Advanced or Recurrent Ovarian, Cervical, and Endometrial Cancer Treated With SHetA2 (Okgyn1)

• ClinicalTrials.gov Identifier: NCT04928508
• Recruitment Status: Recruiting
• First Posted: June 16, 2021
• Last Update Posted: July 8, 2022
• Sponsor: University of Oklahoma
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): University of Oklahoma

Tracking Information

• First Submitted Date: June 10, 2021
• First Posted Date: June 16, 2021
• Last Update Posted Date: July 8, 2022
• Actual Study Start Date: June 27, 2022
• Estimated Primary Completion Date: November 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 10, 2021)

• Number of dose-limiting toxicities of treatment with SHetA2 [ Time Frame: 21 days ]
• Dosage Recommendation for Phase 2 [ Time Frame: 21 days ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 10, 2021)

• Rate of objective response [ Time Frame: up to three years ]
• Median duration of response [ Time Frame: up to three years ]
• Rate of disease control [ Time Frame: up to three years ]
• Median progression free survival [ Time Frame: up to three years ]
• Median overall survival [ Time Frame: up to three years ]
• Incidence of adverse events [ Time Frame: up to three years ]
  safety and tolerability of SHetA2 using Common Terminology Criteria for Adverse Events (CTCAE) v.5.0
• Tmax of PK plasma concentration [ Time Frame: 24 hours ]
• Cmax of PK plasma concentration [ Time Frame: 24 hours ]
• AUC of PK plasma concentration [ Time Frame: 24 hours ]
• t1/2 of PK plasma concentration [ Time Frame: 24 hours ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Advanced or Recurrent Ovarian, Cervical, and Endometrial Cancer Treated With SHetA2
• Official Title: Phase 1 Trial of SHetA2 in Patients With Advanced or Recurrent Ovarian, Cervical, and Endometrial Cancer
• Brief Summary: The purpose of this research is to test the safety of the study drug (SHetA2) and see what effects (good and bad) this drug has on patients with recurrent cervical, ovarian, or endometrial cancer.
• Detailed Description: SHetA2 capsules will be given twice a day, every day in 21-day blocks of time. Each block of time is called a cycle. The cycle will be repeated until the patient or doctor no longer feel participation in the study is right for the patient. There will be lab tests and examinations to monitor the patients progress. We expect that taking part in this research will last up to three years.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Ovarian Cancer
• Endometrial Cancer
• Cervix Cancer

Intervention

Drug: SHetA2

SHetA2 orally in the form of 50 mg capsules. Four dose levels will be evaluated:

5.4mg/kg 7.0mg/kg 9.0mg/kg 12mg/kg

Other Name: NSC 726189

Study Arms

Experimental: SHetA2 capsule

SHetA2 (oral, BID) within a 21-days cycle

Intervention: Drug: SHetA2

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 10, 2021): 50
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: February 2024
• Estimated Primary Completion Date: November 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patients must have histologic diagnosis of epithelial ovarian, fallopian tube, or primary peritoneal carcinoma which is considered platinum resistant (recurrence < 6 months from last platinum treatment or for whom platinum therapy is no longer considered appropriate). Histologic documentation of the original primary tumor is required via the pathology report.

NOTE: Patients with the following histologic ovarian epithelial cell types are eligible:

High grade serous adenocarcinoma, endometrioid adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, or adenocarcinoma not otherwise specified (N.O.S.).

Or

Patients with recurrent cervical cancer and who have progressed following or refused platinum based therapy. Squamous, adenocarcinomas and adenosquamous cancers are eligible. Other histologies will be considered if HPV related.

Or

Patients with histologically-documented carcinoma of the endometrium, including endometrioid, serous, mixed adenocarcinoma, clear-cell carcinoma, or carcinosarcoma. Evidence that the endometrial cancer is advanced, recurrent, or persistent and has relapsed or is refractory to curative therapy or established treatments.

Patients must have adequate:

• Bone marrow function as defined per protocol
• Renal function as defined per protocol
• Hepatic function as defined per protocol
• International normalized ratio (INR) or prothrombin time (PT) ≤1.5x ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
• Activated partial thromboplastin time (aPTT) ≤1.5x ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• Neurologic function: Neuropathy (sensory and motor) less than or equal to Grade 1. Patients should be free of active infection requiring parenteral antibiotics or a serious uncontrolled medical illness or disorder within four weeks of study entry.
• Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration. Continuation of hormone replacement therapy is permitted.
• Patients must have a performance status score of 0-2 by Eastern Cooperative Group (ECOG) criteria.
• Patients of childbearing potential must have a negative pregnancy test prior to the study entry and be practicing an effective form of contraception. If applicable, patients must discontinue breastfeeding prior to study entry.
• Patients must have satisfactory results for the baseline laboratory analyses and diagnostic procedures as specified in the protocol
• Patients must have signed an IRB-approved informed consent and authorization permitting release of personal health information.
• Patients must be at least 18 years old.
• Patients in all cohorts must have a fresh pre-treatment tumor biopsy.
• Patients must be willing to have fresh biopsy taken post-Cycle 1 treatment
• Life expectancy of at least 3 months.
• Patients must be able to take oral medications.
• 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.

Exclusion Criteria:

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to SHetA2.
• A diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Patients receiving treatment for active autoimmune disease. "Active" refers to any condition currently requiring therapy. Examples of autoimmune disease include systemic lupus erythematosus, multiple sclerosis, inflammatory bowel disease and rheumatoid arthritis. (note if steroid use is <10mg/day prednisolone equivalent and patient has stable symptoms they may be allowed on study with discussion with the medical monitor)
• Patients with a prior or concurrent malignancy whose natural history or treatment does have the potential to interfere with the safety or efficacy assessment of the investigational regimen are NOT eligible for this trial.
• Known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus ribonucleic acid [HCV RNA] [qualitative] is detected). Ongoing systemic bacterial, fungal, or viral infection; known human immunodeficiency virus (HIV) infection with positive viral load or acquired immunodeficiency syndrome (AIDS)-related illness. Patients with HIV and a negative viral load are allowed on study.
• Patients with concurrent severe medical problems unrelated to the malignancy that would significantly limit full compliance with the study or expose the patient to extreme risk or decreased life expectancy.
• Patients with history or evidence upon physical examination of CNS disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first date of treatment on this study.

NOTE: Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging (using the identical imaging modality for each assessment, either magnetic resonance imaging [MRI] or computed tomography [CT] scan) for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. Carcinomatous meningitis precludes a patient from study participation regardless of clinical stability

• Patients taking concomitant therapy with any of the following: other non-study cytotoxic chemotherapy; other investigational therapies.
• Prior bone marrow/hematopoietic stem cell transplantation
• History of solid organ, bone marrow, or progenitor cell transplantation
• History of major surgical procedure within 28 days prior to start of study treatment

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Ingrid Block; 1-405-271-8777; SCC-IIT-Office@ouhsc.edu

Contact: Lead Gynecology Oncology Nurse; 1-405-271-8777; SCC-IIT-Office@ouhsc.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04928508
• Other Study ID Numbers: Okgyn1; R01CA196200 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: University of Oklahoma
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Oklahoma
• Original Study Sponsor: Same as current
• Collaborators: National Cancer Institute (NCI)

Investigators

• Principal Investigator: Kathleen Moore, MD; Stephenson Cancer Center

• PRS Account: University of Oklahoma
• Verification Date: July 2022