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Study of Lenvatinib w/ Pembro in Black Participants w/Mismatch Repair-Prof Recurrent Endometrial Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT05263492
Recruitment Status : Recruiting
First Posted : March 2, 2022
Last Update Posted : April 13, 2022
Information provided by (Responsible Party):
Virginia Commonwealth University

Brief Summary:
Determine the efficacy of the combination of lenvatinib and pembrolizumab in Black participants compared to the efficacy reported in the historical trials leading to US FDA approval of the regimen

Condition or disease Intervention/treatment Phase
Endometrial Cancer Mismatch Repair-Proficient Recurrent Endometrial Cancer Drug: Lenvatinib Drug: Pembrolizumab Phase 2

Detailed Description:
This study is a single-arm, open-label, multicenter phase 2 trial designed to prospectively evaluate the safety and efficacy of lenvatinib in combination with pembrolizumab for mismatch repair proficient recurrent endometrial cancer in Black patients (a population under-represented on 2 FDA registration trials).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter, Open-Label Phase 2 Study to Evaluate the Safety and Efficacy of Lenvatinib in Combination With Pembrolizumab in Black Participants With Mismatch Repair-Proficient Recurrent Endometrial Cancer
Actual Study Start Date : April 1, 2022
Estimated Primary Completion Date : September 30, 2025
Estimated Study Completion Date : September 30, 2035

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Pembrolizumab & Lenvatinib
Lenvatinib, 20 mg administered orally (PO) once daily (QD) during each 21-day cycle, and Pembrolizumab, 200 mg administered by intravenous (IV) infusion on day 1 of each 21-day cycle.
Drug: Lenvatinib
Lenvatinib once a day by mouth every day

Drug: Pembrolizumab
Pembrolizumab through a needle or tube in a vein (intravenously, IV) every 3 weeks.

Primary Outcome Measures :
  1. Determine the objective response rate (ORR) at 24 weeks in Black patients with recurrent endometrial cancer treated with lenvatinib 20 mg orally daily in combination with pembrolizumab 200 mg IV every 3 weeks [ Time Frame: 24 Weeks ]
    Number of patients evaluable for measurement of tumor response evaluated and recorded according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1)

Secondary Outcome Measures :
  1. Determine the median progression free survival (PFS) [ Time Frame: Up to 90 days following the last dose of study treatment ]
    Number of patients who are alive and following last dose of study treatment

  2. Determine the median progression free survival (PFS) [ Time Frame: Up to 90 days following the last dose of study treatment ]
    Number of patients who have not had disease progression following last dose of study treatment

  3. Determine the median progression free survival (PFS) [ Time Frame: Up to 90 days following the last dose of study treatment ]
    Number of patients who have not relapsed following last dose of study treatment

  4. Determine the number of patients with treatment-related adverse events (AEs) in the study population [ Time Frame: Up to 30 days following the last dose of study treatment ]
    Using criteria in the National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0), all AEs captured

  5. Determine the number of patients who discontinue treatment due to treatment-related adverse events (AEs) [ Time Frame: up to 30 days (plus or minus 15 days) following last dose of study treatment ]
    Number of patients who discontinue treatment due to treatment-related AEs.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically and/or cytologically confirmed endometrioid, serous, clear cell, or de-differentiated or undifferentiated endometrial cancer with radiographic and/or clinical evidence of disease progression
  • Documented microsatellite stable disease as tested by either MSI PCR or DNA mismatch repair (MMR) by IHC
  • Self-identify as being of predominantly (>50%) Black race, inclusive of Black, African-American, Black Hispanic (Afro-Latinx), African, or Afro-Caribbean ancestry
  • Received, ineligible for (by investigator determination), or declined platinum containing chemotherapy
  • Received no greater than two prior lines of therapy. Maintenance therapies and hormonal therapies will NOT count as a line of therapy.
  • Measurable disease as determined by RECIST v1.1:
  • At least one lesion of ≥10 mm in the longest diameter for a non-lymph node, or ≥15 mm in the short-axis diameter for a lymph node that is serially measurable using computerized tomography/magnetic resonance imaging (CT/MRI)
  • Target lesions limited to a radiated field must show evidence of substantial size increase according to previous scans to be deemed a target lesion
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
  • Ability to swallow oral medications
  • Patients who are not postmenopausal or have not undergone hysterectomy must have a documented negative serum pregnancy test within 72 hours prior to initiating study treatment

Note: Postmenopausal is defined as any of the following:

