Chemotherapy or Observation in Stage I-II Intermediate or High Risk Endometrial Cancer
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01244789|
Recruitment Status : Recruiting
First Posted : November 19, 2010
Last Update Posted : February 2, 2018
Patients with stage 1 & 2 endometrial cancer are treated with surgery. Despite the fact that disease is confound to uterus, unfortunately some of these patients may relapse and die of their disease. Postoperative radiotherapy cannot improve survival. Chemotherapy has shown survival benefit in more advanced stage disease (stage 3 & 4).
This study evaluates if one can improve survival in intermediate and high risk early-stage patients by offering them postoperative chemotherapy. This is a randomized phase 3 trial where effect of postoperative chemotherapy is compared with postoperative observation alone (standard strategy).
Substudy: Translational research
|Condition or disease||Intervention/treatment||Phase|
|Endometrial Cancer||Drug: carboplatin and paclitaxel Other: observation||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||240 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Randomized Trial of Postoperative Chemotherapy or no Further Treatment for Patients With Node-negative Stage I-II Intermediate or High Risk Endometrial Cancer|
|Actual Study Start Date :||December 2011|
|Estimated Primary Completion Date :||January 2020|
|Estimated Study Completion Date :||January 2023|
Active Comparator: Observation
postoperative observation only
Experimental: Combination chemotherapy
postoperative 6 courses of 3 weekly iv carboplatin-paclitaxel combination chemotherapy
Drug: carboplatin and paclitaxel
6 courses of iv 3-weekly chemotherapy Carboplatin AUC5 Paclitaxel 175mg/m2
- Overall survival [ Time Frame: May 2017 ]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.
- Overall Survival in endometrioid subgroup [ Time Frame: May 2017 ]In the endometrioid subgroup an absolute difference in five-year survival of 12%, from 74% to 86% is expected. Assuming this, 79 deaths corresponding to 438 patients are needed to yield 80% power at the 2.5% level. Assuming a dropout rate of 5%, 678 patients have to be accrued, leaving 644 patients for the overall analysis and 75% of these, or 483 patients, for the analysis in the endometrioid subgroup.
- Disease Specific Survival [ Time Frame: May 2017 ]Exploratory endpoint
- Progression-Free Survival [ Time Frame: May 2017 ]Exploratory endpoint
- Toxicity [ Time Frame: May 2017 ]Acute toxicity (0-6 months from randomization). Late toxicity is registered during whole study period. Exploratory endpoint
- Quality of Life [ Time Frame: May 2017 ]EORTC QLQ-30 EORTC QLQ-EN-34
- Rate of isolated pelvic relapse [ Time Frame: May 2017 ]Exploratory endpoint
- Rate of isolated distant relapse [ Time Frame: May 2017 ]Exploratory endpoint
- Rate of mixed (local & distant) relapses [ Time Frame: May 2017 ]Exploratory endpoint
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01244789
|Contact: Mansoor R Mirza, MDfirstname.lastname@example.org|
|Contact: Dorte Nørvang, CRNemail@example.com|
|Danish Gynecological Cancer Group (DGCG)||Recruiting|
|Copenhagen, Denmark, 2100|
|Contact: Dorte Nørvang, CRN +4535453311 firstname.lastname@example.org|
|Principal Investigator: Mansoor R Mirza, MD|
|Study Chair:||Mansoor R Mirza, MD||Danish Gynecological Cancer Group|