Clinical trial NCT05640999: Adjuvant Therapy in POLE-Mutated and p53-Wildtype/NSMP Early Stage Endometrial Cancer RAINBO BLUE & TAPER
Official title: A Phase II Study of Tailored Adjuvant Therapy in POLE-Mutated and p53-Wildtype/NSMP Early Stage Endormetrial Cancer (RAINBO BLUE & TAPER)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Endometrial Cancer
Lead sponsor: Canadian Cancer Trials Group
Sponsor class: NETWORK
Collaborators: name: Canadian Cancer Clinical Trials Network
First posted: 2022-12-07
Enrollment: 393
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This protocol tests de-escalated adjuvant treatment in patients with POLE-mutated or p53wt/NSMP (p53 wildtype/no specific molecular profile) early-stage endometrial cancer (EC). Patients may be enrolled in one of two sub-studies

* EN10.A/RAINBO BLUE: POLE-mutated EC
* EN10.B/TAPER: p53 wildtype / NSMP EC

Detailed description: This study is being done in order to find out if this new approach is better or worse than the usual approach for early-stage endometrial cancer. The usual approach is defined as the care most people get for early-stage endometrial cancer.

The usual approach for patients who are not in a study is treatment with surgery. Tissue that is removed as part of this procedure is analyzed in the pathology laboratory to guide the doctor to decide whether or not additional treatment such as radiation and or chemotherapy should be recommended.

Eligibility criteria: Inclusion Criteria:

* Patients must have had surgery consisting of hysterectomy and bilateral salpingo-oophorectomy. Lymph node dissection can be performed as per institutional standards. There must be no macroscopic residual disease after surgery.
* Patients must have histologically confirmed Stage I to III endometrial carcinoma which can be endometrioid, serous, clear cell, un/dedifferentiated, carcinosarcoma or mixed.
* Patients' Eastern Cooperative Group (ECOG) performance status must be 0, 1, or 2.
* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
* Patients' age must be ≥ 18 years.
* Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements.
* Patient is able (i.e. sufficiently fluent) and willing to complete the patient-reported outcomes (PRO) questionnaires in either English, French or a validated language
* Patients must be accessible for treatment and follow-up. Patients enrolled on this trial must be treated and followed at the participating centre
* Protocol treatment is to begin within 10 weeks of hysterectomy/bilateral salpingo-oophorectomy

Exclusion Criteria:

* Prior Neoadjuvant chemotherapy for current endometrial cancer diagnosis.
* Prior pelvic radiation.
* Patients with a history of other malignancies, except: carcinoma in-situ without evidence of invasive disease when resected, adequately treated non-melanoma skin cancer, or other tumours curatively treated with no evidence of disease for ≥ 5 years.
* Clinical evidence of distant metastasis as determined by pre-surgical or post-surgical imaging (CT scan of chest, abdomen and pelvis or whole-body PET-CT scan)
* Patients with a documented positive surgical margin.
* Patients with a documented positive peritoneal washings, if performed.

