A Study of Various Treatments in Serous or p53 Abnormal Endometrial Cancer

NCT ID: NCT04159155

Last Updated: 2025-08-12

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-17
• Study Completion Date: 2025-05-26

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.

Conditions

Endometrial Carcinoma; P53 Mutation; Serous Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Early Stage Cohort - Arm A

Pelvic EBRT at 45Gy in 25 fractions, in 1.8Gy fractions daily, 5 days per week

Group Type: EXPERIMENTAL

External Beam Radiation

Intervention Type: RADIATION

Radiation therapy given outside the patient to a particular part of the body.

Early Stage Cohort - Arm B1

Vaginal high-dose rate brachytherapy 21 Gy in 3 fractions, prescribed to 5mm (i.e. 100% isodose at 5mm) from the cylinder/applicator surface and top along the upper third to half of the vagina (minimum 3cm, maximum 4cm).

Group Type: EXPERIMENTAL

Vaginal high-dose rate brachytherapy

Intervention Type: RADIATION

Internal radiation to the vagina

Advanced Stage Cohort Arm C

Observation

Group Type: ACTIVE_COMPARATOR

Observation - no drugs

Intervention Type: OTHER

Observation

Advanced Stage Cohort Arm D1

Investigational agent (niraparib), orally, at a dose of 200 mg, or 300 mg, once daily, based on baseline platelet count and weight.

Group Type: EXPERIMENTAL

Niraparib

Intervention Type: DRUG

Oral drug

Interventions

External Beam Radiation

Radiation therapy given outside the patient to a particular part of the body.

Intervention Type: RADIATION

Niraparib

Oral drug

Intervention Type: DRUG

Vaginal high-dose rate brachytherapy

Internal radiation to the vagina

Intervention Type: RADIATION

Observation - no drugs

Observation

Intervention Type: OTHER

Other Intervention Names

Zejula

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Amit Oza, MD

Role: PRINCIPAL_INVESTIGATOR

Princess Margaret Cancer Centre

Locations

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Countries

Canada

Other Identifiers

CAPCR 19-6178

Identifier Type: OTHER

Identifier Source: secondary_id

CAN-STAMP

Identifier Type: -

Identifier Source: org_study_id