Clinical trial NCT06388018: Tailoring Therapy in Post-surgical Patients With Low-risk Endometrial Cancer
Official title: A Phase II Study of Tailored Adjuvant Therapy in Pole-Mutated and p53-Wildtype/NSMP Early-Stage Endometrial Cancer (RAINBO BLUE &Amp; TAPER)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Stage I Uterine Corpus Endometrial Stromal Sarcoma AJCC v8
Stage II Uterine Corpus Endometrial Stromal Sarcoma AJCC v8
Stage III Uterine Corpus Endometrial Stromal Sarcoma AJCC v8
Lead sponsor: NRG Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2024-04-29
Enrollment: 325
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 phase II trial tests how well tailoring therapy in post-surgery works in patients with low-risk endometrial cancer. The usual approach for patients with low-risk endometrial cancer is treatment with surgery. In this study, tissue that is removed as part of the surgical procedure is analyzed in the pathology laboratory to help guide the doctor to decide whether or not additional treatment such as radiation and or chemotherapy should be recommended.

Detailed description: PRIMARY OBJECTIVE:

I. Estimate the rate of pelvic recurrence at 3 years in patients who are treated with a de-escalated adjuvant treatment directed by tumour molecular status.

SECONDARY OBJECTIVES:

I. Estimate the rate of isolated vaginal recurrence, para-aortic recurrence and distant metastasis at 3 years.

II. Estimate the recurrence-free, endometrial cancer-specific and overall survival.

III. Describe the impact of molecular classification on patient decisional conflict and fear of recurrence.

TERTIARY OBJECTIVES:

I. Evaluate health economic impact of molecular classification-tailored adjuvant therapy on the cost of treating endometrial cancer.

II. Evaluate quality of life. III. Determine if variability in adjuvant treatment given to patients with endometrial cancer is decreased by molecular classification-tailored adjuvant therapy as compared to recent clinical practice data.

IV. To assess if additional molecular parameters can further refine prognosis within POLE-mutated and p53wt/no specific molecular profile (NSMP) endometrial cancer (EC).

OUTLINE: Patients are assigned to 1 of 2 sub-studies.

SUB-STUDY A: Patients are assigned to 1 of 2 cohorts.

COHORT A1: Patients with POLE-mutated early-stage EC undergo observation on study.

COHORT A2: Patients with higher-risk POLE-mutated EC undergo observation or external beam radiation therapy (EBRT) and/or vaginal brachytherapy over 3-5 fractions.

SUB-STUDY B: Patients with p53 wildtype/NSMP ER+ EC undergo observation or vaginal brachytherapy over 3-5 fractions.

All patients undergo chest x-ray and computed tomography (CT) or magnetic resonance imaging (MRI) or positron emission tomography (PET)/CT scans during screening and as clinically indicated throughout the trial.

After completion of study treatment, patients are followed up at 3 and 6 months, then every 6 months for 3 years, and then every year.

Eligibility criteria: Inclusion Criteria:

* Patients must have had surgery consisting of hysterectomy (total abdominal, laparoscopic or robotic-assisted) and bilateral salpingo-oophorectomy. Lymph node dissection can be performed as per institutional standards (sentinel or full lymphadenectomy). 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
* Patients' age must be \>= 18 years
* Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate. A similar process must be followed for sites outside of Canada as per their respective cooperative group's procedures
* 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. The baseline assessment must be completed within required timelines, prior to enrollment. Inability (lack of comprehension in English or French, or other equivalent reason such as cognitive issues or lack of competency) to complete the questionnaires will not make the patient ineligible for the study. However, ability but unwillingness to complete the questionnaires will make the patient ineligible
* Patients must be accessible for treatment and follow-up. Patients enrolled on this trial must be treated and followed at the participating centre. This implies there must be reasonable geographical limits placed on patients being considered for this trial. The patient's city of residence may be required to verify their geographical proximity. (Call the CCTG office (613-533-6430) if questions arise regarding the interpretation of this criterion.) Investigators must assure themselves the patients enrolled on this trial will be available for complete documentation of the treatment, adverse events, and follow-up
* Patients must agree to return to their primary care facility for any adverse events which may occur through the course of the trial
* Protocol treatment is to begin within 10 weeks of hysterectomy/bilateral salpingo-oophorectomy
* SUB-STUDY A: Patients with endometrial carcinoma (endometrioid, serous, clear cell, un-/dedifferentiated, carcinosarcoma, mixed), must have one of the following combinations of International Federation of Gynecology and Obstetrics (FIGO) stage, grade, and lymphovascular invasion (LVI):

  * Cohort A1:

    * Stage IA (not confined to polyp), grade 3, pN0, with or without LVI (Pelvic lymph node surgical assessment (sentinel or full lymphadenectomy) is required for grade 3 or stage II. Para-aortic lymphadenectomy is not mandated.)
    * Stage IB, grade 1 or 2, pNx/N0, with or without LVI
    * Stage IB, grade 3, pN0, without substantial LVI (Pelvic lymph node surgical assessment (sentinel or full lymphadenectomy) is required for grade 3 or stage II. Para-aortic lymphadenectomy is not mandated.)
    * Stage II (microscopic), grade 1 or 2, pN0, without substantial LVI (Pelvic lymph node surgical assessment (sentinel or full lymphadenectomy) is required for grade 3 or stage II. Para-aortic lymphadenectomy is not mandated.) (Substantial LVI is defined as \>= 3 foci per College of American Pathologists' reporting guideline)
  * Cohort A2:

    * Stage IA (not confined to polyp), grade 3, pNx, with or without LVI
    * Stage IB, grade 3, pNx, with or without LVI
    * Stage IB, grade 3, pN0, with substantial LVI (Substantial LVI is defined as \>= 3 foci per College of American Pathologists' reporting guideline)
    * Stage II (microscopic), grade 1 or 2, pNx, with or without LVI
    * Stage II (microscopic), grade 1 or 2, pN0, with substantial LVIƒõ
    * Stage II (microscopic), grade 3, pNx/N0, with or without LVI
    * Stage II non-microscopic, any grade, pNx/N0, with or without LVI
    * Stage III, any grade, pNx/N0-2, with or without LVI
    * Substantial LVI is defined as .3 foci per College of American Pathologists¡¦ reporting guideline
* SUB-STUDY A: Patients must have a molecular classification of POLE mutation.

  * Note: patients in Cohort A2 should have a known POLE pathogenic mutation prior to consenting
* SUB-STUDY B: Patients with endometrial carcinoma (endometrioid only), must have one of the following combinations of FIGO stage, grade, and lymphovascular invasion (LVI):

  * Stage IA (not confined to polyp), grade 3, pN0, with or without LVI (Pelvic lymph node surgical assessment \[sentinel or full lymphadenectomy\] is required for grade 3 or stage II. Para-aortic lymphadenectomy is not mandated) (Substantial LVI is defined as \>= 3 foci per College of American Pathologists' reporting guideline)
  * Stage IB, grade 1 or 2, pNx/N0, with or without LVI
  * Stage IB, grade 3, pN0, without substantial LVI (Pelvic lymph node surgical assessment \[sentinel or full lymphadenectomy\] is required for grade 3 or stage II. Para-aortic lymphadenectomy is not mandated) (Substantial LVI is defined as \>= 3 foci per College of American Pathologists' reporting guideline)
  * Stage II (microscopic), grade 1 or 2, pN0\*, without substantial LVI (Pelvic lymph node surgical assessment \[sentinel or full lymphadenectomy\] is required for grade 3 or stage II. Para-aortic lymphadenectomy is not mandated) (Substantial LVI is defined as \>= 3 foci per College of American Pathologists' reporting guideline)
* SUB-STUDY B: Patients must have molecular classification of p53wt/NSMP (based on normal p53 IHC, and absence of pathogenic POLE mutation or MMR deficiency)
* SUB-STUDY B: Estrogen receptor positive (\> 10% of the tumour with positive nuclear staining) on IHC

Exclusion Criteria:

* Prior neoadjuvant chemotherapy for current endometrial cancer diagnosis
* Prior pelvic radiation
* Patients with a history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid 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)
* SUB-STUDY A: Isolated tumour cell(s) identified in lymph node(s) for patients in Cohort A1
* SUB-STUDY B: Abnormal p53 and/or mismatch repair deficiency on immunohistochemistry without pathogenic POLE mutation.