Primary outcomes:
measure: Estimate the rate of pelvic recurrence at 3 years in patients who are treated with de-escalated adjuvant treatment directed by tumour molecular status
timeFrame: 3 years
Secondary outcomes:
measure: Estimate the rate of isolated vaginal recurrence at 3 years
timeFrame: 3 years
measure: Estimate the rate of para-aortic recurrence at 3 years
timeFrame: 3 years
measure: Estimate the rate of distant metastasis at 3 years
timeFrame: 3 years
measure: Estimate recurrence-free survival
timeFrame: 9 years
measure: Estimate endometrial cancer-specific survival
timeFrame: 9 years
measure: Estimate overall survival
timeFrame: 9 years
measure: Describe the impact of molecular classification on fear of recurrence by Fear of Recurrence Inventory
timeFrame: 9 years
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Alaska Womens Cancer Care
state: Alaska
city: Tucson
country: United States
facility: University of Arizona Cancer Center
state: Arizona
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Pasadena
country: United States
facility: Huntington Memorial Hospital
state: California
city: Sacramento
country: United States
facility: Sutter Medical Center Sacramento
state: California
city: Aurora
country: United States
facility: UCHealth University of Colorado Hospital
state: Colorado
city: Atlanta
country: United States
facility: Piedmont Hospital
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Warrenville
country: United States
facility: Northwestern Medicine Cancer Center Warrenville
state: Illinois
city: Indianapolis
country: United States
facility: Ascension Saint Vincent Indianapolis Hospital
state: Indiana
city: New Orleans
country: United States
facility: University Medical Center New Orleans
state: Louisiana
city: Worcester
country: United States
facility: UMass Memorial Medical Centre
state: Massachusetts
city: Sewell
country: United States
facility: Sidney Kimmel Cancer Center Washington Township
state: New Jersey
city: New York
country: United States
facility: Mount Sinai Chelsea
state: New York
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: Oswego
country: United States
facility: Upstate Cancer Center Radiation Oncology at Oswego
state: New York
city: Syracuse
country: United States
facility: State University of New York
state: New York
city: Syracuse
country: United States
facility: Upstate Cancer Center at Hill Radiation Oncology
state: New York
city: Verona
country: United States
facility: Upstate Cancer Center at Verona
state: New York
city: Chapel Hill
country: United States
facility: UNC Lineberger Comprehensive Cancer Center
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Raleigh
country: United States
facility: Duke Womens Cancer Care Raleigh
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Comprehensive
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Hershey
country: United States
facility: Penn State Milton S Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Willow Grove
country: United States
facility: Asplundh Cancer Pavilion
state: Pennsylvania
city: Providence
country: United States
facility: Women and Infants Hospital
state: Rhode Island
city: Farmington
country: United States
facility: Farmington Health Centre
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah Sugarhouse Health Centre
state: Utah
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute University of Utah
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Cancer Center
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Liverpool
country: Australia
facility: South Western Sydney Local Health District
state: New South Wales
city: Waratah
country: Australia
facility: Calvary Mater Newcastle Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: South Brisbane
country: Australia
facility: Mater Research Institute South Brisbane
state: Queensland
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Frankston
country: Australia
facility: Frankston Hospital
state: Victoria
city: Parkville
country: Australia
facility: The Royal Women's Hospital
state: Victoria
city: Garran
country: Australia
facility: Canberra Hospital
city: Herston
country: Australia
facility: Royal Brisbane and Womens Hospital
city: Calgary
country: Canada
facility: Arthur J.E. Child Comprehensive Cancer Centre
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Kelowna
country: Canada
facility: BCCA - Kelowna
state: British Columbia
city: Prince George
country: Canada
facility: BCCA - Prince George
state: British Columbia
city: Vancouver
country: Canada
facility: BCCA - Vancouver
state: British Columbia
city: Victoria
country: Canada
facility: BCCA - Victoria
state: British Columbia
city: London
country: Canada
facility: London Health Sciences Centre Research Inc.
state: Ontario
city: Mississauga
country: Canada
facility: Trillium Health Partners - Credit Valley Hospital
state: Ontario
city: Toronto
country: Canada
facility: Odette Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Montreal
country: Canada
facility: CHUM-Centre Hospitalier de l'Universite de Montreal
state: Quebec
city: Montreal
country: Canada
facility: The Jewish General Hospital
state: Quebec
city: Sherbrooke
country: Canada
facility: CIUSSS de l'Estrie - Centre hospitalier
state: Quebec
city: Villejuif
country: France
facility: Institut Gustave-Roussy
state: FR
city: Toulouse
country: France
facility: Institut Universitaire du Cancer de Toulouse - IUCT
state: Occitanie
city: Milan
country: Italy
facility: European Institute of Oncology
city: Arnhem
country: Netherlands
facility: Radiotherapiegroep
state: Gelderland
city: Maastricht
country: Netherlands
facility: Maastro clinic (Maastricht UMC)
state: Limburg
city: Eindhoven
country: Netherlands
facility: Catharina ziekenhuis
state: Noord Brabant
city: Den Haag
country: Netherlands
facility: MC Haaglanden
state: South Holland
city: Leiden
country: Netherlands
facility: Leiden University Medical Center (LUMC)
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center (EMC)
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
Study officials:
affiliation: University Health Network, Princess Margaret Hospital, Toronto ON Canada
name: Kathy Han
role: STUDY_CHAIR
affiliation: BCCA-Vancouver Cancer Centre, Vancouver BC Canada
name: Jessica McAlpine
role: STUDY_CHAIR
References: