Recurrent Endometrial CarcinomaPhase 1NCT05603910
Phase 1 Clinical Trial of Lenvatinib, Pembrolizumab and Hypofractionated Pelvic Radiation Therapy for pMMR Recurrent/Unresectable Endometrial Carcinoma
A Phase 1 study testing Lenvatinib, Pembrolizumab and Hypofractionated External Beam Radiation Therapy in people with Recurrent Endometrial Carcinoma and Unresectable Endometrial Carcinoma, run by Aaron Wolfson at 1 site in United States.
Trial summary
The purpose of this research study is to see if it is feasible to combine a fixed dose of pembrolizumab and a daily dose of oral lenvatinib, along with daily treatments of an abbreviated course of pelvic external beam radiation therapy, to support cancer cells in multiplying and spreading to other body sites. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Recurrent Endometrial Carcinoma, Unresectable Endometrial Carcinoma
- What is being tested?
- Lenvatinib, Pembrolizumab and Hypofractionated External Beam Radiation Therapy
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Apr 2023to 15 Apr 2034
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Biopsy-proven recurrent pMMR EC following surgery alone or de novo unresectable pMMR EC for whom EBRT has been determined as an appropriate therapeutic approach. Eligible tumor histologies include the following: endometrioid adenocarcinoma, adenocarcinoma with squamous differentiation, mucinous, mixed carcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, serous adenocarcinoma, and uterine carcinosarcoma histologies as determined by tissue from an archival sample or newly obtained core or excisional biopsy of a tumor lesion. For patients with recurrent disease greater than 12 months (>12 months), a fresh biopsy must be obtained.
- Measurable disease of at least 1.0 cm in size defined by RECIST 1.1 on imaging studies with at least one (1) site located in the pelvis and/or vagina without any foci of extra-pelvic disease (including the para-aortic region or inguinal-femoral lymph nodes).
- Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (Karnofsky score ≥50).
- Patients must have pMMR tumor subtype(s).
- Patients must have normal organ and marrow function as defined below:
- Absolute neutrophil count (ANC) ≥1,500 cells/mm³
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- Platelets ≥100,000 cells/mm³
- Hemoglobin ≥9.0 g/dL
- Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or creatine clearance (CrCl) ≥ 40 mL/min or Measured or calculated a creatinine clearance glomerular filtration rate (GFR) can also be used in place of creatinine
- Serum total bilirubin <1.0 ULN
- Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT) and alanine transaminase (ALT) serum glutamic-pyruvic transaminase (SGPT) Aminotransferase (AST and ALT) ≤ 2.5 x ULN or 5 X ULN for patients with liver metastases
- Albumin ≥2.5 mg/dL CrCl should be calculated per institutional standard.
- Female participants of childbearing potential (those who have not been surgically sterilized or have not been without menses for >1 year) should be willing to use 2 methods of birth control at the same time or be surgically sterile or abstain from heterosexual activity for the course of the study and for at least 120 days after the last study dose.
- Ability to understand and the willingness to sign a written informed consent document.
- Prior treatment with lenvatinib, anti-programmed cell death protein 1 (anti-PD-1), anti-Programmed death-ligand 1 (anti-PD-L1) , or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways is allowed provided that the participant has not received any of these treatments within three weeks (+/- 3 days) of the first dose of study treatment.
- Women age ≥18 years old.
- Patients who have received prior adjuvant vaginal high dose rate (HDR) brachytherapy without EBRT following hysterectomy will be eligible as long as the cumulative Equivalent Dose at 2-Gy (EqD2) for external beam pelvic dose and vaginal HDR brachytherapy dose for the rectum and sigmoid colon is at most 70 Gy, for bowel at most 65 Gy, and for bladder at most 90 Gy.
Who cannot join
- Patients who are currently in or have participated in a study of an investigational agent or used an investigational device within 4 weeks of the first dose of study treatment.
- Patients with Mismatch repair deficient (dMMR) and endometrial carcinomas.
- Patients with dMMR and uterine carcinosarcomas.
- Patients with known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- EXCEPTION: Patients with previously treated brain metastases, including receiving prior brain irradiation, may participate provided they are stable (without evidence of progression by imaging for at least 3 months prior to the first dose of study treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, are not using steroids for at least 28 days prior to study treatment, and have not received prior cranial irradiation for at least 3 months prior to study treatment.
- Patients with a known additional malignancy that is progressing or requires active treatment. EXCEPTIONS include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
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- No prior external beam radiation therapy to the vagina, pelvis, and/or abdomen will be allowed.
- Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or other serious medical condition or social situations that in the judgement of the Investigator(s) would interfere or limit compliance with study requirements/treatments.
- Receiving systemic steroid therapy or any other form of immunosuppressive therapy within 21 days prior to the first dose of study treatment. Note: Patients with 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) and/or requiring replacement therapy (i.e., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Evidence of interstitial lung disease or active, non-infectious pneumonitis.
- Evidence of uncontrolled hypertension as documented in the patient's medical record.
- Known psychiatric illness/condition or substance abuse disorders that in the judgement of the Investigator(s) would interfere with cooperation with requirements of the study.
- Is pregnant or breastfeeding or expecting to conceive within the projected duration of the study, starting with the pre-screening or screening visit through 120 days after the last dose of study treatment.
- Patients with uncontrolled human immunodeficiency virus (HIV) infection, which is defined as follows:
- Antiviral therapy treatment for <4 weeks AND
- Have an HIV viral load ≥400 copies/mL prior to enrollment.
- Patients with uncontrolled hepatitis B virus (HBV) infection or who are chronic carriers of hepatitis B infection, which is defined as:
- Hepatitis B surface antigen reactive (HbsAg-positive), undetectable or low HBV DNA, and with normal ALT levels who are not on HBV therapy
- Individuals who have serologic evidence of a resolved prior HBV infection (ie, HBSAg-negative and anti-core hepatitis B antibody positive (anti-Hepatitis B core -positive)
- Patients with active, untreated hepatitis C virus (HCV) infection or who have not completed their HCV antiviral regimen. Patients with a history of HCV infection may participate in this study if their HCV ribonucleic acid (RNA) level is below the limit of quantification.
- Received live vaccine within 30 days prior to the first dose of study treatment.
- Patient has active Mycobacterium tuberculosis infection (tuberculosis or TB).
- A QT interval corrected for heart rate using Bazett's formula (QTcB) ≥ 480msec.
- Patient receiving concurrent additional biologic therapy.
- Patients with impaired decision-making capacity.
- Patients who have not recovered from major surgery.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Miami
Miami, Florida, 33136
Aaron H Wolfson, MD, FACR, 954-698-3680, awolfson@med.miami.edu
Aaron H Wolfson, MD, FACR
About this study
Official title: Phase 1 Clinical Trial of Lenvatinib, Pembrolizumab and Hypofractionated Pelvic Radiation Therapy for Mismatch Repair Proficient (pMMR) Recurrent/Unresectable Endometrial Carcinoma
The purpose of this research study is to see if it is feasible to combine a fixed dose of pembrolizumab and a daily dose of oral lenvatinib, along with daily treatments of an abbreviated course of pelvic external beam radiation therapy, to support cancer cells in multiplying and spreading to other body sites.
- Being tested
- Lenvatinib, Pembrolizumab, Hypofractionated External Beam Radiation Therapy, High-Dose Rate (HDR) Brachytherapy
- Medical subject headings
- Endometrial Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LenvatinibDrug
Also called Lenvima
Lenvatinib will be self-administered orally (PO) by participants in a 3+3 escalation/de-escalation design. Participants will receive one of the following four dose levels:
- Dose level 1: 4 mg
- Dose level 2: 8 mg
- Dose level 3: 12 mg (Starting dose)
- Dose level 4: 16 mg
PembrolizumabDrug
Also called Keytruda
Pembrolizumab 200 mg will be administered intravenously (IV) once on Days 1, 22 and 43.
