In the RAINBO POLEmut-BLUE trial, omission of adjuvant therapy will be investigated in very low risk disease and de-escalation of treatment (observation or radiotherapy, but not chemoradiation) in low risk disease.
ID
Source
Brief title
Condition
- Reproductive neoplasms female malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
3-year pelvic recurrence
Secondary outcome
5-year pelvic recurrence, 3- and 5-year RFS, decisional conflict, and fear of
recurrence. 3- and 5-year vaginal recurrence-free survival, distant
recurrence-free survival, endometrial cancer-specific survival, overall
survival, treatment-related toxicity (using the Common Terminology Criteria for
Adverse Events (CTCAE) version 5) and health-related quality of life (using the
common and endometrial cancer European Organization for Research and Treatment
of Cancer (EORTC) Quality of Life Questionnaires C30 and EN24).
Background summary
POLEmut endometrial cancer is the least common molecular class of endometrial
cancer (~10%), and excellent patient outcomes are consistently demonstrated
with this tumor feature, regardless of adjuvant therapy. POLEmut endometrial
cancer is characterized by
a high tumor mutational burden and has one of the 11 pathogenic mutations in
the exonuclease domain of the POLE gene.(Leon et al. J Pathol 2020) Endometrial
cancer with non-pathogenic POLE mutations has been shown to have significantly
more disease-related
events and is often associated with mismatch-repair deficiency.(McAlpine et al.
2021, Cancer) A meta-analysis of 294 patients with pathogenic POLE mutations
showed that 4.1% had disease recurrence or progression and only 1.0% died due
to their
disease.(McAlpine et al. 2021, Cancer) There was no apparent benefit in
clinical outcomes from receiving adjuvant therapy.(McAlpine et al. 2021,
Cancer) An in vitro study showed that pathogenic POLE mutations did not
increase sensitivity to radiotherapy or chemotherapeutics.(van Gool et al. 2015
CCR) Women with high-risk POLEmut endometrial cancer included in PORTEC-3 had
excellent outcomes regardless of the addition of chemotherapy (5-year RFS 100%
vs 97%, p=0.64).(Leon et al. JCO 2020) A recent Danish population-based study
confirmed that the prognosis of women with POLEmut endometrial cancer is
excellent even in the absence of adjuvant treatment.(Leon et al. Gyn Onc 2023)
These data support a phase II clinical trial on treatment de-escalation for
POLEmut endometrial cancer.
Study objective
In the RAINBO POLEmut-BLUE trial, omission of adjuvant therapy will be
investigated in very low risk disease and de-escalation of treatment
(observation or radiotherapy, but not chemoradiation) in low risk disease.
Study design
The POLEmut-BLUE trial is a prospective phase II clinical that will recruit 120
patients with select stage I-II POLEmut endometrial cancer in the main *very
low risk* study cohort. A 3-year pelvic recurrence rate of 1% (upper 95% CI
2.4%) is assumed. If the upper 95% CI is <5%, it will be concluded that no
adjuvant therapy has an acceptable low risk of pelvic recurrence (one-sided
α=0.05). Patients will be recruited over 36 months with 36 months of additional
follow-up. In addition, patients with *low risk* POLEmut endometrial cancer
will be accrued into an exploratory cohort (approximately 25 patients) for
descriptive analysis.
Study burden and risks
Given the experience of previous studies with tumors with a POLE mutation, it
is expected that patients will benefit from de-escalation of adjuvant
treatment. This is not entirely certain. There is an extremely small chance
that the cancer will come back locally due to the omission of additional
treatment. This risk is estimated at 2-3%. Risks of up to 5% are considered
acceptable. The study will be terminated if the risk is 5% or more.
The expectation is that the chance of survival will be the same for all women,
and that the chance that the disease will not recur is very high. For the few
women whose disease recurs locally (in the pelvis), external and internal
radiation can still be given. For the very small group of women whose cancer
has returned elsewhere in the body, further treatment depends very much on the
situation.
The risk classification of this study is estimated to be moderate.
Albinusdreef 2
Leiden 2333 ZA
NL
Albinusdreef 2
Leiden 2333 ZA
NL
Listed location countries
Age
Inclusion criteria
Protocol page 9/10
- 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.
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) (see the radiology timeline outlined in Section 5).
Design
Recruitment
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT05640999 |
| CCMO | NL84566.058.23 |