PETREC: PErsonalized TReatment for Endometrial Carcinoma
Study Details
Study Description
Brief Summary
The goal of this clinical trial is to compare the efficacy of adjuvant therapies in women with stage I-II molecular integrated high-intermediate or high-risk endometrial carcinoma.
Specifically, the invesigators want to compare:
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Chemotherapy vs. chemoradiotherapy in p53 abn subtype and nonendometrioid carcinomas.
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Vaginal brachytherapy vs. whole pelvic radiotherapy in the MMR-D molecular subgroup.
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Vaginal brachytherapy vs. whole pelvic radiotherapy in the NSMP molecular subgroup.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
Endometrial carcinomas can be classified into four molecular subgroups, i.e. mismatch repair deficient (MMR-D), p53 abnormal (p53 abn), polymerase-ϵ (POLE) ultramutated, and "no specific molecular profile" (NSMP). Molecular subgroups can be considered to be distinct diseases as they are associated with different clinicopathologic characteristics, prognoses and, possibly, responses to adjuvant therapy. Molecular classification of endometrial carcinoma is recommended to be implemented in routine clinical practice to improve prognostication and triage to adjuvant therapy. The PErsonalized TReatment for Endometrial Carcinoma (PETREC) trial, led by the Finnish Gynecologic Oncology Group (FINGOG), is a multicenter prospective clinical trial for women with stage I-II molecular integrated high-intermediate or high-risk endometrial carcinoma. The efficacy of chemotherapy vs. chemoradiotherapy is compared in p53 abn subtype and nonendometrioid carcinomas, and vaginal brachytherapy vs. whole pelvic radiotherapy in MMR-D and NSMP molecular subgroups. Patients who consent to follow-up within the trial but not to randomization are treated as recommended in multidisciplinary meetings and enrolled for follow-up only (comprehensive cohort study design). The primary outcome is the 5-year cumulative incidence of disease recurrence. Secondary outcomes are vaginal, pelvic, and distant recurrence rates, 5-year recurrence-free and overall survival, adverse events, and patient-reported symptoms and quality of life. The findings of the trial may eventually help decrease under- and overtreatment and, consequently, improve patient outcome and decrease treatment-associated adverse effects.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: p53 abn subtype and nonendometrioid carcinomas p53 abn stage I-II MI (myometrial invasion) >0%; MMR-D/NSMP nonendometrioid stage I-II MI >0% |
Other: Comparison of adjuvant therapies
Chemotherapy (paclitaxel-carboplatin) vs. chemoradiotherapy (paclitaxel-carboplatin followed by whole pelvic radiotherapy)
Patients assigned to chemotherapy receive paclitaxel (175 mg/m2) and carboplatin (area under curve, 5) every 3 weeks for 6 cycles. The pelvic radiotherapy dose is 45 to 50.4 Gy over 5 to 6 weeks (1.8 Gy per day for 25 to 28 fractions).
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| Experimental: MMR-D molecular subgroup MMR-D stage IA-B grade 1-2, substantial LVSI; MMR-D stage IA grade 3, substantial LVSI; MMR-D stage IB grade 3; MMR-D stage II grade 1-3; |
Other: Comparison of adjuvant therapies
Vaginal brachytherapy vs. whole pelvic radiotherapy
Patients randomized to vaginal brachytherapy receive cuff brachytherapy at 21 Gy in 3 fractions of 7 Gy at 0.5 cm depth. The pelvic radiotherapy dose is 45 to 50.4 Gy over 5 to 6 weeks (1.8 Gy per day for 25 to 28 fractions).
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| Experimental: NSMP molecular subgroup NSMP stage IA-B grade 1-2, substantial LVSI; NSMP stage IA grade 3, substantial LVSI; NSMP stage IB grade 3; NSMP stage II grade 1-3; |
Other: Comparison of adjuvant therapies
Vaginal brachytherapy vs. whole pelvic radiotherapy
Patients randomized to vaginal brachytherapy receive cuff brachytherapy at 21 Gy in 3 fractions of 7 Gy at 0.5 cm depth. The pelvic radiotherapy dose is 45 to 50.4 Gy over 5 to 6 weeks (1.8 Gy per day for 25 to 28 fractions).
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Outcome Measures
Primary Outcome Measures
- Cancer reappearance [5 years]
Cumulative incidence of disease recurrence
Secondary Outcome Measures
- Location of cancer reappearance [5 years]
Vaginal, pelvic, and distant recurrence rates
- Overall survival [5 years]
The time from surgery to death
- Recurrence-free survival [5 years]
The time from surgery to cancer recurrence
- Adverse events [5 years]
Adjuvant therapy-related adverse events
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age 18 to 100 years
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WHO performance status 0 to 2
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Stage I-II molecular integrated high-intermediate or high-risk endometrial carcinoma
Exclusion Criteria:
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Age <18 years or >100 years
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WHO performance status >2
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Uterine sarcoma
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A history of malignancy within 5 years
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Previous pelvic radiotherapy
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An interval of >30 days between surgery and start of chemotherapy or >8 weeks between surgery and start of radiotherapy (longer intervals may be permitted with investigator´s approval)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Helsinki University Hospital | Helsinki | Finland | 00290 |
Sponsors and Collaborators
- University of Helsinki
- Päijät-Häme Central Hospital
- South Carelia Central Hospital
- Kymenlaakso Central Hospital Kotka Finland
- Turku University Hospital
- Tampere University Hospital
- Kuopio University Hospital
- Oulu University Hospital
Investigators
- Principal Investigator: Mikko Loukovaara, Helsinki University Central Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- HUS/2360/2021