Brief Title
Radiation and TSR-042 in People With Endometrial Cancer After They Receive Surgery
Official Title
Adjuvant Checkpoint Blockade Plus Radiation In Locally Advanced, Mismatch Repair Deficient/Microsatellite Instability-High (MMR-D/MSI-H) Endometrial Cancer
Brief Summary
This study will test whether the combination of radiation and TSR-042 is an effective
treatment for women with MMR-D/MSI-H endometrial cancer who have recently undergone surgery.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Incidence of dose limiting toxicities (DLTs) (Safety Run-in only)
Condition
Endometrial Cancer
Intervention
Intensity modulated radiation therapy (IMRT)
Study Arms / Comparison Groups
Radiation and TSR-042
Description: Patients will undergo standard intensity modulated radiation therapy (IMRT) to the pelvic nodes and vaginal cuff (total dose of 45-50.4Gy at 1.8 Gy per fraction) for 5-6 weeks82 and receive IV TSR-042 every 3 weeks for 4 cycles followed by 1 dose of 1000mg (C5). Patients will receive a maximum of 5 cycles of TSR-042.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Radiation
Estimated Enrollment
31
Start Date
April 2, 2021
Completion Date
February 2023
Primary Completion Date
February 2023
Eligibility Criteria
Inclusion Criteria:
- Age 18 years or older
- ECOG performance status 0-1
- Endometrial cancer: all histologies
- MMR-D or MSI-H by IHC, PCR or NGS testing. For patients with outside testing, archival
tissue will be required for NGS testing at MSKCC
- Patients with hypermethylation of MMR gene promoters (MLH1, MSH2, MSH6 or PMS2)
will be included
- POLE-mutated endometrial cancers will be included
- Must have undergone a complete surgical staging and have stage III/IVA disease.
- Patients with residual disease after surgery can still be enrolled.
- PatienSurgery completed between 3 weeks and 12 weeks (inclusive) before cycle 1
day 1 of therapy, and must have adequately recovered from surgery and any
complications of surgery.ts with isolated tumor cells in lymph nodes found on
surgery will be counted as clinical stage III disease
- Surgery completed between 3 weeks and 12 weeks (inclusive) before cycle 1 day 1 of
therapy, and must have adequately recovered from surgery and any complications of
surgery.
- Has a negative serum pregnancy test within 7 days prior to taking study treatment if
of childbearing potential, and agrees use an adequate method of contraception from
screening through 150 days after the last dose of study treatment, or is of
nonchildbearing potential. Nonchildbearing 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-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation.
Documented hysterectomy or 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 an adequate birth control method throughout the study,
starting with the screening visit through 150 days after the last dose of study
treatment. See 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 150 days after the
last dose of study treatment.
- Demonstrate adequate organ function as defined below. All screening labs should be
performed within 14 days of treatment initiation.
- Absolute neutrophil count (ANC) ≥1,500 /mcL
- Platelets ≥100,000 / mcL
- Hemoglobin ≥9 g/dL
- Serum creatinine GFR ≥ 45
- Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with
total bilirubin levels > 1.5 ULN. Except patients with Gilbert's disease (≤3x
ULN)
- AST and ALT ≤2.5 ULN OR ≤ 5 X ULN for subjects with liver metastases
- Albumin >3 mg/dL
- 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 partial thromboplastin (PTT) is
within therapeutic range of intended use of anticoagulants
Exclusion Criteria:
- Has had prior chemotherapy, targeted therapy, or investigational therapy for endometrial
cancer.
- Patients who have received prior chemotherapy, targeted therapy, or other
investigational therapies for other cancers and are in remission/cured may be included
at the discretion of the treating investigator in consultation with the study PI.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 agent
for endometrial cancer.
- Unfit for Radiation Therapy due to the following:
- 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.
- Patients with a prior history of pelvic radiation
- Patients with a prior known history or current diagnosis of a vesicovaginal,
enterovaginal, or colovaginal fistula.
- Any hematological abnormality or disorder that would be a contraindication to
radiation per the treating physician.
- Hypersensitivity to TSR-042 or any of its excipients
- Patients with diagnosis of immunodeficiency or patients receiving systemic
steroid therapy or any other form of immunosuppressive therapy within 7 days
prior to the first dose of trial treatment.
- Patients who have received acute, low dose, systemic immunosuppressant
medications (e.g., dexamethasone containing antiemetic regimen or steroids as CT
scan contrast premedication) may be enrolled.
- The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for
patients with orthostatic hypotension or adrenocortical insufficiency is allowed.
- Total systemic steroid dose cannot exceed an equivalent of 10mg of prednisone daily
and dose must be stable for at least 4 weeks prior to initiating protocol therapy
- Has a history of active TB (Bacillus tuberculosis)
- Has evidence of active, non-infectious pneumonitis.
- Has history of interstitial lung disease
- Has an active infection requiring systemic therapy with intravenous antibiotics
- Has a history or current evidence of any condition, therapy, or laboratory
abnormality that might confound the results of the trial, interfere with the
subject's participation for the full duration of the trial, or is not in the best
interest of the subject to participate, in the opinion of the treating (within 90
days) myocardial infarction, chronic obstructive pulmonary disease, uncontrolled
major seizure disorder, unstable spinal cord compression, and superior vena cava
syndrome.
- Has psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
- Prior malignancy within the past 2 years prior to start of treatment, with the
exception of early stage cancers with low likelihood of recurrence in the opinion
of treating investigator.
- Patients with prior allogeneic bone marrow transplantation or prior solid organ
transplantation.
- Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease; systemic lupus erythematosus; Wegener syndrome
[granulomatosis with polyangiitis]; myasthenia gravis; Graves' disease;
rheumatoid arthritis, hypophysitis, uveitis) within the past 3 years prior to the
start of treatment or patients requiring immunosuppressive therapy for the
autoimmune disease. The following are exceptions to this criterion:
- Subjects with vitiligo or alopecia
- Subjects with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone
replacement or psoriasis not requiring systemic treatment.
- Has a history of uncontrolled Human Immunodeficiency Virus (HIV) (HIV 1/2
antibodies).
- Patients with well-controlled HIV on therapy with undetectable viral loads and
absolute CD4 count above 300 may be included.
- Has active Hepatitis B (e.g., HBsAg reactive/HBV DNA PCR positive) or Hepatitis C
(e.g., HCV RNA [qualitative] is detected).
- Patients with a positive Hep B cAb will require prophylactic therapy prior to
enrollment.
- Has received a live vaccine within 30 days of planned start of study therapy.
- Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines
and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live
attenuated vaccines, and are not allowed.
- Is unwilling to give written informed consent, unwillingness to participate, or
inability to comply with the protocol for the duration of the study. The use of
LAR for cognitively impaired patients is not permitted.
Gender
Female
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Ying Liu, MD, MPH, 646-888-4946, [email protected]
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT04774419
Organization ID
20-491
Responsible Party
Sponsor
Study Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Tesaro, Inc.
Study Sponsor
Ying Liu, MD, MPH, Principal Investigator, Memorial Sloan Kettering Cancer Center
Verification Date
April 2021