one of the 3 different chemotherapy regimens Treatment success is defined as the ability to deliver 6 courses of chemotherapy without premature termination for progression, death or unacceptable toxicity.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After 6 courses of chemotherapy |
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E.5.2 | Secondary end point(s) |
1) Therapeutical strategy
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. Interval debulking surgery feasibility and post-operative chemotherapy will also be assessed.
2) Overall Survival
Overall survival will be analyzed on going by Kaplan-Meier method and will be estimated at 1 and 2 years (data points) for each treatment arm. Overall survival will be measured from date of randomization to death from any cause or the date of last contact (censored data). An univariate analysis will be performed using the log-rank technique to determine the prognostic role geriatric covariates and aging biomarkers. The adjusted prognostic value will be estimated in a multivariate analysis using a cox proportional hazards model.
3) Geriatric assessment and biological covariates
For the study of geriatric covariates
- Analysis of covariates of the geriatric assessment (percentages).
- Estimation of the correlation between the parameters of the geriatric assessment and treatment toxicity, tumor response, overall survival and progression-free survival (correlation tests).
Geriatric covariates distribution, by type and by patient as well as baseline biological values will be described and presented for each treatment arm in tables.
4) Safety, feasibility and efficacy of chemotherapy related covariates
- Feasibility of six courses of chemotherapy
The proportion of patients who completed 6 courses will be presented for each treatment arm with its confidence interval. The possible impact of geriatric prognostic factors will be estimated using a logistic regression (multivariate analysis).
- Chemotherapy related toxicity
Analysis of toxicities related to chemotherapy, which will be collected for each treatment and scored according to NCI-CTC V4.03 grade. Distributions of toxic events, by type of toxicity, by grade, by course and by patient, and for all courses (evaluated at the 30th week) will be described and presented for each treatment arm in tables.
- Analysis of specific survival and progression-free survival
Specific survival will be calculated for each treatment arm from date of randomization to deaths unrelated to cancer as censorship or date of last contact (censored data). It will be analyzed using Kaplan-Meier method and will be estimated at 1 and 2 years. A multivariate analysis will be performed using a proportional hazards model.
Progression-free survival will consider the disease progression defined by clinical examination, ultrasound or CT-scan, increased CA-125.
- Analysis of tumor response rate
Evaluated for each treatment arm at the 30th week, it will consider the following criteria:
* CT scan 2 dimensions measurable mass, RECIST criteria
* CA-125 rates evolution
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After 6 courses of chemotherapy , 1 year, 2 years |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Comparaison between 3 different chemotherapy regimens |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 80 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Denmark |
Finland |
France |
Germany |
Italy |
Japan |
Norway |
Sweden |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 6 |