  * Abnormal p53 can also be determined by TP53 mutations found on DNA testing.
* SUB-STUDY B: p53wt/NSMP endometrial carcinoma with a MELF (microcystic, elongated and fragmented) pattern of myoinvasion and/or substantial lymphovascular invasion
* SUB-STUDY B: Stage IA (not confined to polyp), grade 3, pN0, with substantial LVI. Stage IB, grade 1 or 2, pNx/N0, with substantial LVI
* SUB-STUDY B: Isolated tumour cell(s) identified in lymph node(s)

Primary outcomes:
measure: Time to pelvic recurrence
timeFrame: Time from enrollment to the time of recurrent disease within the pelvis (including the vagina), assessed up to 2 years
measure: Time to isolated vaginal recurrence
timeFrame: Time from enrollment to the time of histologic confirmation of vaginal recurrence, assessed up to 2 years
measure: Time to para-aortic recurrence
timeFrame: Time from enrollment to the time of radiological and/or histologic confirmation of para-aortic recurrence (i.e. nodal recurrence at/above L5/S1 and below the renal hilum), whichever occurs first, assessed up to 2 years
measure: Time to distant metastasis
timeFrame: Time from enrollment to the time of radiological and/or histologic confirmation of para-aortic recurrence (i.e. nodal recurrence at/above L5/S1 and below the renal hilum), whichever occurs first, assessed up to 2 years
measure: Recurrence-free survival
timeFrame: Time from enrollment to the time of endometrial cancer recurrence or death, whichever occurs first, assessed up to 2 years
measure: Endometrial cancer-specific survival
timeFrame: Time from enrollment to the time of death from endometrial cancer, assessed up to 2 years
measure: Overall survival
timeFrame: Time from enrollment to the time of death from any cause, assessed up to 2 years
measure: Quality of life (QOL)
timeFrame: Up to 2 years
measure: Health economics
timeFrame: Up to 2 years
measure: Decisional conflict
timeFrame: Up to 2 years
measure: Fear of recurrence
timeFrame: Up to 2 years
measure: Incidence of adverse events
timeFrame: Up to 2 years
measure: Variability in adjuvant treatment
timeFrame: Up to 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Alaska Women's Cancer Care
state: Alaska
city: Tucson
country: United States
facility: University of Arizona Cancer Center-Orange Grove Campus
state: Arizona
city: Tucson
country: United States
facility: Banner University Medical Center - Tucson
state: Arizona
city: Tucson
country: United States
facility: University of Arizona Cancer Center-North Campus
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: N. Venice
country: United States
facility: Sarasota Memorial Hospital-Venice
state: Florida
city: Sarasota
country: United States
facility: Florida Cancer Specialists - Sarasota Downtown
state: Florida
city: Sarasota
country: United States
facility: First Physicians Group-Sarasota
state: Florida
city: Sarasota
country: United States
facility: Sarasota Memorial Hospital
state: Florida
city: Sarasota
country: United States
facility: Sarasota Memorial Health Care Center at University Parkway
state: Florida
city: Venice
country: United States
facility: Florida Cancer Specialists - Venice Pinebrook
state: Florida
city: Atlanta
country: United States
facility: Grady Health System
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital Midtown
state: Georgia
city: Atlanta
country: United States
facility: Piedmont Hospital
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital/Winship Cancer Institute
state: Georgia
city: Atlanta
country: United States
facility: Emory Saint Joseph's Hospital
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Springfield
country: United States
facility: Springfield Memorial Hospital
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: Baltimore
country: United States
facility: Sinai Hospital of Baltimore
state: Maryland
city: Worcester
country: United States
facility: UMass Memorial Medical Center - Memorial Division
state: Massachusetts
city: Billings
country: United States
facility: Saint Vincent Frontier Cancer Center
state: Montana
city: Billings
country: United States
facility: Intermountain Health West End Clinic
state: Montana
city: Sewell
country: United States
facility: Sidney Kimmel Cancer Center Washington Township
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
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 Upstate Medical University
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 Women's Cancer Care Raleigh
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Portland
country: United States
facility: Providence Saint Vincent Medical Center
state: Oregon
city: Hershey
country: United States
facility: Penn State Milton S Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
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: Conroe
country: United States
facility: MD Anderson in The Woodlands
state: Texas
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
city: Houston
country: United States
facility: MD Anderson West Houston
state: Texas
city: League City
country: United States
facility: MD Anderson League City
state: Texas
city: Sugar Land
country: United States
facility: MD Anderson in Sugar Land
state: Texas
city: Farmington
country: United States
facility: Farmington Health Center
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah Sugarhouse Health Center
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/Massey Cancer Center
state: Virginia
city: Edmonds
country: United States
facility: Swedish Cancer Institute-Edmonds
state: Washington
city: Issaquah
country: United States
facility: Swedish Cancer Institute-Issaquah
state: Washington
city: Seattle
country: United States
facility: Swedish Medical Center-First Hill
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: San Juan
country: Puerto Rico
facility: Centro Comprensivo de Cancer de UPR
Study officials:
affiliation: NRG Oncology
name: Matthew A Powell
role: PRINCIPAL_INVESTIGATOR
References: