Clinical Trials /

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

NCT03955978

Description:

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.

Related Conditions:
  • Endometrial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: TSR-042 in Addition to Standard of Care Definitive Radiation for Inoperable Endometrial Cancer
  • Official Title: A Phase I Study of PD-1 Inhibition With TSR-042 in Addition to Standard of Care Definitive Radiation for Inoperable Endometrial Cancer

Clinical Trial IDs

  • ORG STUDY ID: 19-x012
  • NCT ID: NCT03955978

Conditions

  • Endometrial Cancer
  • Cancer of the Endometrium

Interventions

DrugSynonymsArms
TSR-042TSR-042 and Brachytherapy

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
TSR-042 and BrachytherapyExperimentalPatients will receive four doses of TSR-042. The first dose is given 21 days prior to the first brachytherapy fraction. The second dose is given at the time of fraction #1. The third dose is given at the time of fraction #4. The final dose is given 1 week after fraction #6. Brachytherapy will consist of 6 weekly fractions of 6 Gy per fraction (total 36Gy)
  • TSR-042

Eligibility Criteria

        Inclusion Criteria:

          -  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.

          -  Participant must agree to not donate blood during the study or for 90 days after the
             last dose of study treatment.

          -  Female participant has a negative serum pregnancy test the day of and prior to taking
             study treatment if of childbearing potential and agrees to abstain from activities
             that could result in pregnancy from screening through 180 days after the last dose of
             study treatment, or is of non-childbearing potential. Non-childbearing potential is
             defined as follows (by other than medical reasons):

             *≥45 years of age and has not had menses for >1 year

               -  Patients who have been amenorrhoeic for <2 years without history of a
                  hysterectomy and oophorectomy must have a follicle stimulating hormone value in
                  the postmenopausal range upon screening evaluation.

               -  Post-bilateral oophorectomy, or post-tubal ligation. Documented oophorectomy must
                  be confirmed with medical records of the actual procedure or confirmed by an
                  ultrasound. Tubal ligation must be confirmed with medical records of the actual
                  procedure, otherwise the patient must be willing to use 2 adequate barrier
                  methods throughout the study, starting with the screening visit through 180 days
                  after the last dose of study treatment. See Section 4.4 for a list of acceptable
                  birth control methods. Information must be captured appropriately within the
                  site's source documents.

               -  Note: Abstinence is acceptable if this is the established and preferred
                  contraception for the patient.

          -  Participant must agree to not breastfeed during the study or for 180 days after the
             last dose of study treatment.

          -  Ability to understand and willingness to sign an IRB approved written informed consent
             document (or that of legally authorized representative, if applicable).

        Exclusion Criteria:

          -  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).

          -  Participant has known active hepatitis B (eg, hepatitis B surface antigen [HBsAg]
             reactive) or hepatitis C (eg, hepatitis C virus [HCV] ribonucleic acid [qualitative]
             is detected).

          -  Participant has an active autoimmune disease that has required systemic treatment in
             the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or
             immunomodulatory drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic
             corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is
             not considered a form of systemic treatment.

          -  Participant must not have a history of interstitial lung disease.

          -  Participant has received a live vaccine within 14 days of initiating protocol therapy.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety and tolerability of the regimen as measured by the grade of toxicities experienced as assessed by CTCAE v5.0
Time Frame:6 weeks
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Progression-free survival (PFS)
Time Frame:2 years
Safety Issue:
Description:PFS is defined as the time from last TSR-042 administration to disease progression or death. Response and progression will be evaluated in this study in a qualitative fashion by symptoms (such as bleeding, abdominal or pelvic pain, changes of bowel or bladder habits lasting more than two weeks), clinical exam and/or evidence of disease on imaging by RECIST 1.1 as not all patients will have measurable disease at baseline on imaging. Persistent/recurrent clinical disease will be confirmed by biopsy whenever possible.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Washington University School of Medicine

Trial Keywords

  • Immune checkpoint inhibition
  • Radiation-induced immune response
  • CyTOF

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