PErsonalized TReatment for Endometrial Carcinoma

NCT ID: NCT05655260

Last Updated: 2024-12-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-08
• Study Completion Date: 2028-12-31

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:

• 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.

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.

Conditions

Endometrial Adenocarcinoma

Keywords

Endometrial carcinoma; Molecular classification; Adjuvant therapy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

p53 abn subtype and nonendometrioid carcinomas

p53 abn stage I-II MI (myometrial invasion) \>0%; MMR-D/NSMP nonendometrioid stage I-II MI \>0%

Group Type: EXPERIMENTAL

Comparison of chemotherapy vs. chemoradiotherapy

Intervention Type: OTHER

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).

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;

Group Type: EXPERIMENTAL

Comparison of VBT vs. WPRT

Intervention Type: OTHER

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).

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;

Group Type: EXPERIMENTAL

Comparison of VBT vs. WPRT

Intervention Type: OTHER

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).

Interventions

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).

Intervention Type: 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).

Intervention Type: OTHER

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Turku University Hospital

OTHER_GOV

Sponsor Role: collaborator

Tampere University Hospital

OTHER

Sponsor Role: collaborator

Kuopio University Hospital

OTHER

Sponsor Role: collaborator

Oulu University Hospital

OTHER

Sponsor Role: collaborator

Kymenlaakso Central Hospital Kotka Finland

OTHER

Sponsor Role: collaborator

Päijänne Tavastia Central Hospital

OTHER

Sponsor Role: collaborator

South Carelia Central Hospital

OTHER

Sponsor Role: collaborator

University of Helsinki

OTHER

Sponsor Role: lead

Responsible Party

Mikko Loukovaara

Chief of Specialists, MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mikko Loukovaara

Role: PRINCIPAL_INVESTIGATOR

Helsinki University Central Hospital

Locations

Helsinki University Hospital

Helsinki, , Finland

Site Status: RECRUITING

Countries

Finland

Central Contacts

Mikko Loukovaara

Role: CONTACT

Phone: +358504272526

Email: mikko.loukovaara@hus.fi

Ralf Bützow

Role: CONTACT

Phone: +358504271899

Email: ralf.butzow@hus.fi

Facility Contacts

Mikko Loukovaara, MD

Role: primary

Ralf Bützow, MD

Role: backup

References

Loukovaara M, Butzow R, Staff S, Maenpaa M, Faltinova M, Lassus H, Veijalainen O, Gronvall M, Vaalavirta L, Kuikka E, Haataja M, Urpilainen E, Simojoki M, Anttila M, Auranen A. PErsonalized TReatment for Endometrial Carcinoma (PETREC): study design and methods of a prospective Finnish multicenter trial. Int J Gynecol Cancer. 2023 Nov 6;33(11):1807-1811. doi: 10.1136/ijgc-2023-004939.

Reference Type: DERIVED

PMID: 37813479 (View on PubMed)

Other Identifiers

HUS/2360/2021

Identifier Type: -

Identifier Source: org_study_id