Clinical trial NCT04159155: A Study of Various Treatments in Serous or p53 Abnormal Endometrial Cancer
Official title: Canadian Multi-arm Multi-stage Randomized Controlled Trial Assessing Front Line and Maintenance Treatment in Serous or p53 Mutant Endometrial Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Endometrial Carcinoma
P53 Mutation
Serous Carcinoma
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2019-11-12
Enrollment: 267
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is an umbrella, two-arm, multi-stage, phase II trial. The purpose of the trial in the early stage cohort is to determine if EBRT improves disease free survival (defined as the time from random assignment to disease recurrence or death from any cause) compared to vaginal brachytherapy after chemotherapy in women with serous or p53 aberrant endometrial cancer. The purpose of the trial in the advanced stage cohort is to determine if the maintenance with experimental treatment increases progression free survival, defined as the time from random assignment to disease progression or death from any cause.

Detailed description: SC represents a rare and aggressive histologic subtype of endometrial cancer, associated with a poor prognosis. Moreover, there are marked molecular differences between EC and SC, showing the need to separate clinical trials to develop the personalized treatment paradigms that have improved outcomes in other tumor types, such as breast and lung cancer. Given the absence of consensus between pathologists on the diagnosis of SC, this trial will also incorporate a molecular marker, p53abd.

Several studies have been done in early stage endometrial cancer including diverse histologies, stages and molecular characteristics. Due to the heterogeneity of the patients, there is a lack of knowledge on the best treatment strategy. Even in cases where disease is apparently confined to the endometrium, the rate of recurrence is high. The role of radiation therapy in the management of this disease, with a high propensity for distant failures, remains elusive.

Furthermore, women with endometrial cancer often have multiple comorbidities, needing to optimize the treatment strategies and toxicities. It then results crucial to identify a strategy that is effective and results in limited toxicity.

Advanced or recurrent SC has a poor prognosis. There are no maintenance strategies currently approved for endometrial cancer and this is under investigation.

Eligibility criteria: Inclusion Criteria:

* Patients with pure serous endometrial carcinoma will be included. Other histotypes (endometrioid and clear cell) with abnormal/mutant-type p53 is acceptable.
* Local TP53 results must be available for Central review.
* Patients diagnosed with stage I, II tumors will be enrolled in the early stage cohort.
* Patients suitable for an optimal surgery.
* Eastern Cooperative Group (ECOG) performance status ≤ 2 (Karnofsky ≥60%).
* Life expectancy of greater than 3 months.
* Patients must have archival tissue available. If no tissue is available, tumor biopsy will be mandatory.
* Ability to understand and willing to sign a written informed consent document.
* Within 8 days of the proposed start of treatment, patients must have normal organ and marrow function.
* Women of child-bearing potential must agree to use effective contraceptive methods prior to study entry, during study participation, and for at least 30 days after the last administration of study medication.

Exclusion Criteria:

* Any other condition that would contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures.
* Mixed serous tumors without p53 aberration or with only subclonal p53 aberration
* Endometrial carcinosarcoma
* Patients being treated with radiotherapy within 4 weeks, or palliative radiotherapy encompassing \>20% of the bone marrow within 1 week of starting study treatment.
* Patients who are receiving any other investigational agents.
* Participant has leptomeningeal disease, carcinomatous meningitis, symptomatic brain metastases, or radiologic signs of CNS hemorrhage. Note: Participants with asymptomatic brain metastases (i.e. off corticosteroids and anticonvulsants for at least 7 days) are permitted.
* Patients with evidence of fistula will be excluded.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in study.
* Uncontrolled inter-current illness that would limit compliance with study requirements.
* Pregnant women are excluded.
* Known HIV-positive patients on antiretroviral therapy or active Hepatitis B or C are ineligible.
* Patients with a history of other malignancy ≤ 2 years prior to registration, with exceptions.

Primary outcomes:
measure: Disease Free Survival Rate
timeFrame: 3 years
Secondary outcomes:
measure: Overall Survival Rate
timeFrame: 5 years
measure: Number Adverse Events Experienced
timeFrame: 5 years
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
Study officials:
affiliation: Princess Margaret Cancer Centre
name: Amit Oza, MD
role: PRINCIPAL_INVESTIGATOR
References: