RECRUITING

Phase 1 Clinical Trial of Lenvatinib, Pembrolizumab and Hypofractionated Pelvic Radiation Therapy for pMMR Recurrent/Unresectable Endometrial Carcinoma

Conditions

Recurrent Endometrial Carcinoma Unresectable Endometrial Carcinoma

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

Phase 1 Clinical Trial of Lenvatinib, Pembrolizumab and Hypofractionated Pelvic Radiation Therapy for Mismatch Repair Proficient (pMMR) Recurrent/Unresectable Endometrial Carcinoma

Quick Facts

Study Start:2023-04-15

Study Completion:2030-04-15

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05603910

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:FEMALE

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Biopsy-proven recurrent pMMR EC following surgery alone or de novo unresectable pMMR EC for whom External beam radiation therapy (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, and serous adenocarcinoma 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 six months (\>6 months), a fresh biopsy must be obtained. 2. 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).13 3. Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (Karnofsky score ≥50). See APPENDIX A. 4. Patients must have pMMR tumor subtype(s). 5. Patients must have normal organ and marrow function as defined below: * 1,500 cells/mm³ Platelets * 100,000 cells/mm³ Hemoglobin * 9.0 g/dL Renal Serum creatinine or Measured or calculated a creatinine clearance glomerular filtration rate (GFR) can also be used in place of creatinine or creatinine clearance (CrCl) * 2.5 mg/dL a CrCl should be calculated per institutional standard. 6. 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. For more information, see Section 4.8. 7. Ability to understand and the willingness to sign a written informed consent document. 8. Women age ≥18 years old.	1. 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. 2. Patients with Mismatch repair deficient (dMMR) and endometrial carcinomas. 3. Patients with dMMR and uterine carcinosarcomas. 4. Patients with known active central nervous system (CNS) metastases and/or carcinomatous meningitis. 5. Patients with a known additional malignancy that is progressing or requires active treatment. 6. Prior treatment with lenvatinib, anti-programmed cell death-1(PD)-1, anti-PD-L1, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways. 7. Patients who are planned to receive vaginal brachytherapy as their pelvic boost course of radiation as determined by their treating physician(s). 8. No prior radiation therapy to the vagina, pelvis, or abdomen will be allowed. 9. 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. 10. Receiving systemic steroid therapy or any other form of immunosuppressive therapy within 21 days prior to the first dose of study treatment. 11. Evidence of interstitial lung disease or active, non-infectious pneumonitis. 12. Evidence of uncontrolled hypertension as documented in the patient's medical record. 13. 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. 14. 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. 15. Patients with uncontrolled human immunodeficiency virus (HIV) infection, which is defined as follows: 1. Antiviral therapy treatment for \<4 weeks AND 2. Have an HIV viral load ≥400 copies/mL prior to enrollment. 16. Patients with uncontrolled hepatitis B virus (HBV) infection or who are chronic carriers of hepatitis B infection, which is defined as: 1. Hepatitis B surface antigen reactive (HbsAg-positive), undetectable or low HBV DNA, and with normal ALT levels who are not on HBV therapy 2. 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) 17. 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. 18. Received live vaccine within 30 days prior to the first dose of study treatment. 19. Patient has active Mycobacterium tuberculosis infection (tuberculosis or TB). 20. A QT interval corrected for heart rate using Bazett's formula (QTcB) ≥ 480msec. 21. Patient receiving concurrent additional biologic therapy. 22. Patients with impaired decision-making capacity. 23. Patients who have not recovered from major surgery.

Inclusion Criteria

Exclusion Criteria

1. Biopsy-proven recurrent pMMR EC following surgery alone or de novo unresectable pMMR EC for whom External beam radiation therapy (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, and serous adenocarcinoma 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 six months (\>6 months), a fresh biopsy must be obtained.
2. 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).13
3. Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (Karnofsky score ≥50). See APPENDIX A.
4. Patients must have pMMR tumor subtype(s).
5. Patients must have normal organ and marrow function as defined below:
* 1,500 cells/mm³ Platelets
* 100,000 cells/mm³ Hemoglobin
* 9.0 g/dL Renal Serum creatinine or Measured or calculated a creatinine clearance glomerular filtration rate (GFR) can also be used in place of creatinine or creatinine clearance (CrCl)
* 2.5 mg/dL a CrCl should be calculated per institutional standard.
6. 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. For more information, see Section 4.8.
7. Ability to understand and the willingness to sign a written informed consent document.
8. Women age ≥18 years old.

1. 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.
2. Patients with Mismatch repair deficient (dMMR) and endometrial carcinomas.
3. Patients with dMMR and uterine carcinosarcomas.
4. Patients with known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
5. Patients with a known additional malignancy that is progressing or requires active treatment.
6. Prior treatment with lenvatinib, anti-programmed cell death-1(PD)-1, anti-PD-L1, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
7. Patients who are planned to receive vaginal brachytherapy as their pelvic boost course of radiation as determined by their treating physician(s).
8. No prior radiation therapy to the vagina, pelvis, or abdomen will be allowed.
9. 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.
10. Receiving systemic steroid therapy or any other form of immunosuppressive therapy within 21 days prior to the first dose of study treatment.
11. Evidence of interstitial lung disease or active, non-infectious pneumonitis.
12. Evidence of uncontrolled hypertension as documented in the patient's medical record.
13. 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.
14. 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.
15. Patients with uncontrolled human immunodeficiency virus (HIV) infection, which is defined as follows:
1. Antiviral therapy treatment for \<4 weeks AND
2. Have an HIV viral load ≥400 copies/mL prior to enrollment.
16. Patients with uncontrolled hepatitis B virus (HBV) infection or who are chronic carriers of hepatitis B infection, which is defined as:
1. Hepatitis B surface antigen reactive (HbsAg-positive), undetectable or low HBV DNA, and with normal ALT levels who are not on HBV therapy
2. 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)
17. 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.
18. Received live vaccine within 30 days prior to the first dose of study treatment.
19. Patient has active Mycobacterium tuberculosis infection (tuberculosis or TB).
20. A QT interval corrected for heart rate using Bazett's formula (QTcB) ≥ 480msec.
21. Patient receiving concurrent additional biologic therapy.
22. Patients with impaired decision-making capacity.
23. Patients who have not recovered from major surgery.

Contacts and Locations

Study Contact

Aaron H Wolfson, MD, FACR

CONTACT

9546983680

awolfson@med.miami.edu

Principal Investigator

Aaron H Wolfson, MD, FACR

PRINCIPAL_INVESTIGATOR

University of Miami

Study Locations (Sites)

University of Miami

Miami, Florida, 33136

United States

Collaborators and Investigators

Sponsor: Aaron Wolfson

Aaron H Wolfson, MD, FACR, PRINCIPAL_INVESTIGATOR, University of Miami

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-04-15

Study Completion Date2030-04-15

Study Record Updates

Study Start Date2023-04-15

Study Completion Date2030-04-15

Terms related to this study

Additional Relevant MeSH Terms

Recurrent Endometrial Carcinoma
Unresectable Endometrial Carcinoma