An Endometrial Cancer Study for Women With Recurrent or Persistent Endometrial Cancer
Condition: Endometrial Cancer
MeSH terms: Endometrial Neoplasms
Intervention: Sodium Cridanimod; progestin therapy
Intervention description: The study will investigate the efficacy of Sodium Cridanimod in conjunction with progestin therapy in a population of subjects with endometrial cancer, who have failed progestin monotherapy or who have been identified as PrR negative.; The study will investigator the use of progestin therapy in conjunction with Sodium Cridanimod
Intervention MeSH terms: Megestrol; Megestrol Acetate; Progestins; 10-carboxymethyl-9-acridanone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: Phase 2, Single Arm, Two Period Study
Masking: None (Open Label)
Enrollment: 25.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Endometrial cancer; Recurrent or persistent endometrial carcinoma; Progesterone Receptor Negative; Sodium Cridanimod

Summary:

      This is an open-label, multi-center, single-arm, two-period Phase 2 study. The study will
      investigate the efficacy of Sodium Cridanimod in conjunction with progestin therapy in a
      population of subjects with recurrent or persistent endometrial cancer, who have failed
      progestin monotherapy or who have been identified as Progesterone Receptor (PrR) negative.
      All patients must have endometrial cancer PrR status determined from an archival sample at
      Screening. The PrR status (positive or negative) will be determined by central laboratory by
      ImmunoHistoChemistry (IHC) testing.

      There are two treatment periods and a follow-up period within the study.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Female patients 18 years of age or older;

          2. Histologically confirmed serous carcinoma or endometrioid type of endometrial
             carcinoma (histological documentation of recurrence is not required);

          3. Recurrent or persistent progressive disease which is refractory to curative therapy or
             established treatments and cannot be treated with surgery or radiotherapy;

          4. Measurable disease, as defined by RECIST 1.1 criteria;

          5. At least one "target lesion" to be used to assess response, as defined by RECIST 1.1
             criteria. Tumors within a previously irradiated field will be designated as
             "non-target" lesions unless previous progression is documented;

          6. Availability of archived tumor tissue sample that can be used for assessment of PrR
             status by the central laboratory;

          7. GOG (Gynecologic Oncology Group) performance status 0-2 (refer to Appendix A);

          8. Calculated Glomerular filtration rate ≥ 50 mL/min;

          9. Total bilirubin ≤ 2.5 times upper limit of normal (ULN);

         10. AST ≤ 2.5 times ULN (≤ 5 times ULN for patients with liver metastases);

         11. Alkaline phosphatase ≤ 2.5 times ULN (≤ 5 times ULN for patients with liver
             metastases);

         12. Albumin ≥ 3.0 mg/dL;

         13. Ability to take oral medication;

         14. Patients able to understand the nature of the study and who are willing to give
             written informed consent;

         15. And for Treatment Period 2 only: 1) Patients participating in Treatment Period 1 must
             have had disease progression after receiving at least 4 weeks of progestin therapy or
             2) Patients must be determined as PrR negative status at Screening.

        Exclusion Criteria:

          1. Mixed histology of the tumor or evidence of tumor histology other than serous
             carcinoma or endometrioid type of endometrial carcinoma;

          2. Concurrent systemic corticosteroid therapy;

          3. Concurrent oral contraceptive use / Women of childbearing potential not using highly
             effective means of contraception;

          4. Pregnancy confirmed by pregnancy test / Lactating women;

          5. Prior therapy with hormonal progestin agents;

          6. Patients who are candidates for treatment with standard chemotherapy agents (there is
             no limit to the number of lines of chemotherapy);

          7. History of blood clot;

          8. History of known bleeding disorder (i.e. disseminated intravascular coagulation or
             clotting factor deficiency);

          9. Major surgery within 4 weeks prior to the start of the study;

         10. Patients with clinically significant illnesses which, according to the Investigator,
             could compromise participation in the study;

         11. History of other clinically active malignancies within 5 years, except for carcinoma
             in situ of the cervix, basal cell carcinoma, or squamous carcinoma of the skin.

         12. Known hypersensitivity or idiosyncratic reaction to any of the study drugs (Sodium
             Cridanimod, megestrol acetate, lidocaine) and excipients;

         13. Patients with known brain metastases;

         14. Patients currently receiving any other investigational agents;

         15. Patients currently receiving any other anticancer therapies;

         16. Participation in any other clinical study within the last 4 weeks prior to the start
             of the study