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 except for carcinosarcoma (submission of pathology
report is required for all patients who underwent surgery outside of MSK)
- MMR-D or MSI-H (submission of report[s] required for. patients who underwent testing
outside of MSK
- Patients with hypermethylation of MMR gene promoters (MLH1, MSH2, MSH6 or PMS2)
will be included (submission of report is required for patients who underwent
testing outside of MSK)
- 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 with the
exception of peritoneal implants. Those with residual disease after surgery
should be reviewed and approved by the study PI.
- 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
- Creatinine Clearance GFR ≥ 45
- Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with
total bilirubin levels > 1.5 X ULN. Except patients with Gilbert's disease (≤3x
ULN)
- AST and ALT 3 ULN OR ≤ 5 X ULN for subjects with liver metastases
- Albumin >3 mg/dL
- TSH within normal limits. If TSH is not within normal range despite no symptoms
of thyroid dysfunction, normal free T4 level is required.
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 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.
- Patients with a prior or concurrent malignancy whose natural history or treatment does
not have the potential to interfere with the safety or efficacy assessment of the
investigational regimen are eligible for this trial.
- 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
- Subjects with psoriasis not requiring systemic treatment.
- Subjects with history of immune-related hyperthyroidism with total thyroidectomy
currently in remission
- Select situations after approval of study PI
- HIV-infected patients on effective anti-retroviral therapy with undetectable viral
load within 6 months are eligible for this trial
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral
load must be undetectable on suppressive therapy, if indicated.
- Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. For patients with HCV infection who are currently on treatment, they are
eligible if they have an undetectable HCV viral load
- 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
September 2021