Recurrent Endometrial Cancer
Conditions
Brief summary
The purpose of this study is to determine the efficacy and safety of Pembrolizumab in combination with Lenvatinib in recurrent, mismatch repair-proficient endometrial cancer after failure of first-line therapy with a platinum-based doublet chemotherapy and immunotherapy.
Interventions
DRUGPembrolizumab
Participants will receive 200mg of Pembrolizumab intravenously on Day 1 of every 21 day cycle, as per standard of care and as per institutional guidelines.
DRUGLenvatinib
Participants will self-administer Lenvatinib orally at a daily dose of 20mg or every 21 day cycle, as per standard of care and as per institutional guidelines.
Sponsors
University of Miami
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically confirmed recurrent endometrial carcinoma, including serous, endometrioid, carcinosarcoma, clear cell subtypes, with measurable disease per RECIST 1.1 criteria. 2. Mismatch repair (MMR) proficient status confirmed by IHC (Immunohistochemistry) or molecular testing. 3. Patients must have failed first-line therapy with platinum based doublet with prior immunotherapy. 4. Patient must have completed next-generation sequencing on either primary or recurrent tumor. 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 3. 6. Age ≥ 18 years. 7. Female participants must be of non-childbearing potential or for females of child bearing potential (FOCBPs), must agree to use contraception as described in Section 5.6. FOCBPs must not be pregnant or breastfeeding. 8. At least one measurable lesion according to RECIST 1.1. 9. Adequate organ function, including: * Hemoglobin ≥ 8 g/dL (blood transfusions are permitted) * Absolute neutrophil count ≥ 1000 * Platelet count ≥ 100 x 10⁹/L * Glomerular filtration rate (GFR) ≥ 30 mL/min * Bilirubin ≤ 1.5 x ULN (upper limit of normal) 10. Written informed consent obtained from the patient. 11. At least 3 weeks must have elapsed from any prior therapy
Exclusion criteria
1. Uterine sarcoma 2. Active central nervous system metastases or leptomeningeal disease. 3. History of severe allergic reactions to pembrolizumab, lenvatinib, or any components of the formulations. 4. Active autoimmune disease requiring chronic systemic steroids for \> 3 months in the last 6 months prior to enrollment. 5. Pregnancy or breastfeeding at the time of enrollment. 6. Previous treatment with lenvatinib or other VEGFR inhibitors. 7. Concurrent treatment with other investigational drugs or anti-cancer therapies except for adjuvant hormonal therapy for breast cancer. 8. Uncontrolled concurrent illness, such as active infections that could interfere with study participation. 9. Blood pressure \>160 systolic or \>110 diastolic averaged over last 3 documented measurements. 10. History of significant cardiovascular events within 12 months prior to enrollment, including myocardial infarction, unstable angina, or congestive heart failure (NYHA Class III or IV). 11. History of organ transplant or immune suppressive therapy that would interfere with the efficacy or safety of the investigational drugs. 12. Other malignancies within the past 2 years except for non-melanoma skin cancer.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Benefit Rate | Baseline, Up to 18 weeks | Clinical benefit rate (CBR) is defined as the proportion of participants achieving complete response (CR), partial response (PR) or sustained stable disease (SD), as the best response as assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Up to 26 months | Objective Response Rate (ORR) is defined as the proportion of participants achieving complete response (CR) or partial response (PR) as the best response assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. |
| Progression-Free Survival (PFS) | Up to 26 months | Progression-Free Survival (PFS) is the elapsed time in months from date of treatment initiation until progression or death from any cause. Patients who are alive and without documented disease progression will be censored at the date of their last disease assessment. |
| Overall Survival (OS) | Up to 26 months | Overall Survival (OS) is the elapsed time in months from date of treatment initiation until death from any cause. Alive patients will be censored at the last date known to be alive. |
| Duration of Response (DOR) | Up to 26 months | Duration of Response (DOR) is the elapsed time in months from date of first documentation of complete response (CR) or partial response (PR) until first documentation of progression or death from any cause for responders. Patients who are alive and without documented disease progression will be censored at the date of their last disease assessment. |
| Number of Participants Experiencing Treatment-Related Toxicity: Serious Adverse Events (SAEs) | Up to 26 months | The safety and tolerability of combination Pembrolizumab and Lenvatinib therapy will be reported as the number of participants experiencing treatment-related serious adverse events (SAEs). SAEs will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5. |
| Number of Participants Experiencing Treatment-Related Toxicity: Adverse Events (AEs) | Up to 26 months | The safety and tolerability of combination Pembrolizumab and Lenvatinib therapy will be reported as the number of participants experiencing treatment-related adverse events (AEs). AEs will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5. |
| Health-Related Quality of Life Scores: Patient-Reported Outcomes via EORTC QLQ-17 | Up to 26 months | Participant quality of life will be assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 17 (EORTC QLQ-17), a validated 17-item questionnaire measuring global health status and functional domains relevant to cancer patients. Items are scored using standardized Likert scales and converted to 0-100 domain scores according to EORTC scoring guidelines. Higher scores indicate better functioning and overall quality of life. |
| Health-Related Quality of Life Scores: Patient-Reported Social Isolation via Social Provisions Scale - 10 items (SPS-10) | Up to 26 months | Social isolation will be measured using the 10-item short form of the Social Provisions Scale, a validated instrument assessing perceived social support and relational connectedness. Each item is rated on a 4-point Likert scale (1 = Strongly Disagree, 2 = Disagree, 3= Agree, 4 = Strongly Agree), yielding a total score ranging from 10 to 40, with higher scores indicating greater perceived social support (lower social isolation). |
| Health-Related Quality of Life Scores: Patient-Reported Social Needs via Health Leads 10-Item Screening Tool | Up to 26 months | Unmet social needs will be assessed using the 10-item Health Leads Social Needs Screening Tool, a validated questionnaire identifying needs such as food insecurity, housing instability, transportation barriers, and utility challenges. Each item is coded as 1 (unmet need present) or 0 (no unmet need). Total scores represent the count of unmet social needs (range 0-10), with higher scores indicating greater social needs burden. |
Countries
United States
Contacts
CONTACTNavya Nair, MD, MPH
CONTACTAbdulrahman Sinno, MD
PRINCIPAL_INVESTIGATORNavya Nair, MD, MPH
University of Miami
Outcome results
None listed