Hypofractionated External Beam Radiation TherapyRadiation
Whole pelvic HypoFx EBRT consisting of 16 fractions of radiation given at a dose of 2.5 Gy per fraction for a total dose of 40.0 Gy.
A pelvic boost HypoFx EBRT consisting of 7 fractions of radiation given at a dose of 2.5 Gy per fraction for a total dose of 17.5 Gy, delivered to site(s) of gross disease of at least 1.0 cm in size.
High-Dose Rate (HDR) BrachytherapyRadiation
Vaginal high-dose rate (HDR) brachytherapy administered per standard of care (SoC) techniques.
| Study group | Role | What they receive |
|---|---|---|
| Lenvatinib, Pembrolizumab and Hypofractionated (HypoFx) External Beam Radiation Therapy (EBRT) Group | Experimental | Participants in this group will receive a combination treatment of Lenvatinib, Pembrolizumab, and HypoFx Pelvic EBRT over a period of approximately 10 to 12 weeks:
* Lenvatinib self-administered daily starting on Day 1 of the study treatment period and continuing until the last dose of whole pelvic HypoFx EBRT is received.
* Pembrolizumab administered on Day 1, 22 and 43.
* Whole pelvic HypoFx EBRT beginning on Day 22.
After receiving whole pelvic Hypo EBRT, participants will receive a boost course of radiation therapy using one of the following techniques:
* Pelvic boost HypoFx EBRT to be administered over a period of 1.5 to 2 weeks; OR
* Vaginal HDR brachytherapy boost to be administered over a period of 2 to 3 weeks, depending on the lesion thickness; OR
* Both pelvic boost HypoFx EBRT pelvic plus vaginal HDR brachytherapy boost.
The overall radiation therapy treatment time for whole pelvic HypoFx RT and radiation boost treatments is approximately 7 weeks. Receives: Drug: Lenvatinib; Drug: Pembrolizumab; Radiation: Hypofractionated External Beam Radiation Therapy; Radiation: High-Dose Rate (HDR) Brachytherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recommended Phase 2 Dose (RP2D) of Lenvatinib
The RP2D will be the highest dose of Lenvatinib that in combination with Pembrolizumab and Hypofractionated (HypoFx) pelvic External Beam Radiotherapy (EBRT) yields less than 2 Dose Limiting Toxicities (DLTs) in 6 patients.
Measured: Up to 12 weeks
Number of Participants Experiencing Treatment-Related Toxicity: Dose-Limiting Toxicities (DLTs)
The number of participants experiencing treatment-related DLTs will be reported. DLTs will be assessed by the treating physician using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.
Measured: Up to 12 weeks
Number of Participants Experiencing Treatment-Related Toxicity: Adverse Events (AEs)
The number of participants experiencing treatment-related adverse events (AEs) will be reported. AEs will be assessed by the treating physician using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.
Measured: Up to 12 weeks
Secondary outcomes (2)
Overall Response Rate (ORR)
ORR is defined as the number of participants achieving a Complete Response (CR) or Partial Response (PR) to study therapy according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
Measured: Up to 12 weeks
Number of Participants Experiencing Non-Treatment-Related Adverse Events
The number of participants experiencing non-treatment-related adverse events (AEs) will reported. AEs will be assessed by the treating physician using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.
Measured: Up to 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2022
- Study start15 Apr 2023
- Primary completion15 Apr 2029 (estimated)
- Study completion15 Apr 2034 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent Endometrial CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Aaron Wolfson
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Aaron Wolfson, University of Miami
- Investigators
- Aaron H Wolfson, MD, FACR, Principal investigator, University of Miami
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05603910
- Sponsor's protocol ID
- 20220813
- Status last verified
- Jul 2026
- First submitted
- 28 Oct 2022
- Last updated
- 3 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No