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A Phase III Trial of Postoperative Chemotherapy or no Further Treatment for Patients With Node-negative Stage I-II Intermediate or High Risk Endometrial Cancer

Phase 3
18 Years
Open (Enrolling)
Endometrial Cancer

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Trial Information

A Phase III Trial of Postoperative Chemotherapy or no Further Treatment for Patients With Node-negative Stage I-II Intermediate or High Risk Endometrial Cancer

Patients with medium and high risk stage I and II endometrial cancers have, despite radical
surgery, a rather high risk for progression.

Adjuvant radiotherapy was the traditional therapy for many decades. Four randomized phase
III studies and a meta-analysis have revealed that adjuvant radiotherapy improves local
control at the cost of excessive short and long term toxicity, though has absolutely no
impact on survival.

Two phase III studies have randomized between adjuvant radiotherapy versus adjuvant
chemotherapy, both failed to show any difference in survival between radiotherapy and
chemotherapy, though both studies are criticized for inferior chemotherapy regimens or
inclusion of good prognosis patients. The GOG-122 study on more advanced cases (stage 3 & 4)
randomized between combination chemotherapy versus whole abdominal irradiation and found
significant improvement in survival in the chemotherapy arm.

NSGO-EC-9501 and MaNGO studies have indicated that adjuvant chemotherapy added to adjuvant
radiotherapy may improve survival compared to adjuvant radiotherapy alone in early stage
medium and high risk patients. One may conclude that impact on survival comes only from
chemotherapy. Many investigators have therefore adapted adjuvant chemotherapy as standard
treatment in various countries including Denmark. However, such conclusion has low level of
evidence, as there are no randomized phase III studies comparing postoperative observation
alone versus adjuvant chemotherapy.

It is of utmost importance to demonstrate efficacy of adjuvant combination chemotherapy in a
randomized phase III trial comparing to no further treatment in the medium and high risk
node negative stage 1 & 2 patients.

Combination chemotherapy regimen of paclitaxel-carboplatin is proposed in this study, as
this combination is effective and well tolerated.

The eligible patients for such a study are a fraction of patients with endometrial cancer
therefore this study will be performed within the ENGOT collaboration.

Inclusion Criteria:

Target Population

1. Only node-negative patients are eligible: Histological confirmed endometrial
carcinoma with no macroscopic remaining tumour after primary surgery and lymph-node
negative disease, with one of the following postoperative FIGO 2009 stage and grade:

1. Stage I grade 3 endometrioid adenocarcinoma

2. Stage II endometrioid adenocarcinoma

3. Stage I and II type 2 histology (clear cell, serous, squamous cell carcinoma, or
undifferentiated carcinoma) Prior therapy

2. Patients have undergone hysterectomy (total abdominal hysterectomy, radical
hysterectomy, laparoscopic or robotic hysterectomy) and bilateral
salpingo-oophorectomy (BSO) and pelvic lymphadenectomy (LNE).

3. LNE: minimum 12 pelvic nodes (6 from each side) should be removed. Para-aortic LNE is

4. Omentectomy strongly recommended in clear cell, serous or undifferentiated carcinoma.

5. Surgery performed within 10 weeks of randomization. If the dates for hysterectomy and
lymph node dissection are different, 10 weeks are counted from the last surgery, and
in that case the gap between two surgeries should not exceed 8 weeks.

Other inclusion criteria

6. Patients must give informed consent according to the rules and regulations of the
individual participating centres

7. Patients have not received any other anticancer therapy other than surgery.

8. Adjuvant vaginal brachytherapy is permitted in both arms. In chemotherapy arm, timing
of VBT should not cause delay in chemotherapy delivery.

9. Patients must have a WHO performance status of 0-2

10. Patients must have an adequate bone-marrow, renal and hepatic function (WBC
≥3.0x109/L, neutrophils ≥1.5x109/L, platelets ≥100x109/L, total S-bilirubin <2 x
upper normal value, ALAT <2.5 x upper normal value, estimated GFR >50 ml/min
(measured or calculated according to Cockroft-Gault or Jeliffe). Up to 5% deviation
for hematological values and 10% deviation for s-bilirubin and ALAT are tolerated.

11. Life expectancy of at least 12 weeks

12. Patients must be fit to receive combination chemotherapy

13. Patient's age >18 years

Exclusion criteria:

Target Disease Exceptions

1. Carcinosarcoma, Sarcomas or small cell carcinoma with neuroendocrine differentiation.

Prohibited Treatments and/or Therapies

2. External Beam Radiotherapy

3. Concurrent cancer therapy

4. Concurrent treatment with an anticancer investigational agent or participation in
another anticancer clinical trial Other exclusion criteria

5. Previous or concurrent malignant disease except for curatively treated carcinoma in
situ of the cervix or basal cell carcinoma of the skin

6. Active infection or other serious underlying medical condition, which might prevent
the patient from receiving treatment or to be followed

7. Whatever reasons which interferes with an adequate follow-up

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall survival

Outcome Description:

To detect an overall absolute difference in five-year survival of 10%, from 72% to 82%, at the 2.5% level with 80% power, 135 deaths corresponding to 644 patients are needed. Assuming a dropout rate of 5%, 678 patients have to be accrued, leaving 644 patients for the overall analysis.

Outcome Time Frame:

May 2017

Safety Issue:


Principal Investigator

Mansoor R Mirza, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Danish Gynecological Cancer Group


DKMA: The Danish Medicines Agency

Study ID:




Start Date:

December 2011

Completion Date:

January 2018

Related Keywords:

  • Endometrial Cancer
  • endometrial cancer
  • chemotherapy
  • carboplatin
  • paclitaxel
  • Stage 1 & 2
  • node-negative
  • intermediate risk
  • high risk
  • Endometrial Neoplasms
  • Sarcoma, Endometrial Stromal
  • Adenoma