TSR-042 in Addition to Standard of Care Definitive Radiation for Inoperable Endometrial Cancer

NCT03955978 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 201907060
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with inoperable endometrial cancer have limited treatment options. PD-L1 expression is common in endometrial cancers and RT induces tumor and systemic changes that induce the immune system. The purpose of this trial is to evaluate anti-PD-1/PD-L1 axis therapy in conjunction of standard of care RT for patients with inoperable endometrial cancer in order to establish the safety and efficacy of inducing an anti-tumor immune response.

Conditions

Endometrial Cancer; Cancer of the Endometrium

Keywords

Immune checkpoint inhibition; Radiation-induced immune response; CyTOF

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of the regimen as measured by the grade of toxicities experienced as assessed by CTCAE v5.0

  Through 30 days after completion of treatment (estimated to be 10 weeks)

Secondary Outcomes (1)

• Progression-free survival (PFS)

  2 years

Study Arms (1)

TSR-042 and Brachytherapy

EXPERIMENTAL

* Patients will receive four doses of TSR-042. The first dose is given 21 days prior to the first planned brachytherapy fraction. The second dose is given 21 (+3) days later, corresponding to the time of brachytherapy fraction #1. The third dose is given 21 (+3) days after dose 2, corresponding to the time of brachytherapy fraction #4. The fourth dose is given 21 (+3) days after dose corresponding to 1 weeks after brachytherapy fraction #6. * Brachytherapy will consist of 6 weekly fractions of 6 Gy per fraction (total 36Gy)

Drug: TSR-042; Radiation: Brachytherapy; Procedure: Endometrial biopsy; Procedure: Blood draw for immune response

Interventions

TSR-042 DRUG

-TSR-042 is administered intravenously via a 30-minute (-5-minute/+15-minute infusion window allowed) infusion

TSR-042 and Brachytherapy

Brachytherapy RADIATION

-This trial will include image-guided brachytherapy with three-dimensional (3-D) treatment planning and in cases where pelvic radiation is deemed appropriate by the treating radiation oncologist, external beam radiation therapy (EBRT) using intensity modulated radiation therapy (IMRT) technique.

TSR-042 and Brachytherapy

Endometrial biopsy PROCEDURE

-Prior to the start of treatment with TSR-042. If this biopsy yields insufficient tumor tissue, an archival sample may be requested, with Fraction 1 of brachytherapy, with Fraction 4 of brachytherapy

TSR-042 and Brachytherapy

Blood draw for immune response PROCEDURE

-Prior to the start of any treatment, at the time of brachytherapy fractions 1 and 4 (corresponding to endometrial biopsy), prior to fourth dose of TSR-042, 6 weeks after the completion of all protocol related therapy

TSR-042 and Brachytherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Newly diagnosed biopsy proven The International Federation of Gynecology and Obstetrics (FIGO) clinical stage I or II endometrial carcinoma.
• Histology of FIGO grade 1-3 endometrioid endometrial carcinoma.
• Medically inoperable per treating gynecologic oncologist.
• Candidate for definitive radiation therapy as determined by treating radiation oncologist.
• At least 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Participant must have adequate organ function, defined as follows:
• Absolute neutrophil count ≥ 1,500/µL
• Platelets ≥ 100,000/µL
• Hemoglobin ≥ 9 g/dL; transfusion is allowed to meet this criterion
• Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine clearance 60mL/min using the Cockcroft-Gault equation
• Total bilirubin ≤ 1.5 x ULN (≤2.0 in patients with known Gilberts syndrome) OR direct bilirubin ≤ 1 x ULN
• Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x ULN unless liver metastases are present, in which case they must be ≤ 5 x ULN
• International normalized ratio (INR) or prothrombin time (PT) ≤1.5× ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin (PTT) is within therapeutic range of intended use of anticoagulants. Activated partial thromboplastin time (aPTT) ≤1.5× ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• Participant receiving corticosteroids may continue as long as their dose is stable for at least 4 weeks prior to initiating protocol therapy.

You may not qualify if:

• Any prior treatment for endometrial cancer or currently receiving chemotherapy for endometrial cancer.
• Evidence of metastatic disease outside of the cervix or uterus as determined on CT or MRI.
• A history of other malignancy ≤ 3 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only.
• Previous treatment with an anti-PD-1, anti-PD-L1, or any PD-L2 drug.
• Known brain or leptomeningeal metastases. Patients with known brain metastases must be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to TSR-042 or other agents used in the study.
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 7 days of study entry.
• Participant must not be simultaneously enrolled in any interventional clinical trial
• Participant must not have had major surgery ≤ 3 weeks prior to initiating protocol therapy and participant must have recovered from any surgical effects.
• Participant must not have received investigational therapy ≤ 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is shorter, prior initiating protocol therapy.
• Participant has had radiation therapy encompassing \>20% of the bone marrow within 2 weeks; or any radiation therapy within 1 week prior to Day 1 of protocol therapy.
• Participant must not have a serious, uncontrolled medical disorder, nonmalignant systemic disease, or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 90 days) myocardial infarction, chronic obstructive pulmonary disease, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent.
• Patient experienced ≥ Grade 3 immune-related AE with prior immunotherapy, with the exception of non-clinically significant lab abnormalities.
• Participant has a diagnosis of immunodeficiency or has receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to initiating protocol therapy.
• Participant has a known history of human immunodeficiency virus (type 1 or 2 antibodies).

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Tesaro, Inc.: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (3)

• Acharya S, Esthappan J, Badiyan S, DeWees TA, Tanderup K, Schwarz JK, Grigsby PW. Medically inoperable endometrial cancer in patients with a high body mass index (BMI): Patterns of failure after 3-D image-based high dose rate (HDR) brachytherapy. Radiother Oncol. 2016 Jan;118(1):167-72. doi: 10.1016/j.radonc.2015.12.019. Epub 2015 Dec 29.

  PMID: 26743834 BACKGROUND

• Sharabi AB, Lim M, DeWeese TL, Drake CG. Radiation and checkpoint blockade immunotherapy: radiosensitisation and potential mechanisms of synergy. Lancet Oncol. 2015 Oct;16(13):e498-509. doi: 10.1016/S1470-2045(15)00007-8.

  PMID: 26433823 BACKGROUND

• Spiotto M, Fu YX, Weichselbaum RR. The intersection of radiotherapy and immunotherapy: mechanisms and clinical implications. Sci Immunol. 2016 Sep;1(3):EAAG1266. doi: 10.1126/sciimmunol.aag1266. Epub 2016 Sep 30.

  PMID: 28018989 BACKGROUND

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

dostarlimab; Brachytherapy; Blood Specimen Collection; Immunity

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Immune System Phenomena

Study Officials

• Stephanie Markovina, M.D, Ph.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2019
• First Posted: May 20, 2019
• Study Start: October 15, 2019
• Primary Completion: March 22, 2024
• Study Completion (Estimated): February 1, 2029
• Last Updated: January 6, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)