An Endometrial Cancer Study for Women With Recurrent or Persistent Endometrial Cancer

A Phase 2, Single Arm, Two Period Study of Sodium Cridanimod in Conjunction With Progestin Therapy in Patients With Endometrial Carcinoma

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.

Study Overview

• Status: Terminated
• Conditions: Endometrial Cancer
• Intervention / Treatment: Drug: Sodium Cridanimod; Drug: progestin therapy

Detailed Description

Treatment Period 1 (Progestin Monotherapy): During Treatment Period 1, all subjects determined to be PrR positive will receive progestin monotherapy, megestrol acetate, for up to 24 weeks. Subjects will have an MRI or CT scan after 12 and 24 weeks of progestin monotherapy, with response to treatment being assessed according to RECIST 1.1 criteria. All subjects that achieve disease control confirmed by tumor assessment after Treatment Period 1, will be ineligible to enter Treatment Period 2. These subjects will be terminated from the trial and treated according to local standards of practice, which may include continued progestin therapy.

Subjects determined to be PrR negative at Screening will not enroll into Treatment Period 1. These subjects will enroll directly into Treatment Period 2.

Treatment Period 2 (Combination Treatment): All subjects determined to be PrR negative at Screening and those who received at least 4 weeks of progestin monotherapy and who experienced disease progression at the conclusion of Treatment Period 1 will enter Treatment Period 2 of the study. During Treatment Period 2, subjects will receive Sodium Cridanimod in combination with continued progestin treatment, megestrol acetate. Subjects will receive treatment until disease progression as defined according to RECIST 1.1 criteria, with response assessments performed at 12-week intervals.

Follow-up Period: Once subjects progress during Treatment Period 2, they will return for a Safety Follow-up Visit 4 weeks following the last treatment, and then continue to be followed for an additional 12-month period for overall survival.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Burbank, California, United States, 91505
      • Providence St. Joseph Medical Center - Gynecology
    • Irvine, California, United States, 92697
      • University of California - Irvine Healthcare
    • Los Angeles, California, United States, 90024
      • UCLA
    • Santa Rosa, California, United States, 95403
      • St. Josephs Heritage Healthcare
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado School of Medicine, Division of Gynecologic Oncology
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Baptist MD Anderson Cancer Center
    • Orlando, Florida, United States, 32804
      • Florida Hospital Cancer Institute
    • Sarasota, Florida, United States, 34239
      • Sarasota Memorial Health Care System
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital [University Gynecologic Oncology]
    • Savannah, Georgia, United States, 31404
      • MUMC - Curtis and Elizabeth Anderson Cancer Institute
  • Idaho
    • Boise, Idaho, United States, 83706
      • Saint Alphonsus Regional Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Kentucky
    • Lexington, Kentucky, United States, 40508
      • University of Kentucky, Markey Cancer Center
  • Louisiana
    • Covington, Louisiana, United States, 70433
      • Women's Cancer Care [Mary Bird Cancer Center at Tammany Parish Hospital]
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • St. Dominic-Jackson Memorial Hospital
  • New York
    • Brooklyn, New York, United States, 11203
      • SUNY Downstate Medical Center
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27517
      • Wake Forest Baptist Health
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Cancer Institute-UC Health Barrett Center
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74146
      • Oklahoma Cancer Specialists and Research Institute, LLC
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Magee Women's Hospital (UPMC)
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Rapid City Regional Cancer Care
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern
    • Galveston, Texas, United States, 77555
      • UT Galveston; University of Texas Medical Branch (UTMB)
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance / University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Sodium Cridanimod & progestin therapy; Sodium Cridanimod and progestin therapy (megestrol acetate) combination

Drug: Sodium Cridanimod; 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.; Drug: progestin therapy; The study will investigator the use of progestin therapy in conjunction with Sodium Cridanimod; Other Names: megestrol acetate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Disease Control (ODC) as Determined by Radiographic Imaging Measurements	Subjects in the Full Analysis Set (FAS) population will be assessed for ODC. The FAS population includes those subjects all treated in TP2 who either undergo a CT or MRI scan with tumor assessment at 12 weeks (i.e. they have not discontinued treatment prior to 12 weeks) or those who have discontinued TP2 prior to 12 weeks solely due to documented disease progression. Radiographic disease progression and responses will be defined using RECIST 1.1 criteria: Control Response(CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions. The appearance of new lesions is also considered progression. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD	During TP2 Every 12 weeks, until disease progression up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	The best overall response was the best response recorded from the start of Treatment Period 2 until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started).To be assigned a status of CR or PR, tumor measurements were confirmed by repeat assessment performed at least four weeks after the criteria for response are first met. Best Overall Response (OR) was determined based on the following combinations of repeat assessments: CR + CR = CR, CR + PR= SD, PD or PR, CR + SD =SD, CR+ PD = SD, CR + NEW= SD, PR + CR= PR, PR + PR= PR, PR+ SD= SD, PR + PD= SD, PR+ NEW = SD.	24 months
Progression-free Survival (PFS)	Progressive Disease was assessed using RECIST Guideline (version 1.1) whereas at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. Progression-free Survival (PFS) was defined as the duration of time from initiation of Treatment Period 2 (Day 0) until disease progression or death from any cause, whichever occurs first. For the purpose of analysis of PFS, subjects with an unknown response were censored.	24 months
Duration of Stable Disease	Stable Disease (SD) was assessed using RECIST Guideline (version 1.1) whereas neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Duration of Stable Disease was defined as the duration of time from initiation of Treatment Period 2 (Day 0) until the criteria for disease progression were first met. For the purpose of analysis of Duration of SD, subjects who died before documented progressive disease were censored.	24 months
Overall Survival (OS)	Once disease progression was documented in Treatment Period 2, subjects returned for the Safety Follow-up Visit four (4) weeks following the last treatment and continued to be followed for an additional 12-month period for overall survival. Overall Survival (OS) was defined as the duration of time from initiation of Treatment Period 2 (Day 0) until the subject's death from any cause. For the purpose of analysis of OS, if a subject is alive at the date of last contact the subject was censored at that date of contact.	12 months

Collaborators and Investigators

• Sponsor: Xenetic Biosciences, Inc.
• Investigators: Study Director: Curtis Lockshin, PhD, Xenetic Biosciences, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 14, 2017
• Primary Completion (ACTUAL): July 17, 2020
• Study Completion (ACTUAL): July 17, 2020

Study Registration Dates

• First Submitted: February 27, 2017
• First Submitted That Met QC Criteria: March 7, 2017
• First Posted (ACTUAL): March 13, 2017

Study Record Updates

• Last Update Posted (ACTUAL): June 7, 2022
• Last Update Submitted That Met QC Criteria: May 18, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Endometrial cancer; Progesterone Receptor Negative; Recurrent or persistent endometrial carcinoma; Sodium Cridanimod
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Endometrial Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Central Nervous System Stimulants; Interferon Inducers; Appetite Stimulants; Progestins; Megestrol; Megestrol Acetate; 10-carboxymethyl-9-acridanone
• Other Study ID Numbers: VX-EC-2-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No