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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10014740 |
E.1.2 | Term | Endometrial cancer stage III |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10014739 |
E.1.2 | Term | Endometrial cancer stage II |
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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10014738 |
E.1.2 | Term | Endometrial cancer stage I |
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 |
Establish overall survival and failure-free survival of patients with high-risk and advanced stage endometrial carcinoma, treated after surgery with concurrent radiotherapy and chemotherapy, followed by adjuvant chemotherapy, in comparison with patients treated with pelvic radiation alone. |
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E.2.2 | Secondary objectives of the trial |
1. Establish and compare rates of treatment-related toxicity
2. Rates of local relapse
3. Rates of distant metastases
4. Quality of Life |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histologically confirmed endometrial carcinoma, grade of differentiation determined according to the
FIGO/AFIP criteria, with one of the following postoperative FIGO 2009 stages45 (Appendix B); confirmed
at pathology review (see section 8.1):
a. Stage IA with myometrial invasion, grade 3 with documented lymph-vascular space invasion (LVSI)
b. Stage IB grade 3
c. Stage II
d. Stage IIIA or IIIC; or IIIB if parametrial invasion
e. Stage IA with myometrial invasion, IB, II or IIIA/C with serous or clear cell histology
During the initial years of the trial, FIGO 1988 staging was used (see Appendix B). Criteria using FIGO
1988 staging:
a. Stage IB grade 3 with documented lymph-vascular space invasion (LVSI)
b. Stage IC or IIA grade 3
c. Stage IIB
d. Stage IIIA* or IIIC *IIIA based on peritoneal cytology alone is only eligible if grade 3
e. Stage IB, IC, II or III with serous or clear cell histology
2. Recommended surgery is TAH-BSO (total abdominal hysterectomy and bilateral salpingooophorectomy).
However, for a patient who has had laparoscopic surgery, and/or lymphadenectomy
and/or full surgical staging, and was found after pathology diagnosis to meet the eligibility criteria,
inclusion in the trial is permitted.
3. WHO-performance status 0-2 (Appendix C)
4. WBC ≥ 3.0 x 109/L.
5. Platelets ≥ 100 x 109/L.
6. Bilirubin ≤ 1.5 x UNL
7. ASAT/ALAT ≤ 2.5 x UNL
8. Written informed consent |
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E.4 | Principal exclusion criteria |
1. Uterine sarcoma
2. Previous malignancy, except for basal cell carcinoma of the skin < 10 years
3. Previous pelvic radiotherapy
4. Hormonal therapy or chemotherapy for this tumor
5. Macroscopic stage IIB for which Wertheim type hysterectomy has been performed
6. Prior diagnosis of Crohn’s disease or ulcerative colitis
7. Residual macroscopic tumor after surgery
8. Impaired renal function: creatinine clearance < 60 ml/min (calculated according to Cockroft) or < 50 ml/min (EDTA clearance, or measured creatinine clearance)
9. Impaired cardiac function, prohibiting the infusion of large amounts of fluid during cisplatin therapy
10. Peripheral Neuropathy > grade 2 |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. 5-year actuarial overall survival
2. 5-year actuarial failure-free survival.
Failure is defined as relapse or death due to endometrial carcinoma or due to treatment complications |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
5 years after randomisation |
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E.5.2 | Secondary end point(s) |
1. Relapse free survival,
2. Overall locoregional failure
3. Overall distant failure |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
5 years after randomisation |
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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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | No |
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 |
Chemotherapy and pelvic radiotherapy versus pelvic radiotherapy alone |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 60 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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The study is based on a recruitment period of 5 years and a follow-up duration of 30 months after inclusion of the last patient before final analysis.
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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 | 10 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 10 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |