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 I and stage II patients.
Source
Brief title
Condition
- Reproductive neoplasms female malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
No registrations found.
Outcome measures
Primary outcome
The primary endpoint is to evaluate the overall survival.
Secondary outcome
Secondary objectives are disease specific survival, progression-free survival,
rates of isolated pelvic (central or pelvic wall), distant and mix relapses,
quality of life, compliance and toxicity.
Background summary
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 III
and IV) 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 I and stage II 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 and with centres
outside ENGOT.
Study objective
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 I and stage II patients.
Study design
This multicenter, prospective, open-label, randomized, controlled study is
evaluating postoperative chemotherapy compared with no further treatment in
treating patients with medium- or high-risk, node negative stage I, or stage II
endometrial cancer.
Intervention
Patients are randomized to one of the two treatment arms
1:1 randomization (chemotherapy vs. observation):
• Arm I: Patients receive postoperative adjuvant intravenous paclitaxel and
intravenous carboplatin. Adjuvant chemotherapy repeats every three
weeks, six courses
• Arm II: Patients postoperatively are followed-up without any further
treatment
Study burden and risks
Chemotherapy can cause side effects. Carboplatin and paclitaxel have been used
for 15 years for patients with metastatic uterine cancer and ovarian cancer
patients. The patients usually tolerate the treatment well. The estimated risk
is low.
Blegdamsvej 9
Kopenhagen 2100
DK
Blegdamsvej 9
Kopenhagen 2100
DK
Listed location countries
Age
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:;a.Stage I grade 3 endometrioid adenocarcinoma;b.Stage II endometrioid adenocarcinoma;c.Stage I and II type 2 histology (clear cell, serous, or squamous cell carci-noma, or undifferentiated carcinoma);2. Patients with prior therapy: ;a. Patients have undergone hysterectomy (total abdominal hysterectomy (TAH), radical hysterectomy, laparoscopic or robotic hysterectomy) and bilateral salpingo-oopherectomy (BSO) (or RH) and+ pelvic lymphadenectomy (LNE).;b. LNE: minimum 12 pelvic nodes (6 from each side) should be removed. Para-aortic LNE is optional;c. Omentectomy strongly recommended in clear cell, serous, squamous cell carcinoma or undifferentiated carcinoma;d. Surgery performed within 10 weeks of randomization. If the dates for hys-terectomy 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. ;3. Other inclusion criteria;a. Patients must give informed consent according to the rules and regulations of the individual participating centres;b. Patients have not received any other anticancer therapy other than surgery.;c. Adjuvant vaginal brachytherapy permitted in both arms. In chemotherapy arm, timing of VBT should not cause delay in chemotherapy delivery. ;d. Patients must have WHO performance status of 0-2 ;e. 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.;f. Life expectancy of at least 12 weeks;g. Patients must be fit to receive combination chemotherapy;h. Patient*s age > 18 years
Exclusion criteria
1. Target disease exclusions:;•Carcinosarcoma, Sarcomas or small cell carcinoma with neuroendocrine differen-tiation. ;2. Prohibited Treatments and/or Therapies;•External Beam Radiotherapy;•Concurrent cancer therapy;•Concurrent treatment with an anticancer investigational agent or participation in another anticancer clinical trial;3. Other exclusion criteria;•Previous or concurrent malignant disease except for curatively treated carcinoma in situ of the cervix or basal cell carcinoma of the skin;•Active infection or other serious underlying medical condition, which might prevent the patient from receiving treatment or to be followed;•Whatever reasons which interferes with an adequate follow-up
Patients who are breast feeding must stop breast feeding
before enrolment in the trial and must not do so during the whole trial period, otherwise these patients are non-eligible
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
Register | ID |
---|---|
EudraCT | EUCTR2010-023081-52-NL |
ClinicalTrials.gov | NCT01244789 |
CCMO | NL43277.018.15 |