  • Age ≥ 60 years
  • Age < 60 years and amenorrheic for at least 1 year with follicle-stimulating hormone (FSH) and plasma estradiol levels in the postmenopausal range
  • Bilateral oophorectomy
  • Patients of child-bearing potential must agree to use a medically accepted method for preventing pregnancy during and for a minimum of 4 months following the last dose of lenvatinib or pembrolizumab
  • Patients with known brain metastases will be eligible if they have completed primary brain therapy (such as whole brain radiotherapy, stereotactic radiosurgery, or complete surgical resection) and if they have remained clinically stable, asymptomatic, and off of steroids for at least 28 days before starting study treatment
  • Toxicities from previous cancer therapies resolved to grade ≤1 unless specified otherwise (exceptions: chronic residual toxicities that in the opinion of the investigator are not clinically relevant, given the known safety/toxicity profiles of Lenvatinib and pembrolizumab, such as alopecia, grade ≤2 anemia; neuropathy related to previous chemotherapy must be resolved to grade ≤2)
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Carcinosarcoma (malignant mixed mullerian tumor), endometrial leiomyosarcoma, or endometrial stromal sarcoma
  • Unstable central nervous system (CNS) metastases
  • Gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib
  • Pre-existing grade ≥3 gastrointestinal or non-gastrointestinal fistula
  • Radiographic evidence of major blood vessel invasion/infiltration
  • Clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study treatment
  • History of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction, cerebrovascular accident, stroke, or cardiac arrhythmia associated with hemodynamic instability within 12 months of the first dose of study treatment
  • Known history or evidence of interstitial lung disease or active, non-infectious pneumonitis
  • Administration of or condition requiring administration of systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to initiating study treatment Exception: Patients with conditions that can be managed with steroids equivalent to or less than an oral prednisone dose of 10 mg daily are not excluded from the study
  • Active autoimmune disease (with the exception of psoriasis) that has required systemic treatment in the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs) or a documented history of clinically severe autoimmune disease or a syndrome that requires systemic steroids or immunosuppressive agents Note: Patients with the conditions or medical history listed below are not excluded from the study.

    • Vitiligo
    • Resolved childhood asthma/atopy
    • Requirement for intermittent use of bronchodilators or local steroid injections or topical steroids
    • Hypothyroidism stable on hormone replacement
    • Sjogren's Syndrome
  • Has received >1 prior systemic chemotherapy regimen (other than adjuvant or neoadjuvant) for endometrial cancer; participants may receive up to two regimens of platinum-based chemotherapy in total, as long as one is given in the neoadjuvant or adjuvant treatment setting
  • Prior anticancer treatment within 28 days of study start
  • Prior treatment with any treatment targeting VEGF-directed angiogenesis, any anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
  • Has received prior treatment with an agent directed to a stimulatory or co-inhibitory T-cell receptor other than an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, and who has discontinued from that treatment due to a grade 3 or higher immune-related adverse event (irAE)
  • Has received prior radiation therapy within 21 days of study start with the exception of palliative radiotherapy to bone lesions, which is allowed if completed 2 weeks of study start; participants must have recovered from all radiation-related toxicities and/or complications prior to randomization
  • Participants with urine protein ≥3.5 gram (g)/24 hour
  • Prolongation of corrected QT (QTc) interval to >480 milliseconds (ms)
  • Left ventricular ejection fraction (LVEF) below the institutional normal range as determined by multigated acquisition scan (MUGA) or echocardiogram (ECHO)
  • Prior immunotherapy (single or dual immune checkpoint inhibition, cellular or vaccine therapy)
  • Administration of a live vaccine within 30 days prior to initiating study treatment Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are permitted; however, intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed. COVID-19 vaccines are allowed and encouraged
  • Administration of any investigational agent within 4 weeks prior to initiating study treatment
  • History of solid organ or allogeneic stem cell transplant
  • Known intolerance to either of the study drugs (or any of the excipients)
  • Known immunodeficiency, eg, human immunodeficiency virus (HIV) Note: HIV testing is not required for eligibility screening
  • Known active hepatitis B or C Note: hepatitis B and C testing is not required for eligibility screening
  • Serious (ie, grade ≥3) uncontrolled infection
  • Pregnancy or breastfeeding
  • Diagnosis or treatment for another malignancy within 2 years prior to study registration, with the following exceptions: complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, any in situ malignancy, and low-risk prostate cancer after curative therapy
  • Medical, psychological, or social condition that, in the opinion of the investigator, may increase the patient's risk or limit the patient's adherence with study requirements

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT05263492

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Contact: Massey Gyn Onc Team 804-628-2582
Contact: Massey CTO Operations Managers

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United States, Virginia
Virginia Commonwealth University Recruiting
Richmond, Virginia, United States, 23298
Contact: Massey Gyn Onc Team    804-628-2582   
Contact: Massey CTO Operations Managers   
Principal Investigator: Leslie Randall, MD         
Sponsors and Collaborators
Virginia Commonwealth University
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Principal Investigator: Leslie Randall, MD Massey Cancer Center
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Responsible Party: Virginia Commonwealth University Identifier: NCT05263492    
Other Study ID Numbers: MCC-21-18659
HM20023447 ( Other Identifier: Virginia Commonwealth University )
First Posted: March 2, 2022    Key Record Dates
Last Update Posted: April 13, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: There are no plans to share individual participant data to other researchers at this time.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Virginia Commonwealth University:
Endometrial Cancer
Mismatch Repair-Proficient
Black Participants
Additional relevant MeSH terms:
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Endometrial Neoplasms
Disease Attributes
Pathologic Processes
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action