Trial Title:
Tailoring Therapy in Post-surgical Patients With Low-risk Endometrial Cancer
NCT ID:
NCT06388018
Condition:
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
Conditions: Official terms:
Sarcoma
Endometrial Neoplasms
Sarcoma, Endometrial Stromal
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Other
Intervention name:
Clinical Observation
Description:
Undergo observation
Arm group label:
Cohort A1
Arm group label:
Cohort A2
Arm group label:
Sub-study B
Other name:
observation
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT or PET/CT
Arm group label:
Cohort A1
Arm group label:
Cohort A2
Arm group label:
Sub-study B
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
Computerized Tomography (CT) scan
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Radiation
Intervention name:
External Beam Radiation Therapy
Description:
Undergo EBRT
Arm group label:
Cohort A2
Other name:
Definitive Radiation Therapy
Other name:
EBRT
Other name:
External Beam Radiation
Other name:
External Beam Radiotherapy
Other name:
External Beam Radiotherapy (conventional)
Other name:
External Beam RT
Other name:
external radiation
Other name:
External Radiation Therapy
Other name:
external-beam radiation
Other name:
Radiation, External Beam
Other name:
Teleradiotherapy
Other name:
Teletherapy
Other name:
Teletherapy Radiation
Intervention type:
Procedure
Intervention name:
High-Dose-Rate Vaginal Brachytherapy
Description:
Undergo vaginal brachytherapy
Arm group label:
Cohort A2
Arm group label:
Sub-study B
Other name:
HDR-IVB
Other name:
High-Dose-Rate Intra-Vaginal Brachytherapy
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Cohort A1
Arm group label:
Cohort A2
Arm group label:
Sub-study B
Other name:
Magnetic Resonance
Other name:
Magnetic Resonance Imaging (MRI)
Other name:
Magnetic resonance imaging (procedure)
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
MRIs
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Other name:
sMRI
Other name:
Structural MRI
Intervention type:
Procedure
Intervention name:
Positron Emission Tomography
Description:
Undergo PET/CT
Arm group label:
Cohort A1
Arm group label:
Cohort A2
Arm group label:
Sub-study B
Other name:
Medical Imaging, Positron Emission Tomography
Other name:
PET
Other name:
PET Scan
Other name:
Positron emission tomography (procedure)
Other name:
Positron Emission Tomography Scan
Other name:
Positron-Emission Tomography
Other name:
proton magnetic resonance spectroscopic imaging
Other name:
PT
Intervention type:
Other
Intervention name:
Questionnaire Administration
Description:
Ancillary studies
Arm group label:
Cohort A1
Arm group label:
Cohort A2
Arm group label:
Sub-study B
Intervention type:
Procedure
Intervention name:
X-Ray Imaging
Description:
Undergo x-ray imaging
Arm group label:
Cohort A1
Arm group label:
Cohort A2
Arm group label:
Sub-study B
Other name:
Conventional X-Ray
Other name:
Diagnostic Radiology
Other name:
Medical Imaging, X-Ray
Other name:
Plain film radiographs
Other name:
Radiographic Imaging
Other name:
Radiographic imaging procedure (procedure)
Other name:
Radiography
Other name:
RG
Other name:
Static X-Ray
Other name:
X-Ray
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.
Criteria for 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)
Gender:
Female
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Women and Infants Hospital
Address:
City:
Providence
Zip:
02905
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
401-274-1122
Investigator:
Last name:
Matthew T. Oliver
Email:
Principal Investigator
Start date:
January 16, 2025
Completion date:
January 16, 2027
Lead sponsor:
Agency:
NRG Oncology
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Collaborator:
Agency:
Canadian Cancer Trials Group (CCTG)
Agency class:
Other
Source:
NRG Oncology
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06388018
