The purpose of this single arm, open label study is to evaluate the feasibility of
pembrolizumab combined with radiation administered to the upper part of the vagina (vaginal
cuff brachytherapy) followed by three cycles of pembrolizumab and chemotherapy in patients
with endometrial cancer.
Before the patient begins the study:
Endometrial cancer is commonly treated with surgery. The patient must have already had
surgery including hysterectomy (removal of the uterus) prior to being considered eligible for
this study. The surgery may also include removal of the ovaries, and removal of pelvic and
para-aortic lymph nodes. Following the surgery, the doctor will identify if the patient has
factors related to the cancer which places the patient at a greater risk for the cancer
returning.
Prior to participating in this study there are exams, tests or procedures to find out if the
patient can be treated in the study. Most are part of regular cancer care. Tumor tissue will
need to be collected for study tests to see if the patient is eligible for to take part on
the study.
TREATMENT If the patient is eligible, pembrolizumab will be given 7 days before radiation
therapy. After radiation therapy, three cycles of pembrolizumab and chemotherapy will be
given.
Study participation will be up to two years.
Inclusion Criteria:
1. All patients must have undergone hysterectomy. Bilateral salpingooophorectomy is
strongly encouraged but not mandatory.
2. Pelvic and para-aortic lymphadenectomy are optional, but strongly encouraged.
3. If either a bilateral salpingo-oophorectomy (BSO) or nodal sampling was not performed,
post-operative pre-treatment CT/MRI is required and must not demonstrate evidence
suggestive of metastatic disease (adnexa, nodes, intraperitoneal disease).
Post-operative, pre-treatment CT/MRI must be performed if a BSO and/or lymphnode
sampling was not performed.
4. Tissue from an archival sample or newly obtained core or excisional biopsy of a tumor
lesion within 10 weeks confirming diagnosis.
5. All patients will be staged according to the FIGO 2009 staging system and with
endometrial carcinoma (endometrioid types) confined to the corpus uteri or with
endocervical glandular involvement fitting one of the following high-intermediate risk
factor categories:
- age ≥18 years with 3 risk factors
- Risk factors:
1. Grade 2 or 3 tumor, (+) lymphovascular space invasion, outer ½ myometrial
invasion. Patients with these risk criteria may be enrolled with either
positive or negative cytology.
2. Patients with Stage II endometrial carcinoma (any histology) with cervical
stromal invasion (occult or gross involvement), with or without
high-intermediate risk factors.
3. Patients with serous or clear cell histology (with or without other
high-intermediate risk factors) are eligible provided the disease is Stage I
or II (with or without cervical stromal invasion or endocervical glandular
involvement). Eligibility for clear cell and serous histology is not based
on presence of lymphovascular space invasion or depth of invasion.
6. Patients must have ECOG performance status 0 or 1.
7. The participant (or legally acceptable representative if applicable) provides written
informed consent for the trial and authorization permitting release of personal health
information.
8. Neuropathy (sensory and motor) ≤ Grade 1.
9. Have adequate organ function as defined per Protocol.
Exclusion Criteria:
1. Patients with recurrent disease.
2. Greater than 12 weeks elapsed from surgery to enrollment
3. Patients have prior pelvic or abdominal radiation therapy
4. Known hypersensitivity to any component of study treatments that resulted in drug
discontinuation
5. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with
an agent directed to another stimulatory or co-inhibitory T-cell receptor
6. Has received prior systemic anti-cancer therapy including investigational agents
within 4 weeks [could consider shorter interval for kinase inhibitors or other short
half-life drugs] prior to allocation.
7. Has received prior radiotherapy within 2 weeks of start of study treatment.
Participants must have recovered from all radiation-related toxicities, not require
corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted
for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
8. Has received a live vaccine within 30 days prior to the first dose of study drug.
9. Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 4 weeks prior to the first dose of
study treatment.
10. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior to the first dose of study drug.
11. Has a known additional malignancy that is progressing or has required active treatment
within the past 3 years. Note: Participants with basal cell carcinoma of the skin,
squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma,
cervical cancer in situ) that have undergone potentially curative therapy are not
excluded.
12. Has known active CNS metastases and/or carcinomatous meningitis.
13. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
14. Has active autoimmune disease that has required systemic treatment in the past 2 years
(i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment.
15. Has a history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis.
16. Has an active infection requiring systemic therapy. This excludes grade 2 urinary
tract infections or grade 1-2 skin infections.
17. Has a known history of Human Immunodeficiency Virus (HIV).
18. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]
reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is
detected) infection.
19. Has a known history of active TB (Bacillus Tuberculosis).
20. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the study, interfere with the subject's
participation for the full duration of the study, or is not in the best interest of
the subject to participate, in the opinion of the treating investigator.
21. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
22. Is pregnant or breastfeeding
