PErsonalized TReatment for Endometrial Carcinoma (PETREC)

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:

• Chemotherapy vs. chemoradiotherapy in p53 abn subtype and nonendometrioid carcinomas.
• Vaginal brachytherapy vs. whole pelvic radiotherapy in the MMR-D molecular subgroup.
• Vaginal brachytherapy vs. whole pelvic radiotherapy in the NSMP molecular subgroup.

Study Overview

• Status: Recruiting
• Conditions: Endometrial Adenocarcinoma
• Intervention / Treatment: Other: Comparison of chemotherapy vs. chemoradiotherapy; Other: Comparison of VBT vs. WPRT

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 Type: Interventional
• Enrollment (Estimated): 300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mikko Loukovaara; Phone Number: +358504272526; Email: mikko.loukovaara@hus.fi
• Study Contact Backup: Name: Ralf Bützow; Phone Number: +358504271899; Email: ralf.butzow@hus.fi

Study Locations

• Finland
  • Helsinki, Finland, 00290
    • Recruiting
    • Helsinki University Hospital
    • Contact: Mikko Loukovaara, MD; Phone Number: +358504272526; Email: mikko.loukovaara@hus.fi
    • Contact: Ralf Bützow, MD; Phone Number: +358504271899; Email: ralf.butzow@hus.fi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 96 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18 to 100 years
• WHO performance status 0 to 2
• Stage I-II molecular integrated high-intermediate or high-risk endometrial carcinoma

Exclusion Criteria:

• Age <18 years or >100 years
• WHO performance status >2
• Uterine sarcoma
• A history of malignancy within 5 years
• Previous pelvic radiotherapy
• 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / 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 chemotherapy vs. chemoradiotherapy; 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).
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 VBT vs. WPRT; 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).
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 VBT vs. WPRT; 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cancer reappearance	Cumulative incidence of disease recurrence	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Location of cancer reappearance	Vaginal, pelvic, and distant recurrence rates	5 years
Overall survival	The time from surgery to death	5 years
Recurrence-free survival	The time from surgery to cancer recurrence	5 years
Adverse events	Adjuvant therapy-related adverse events	5 years

Collaborators and Investigators

• Sponsor: University of Helsinki
• Collaborators: Turku University Hospital; Oulu University Hospital; Kuopio University Hospital; Tampere University Hospital; Päijänne Tavastia Central Hospital; Kymenlaakso Central Hospital Kotka Finland; South Carelia Central Hospital
• Investigators: Principal Investigator: Mikko Loukovaara, Helsinki University Central Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2022
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: November 30, 2022
• First Submitted That Met QC Criteria: December 8, 2022
• First Posted (Actual): December 19, 2022

Study Record Updates

• Last Update Posted (Estimated): December 6, 2024
• Last Update Submitted That Met QC Criteria: December 3, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Adjuvant therapy; Endometrial carcinoma; Molecular classification
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Uterine Diseases; Genital Diseases, Female; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Uterine Neoplasms; Carcinoma; Endometrial Neoplasms
• Other Study ID Numbers: HUS/2360/2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No