SHetA2 for Gynecologic Cancers

(Okgyn1 Trial)

Overseen By Ingrid Block

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: University of Oklahoma

Must not be taking: Immunosuppressants, Steroids, Chemotherapy, others

Disqualifiers: Pregnancy, Autoimmune disease, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: up to three years

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, SHetA2, to assess its safety and effects on individuals with recurrent solid tumors. The focus is on understanding both the positive outcomes and any side effects. Participants should have solid tumors unresponsive to other treatments and must be able to take oral medications. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Will I have to stop taking my current medications?

The trial requires that any hormonal therapy directed at the malignant tumor be stopped at least one week before joining. Other medications, like those for autoimmune diseases or certain investigational therapies, may also need to be stopped, but the protocol does not specify all medications that must be discontinued.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that SHetA2, the active ingredient in the study drug OK-1, has been examined in past studies for its effects on cancer cells. In these studies, SHetA2 changed cancer cell behavior and promoted cell death. While promising, the current clinical trial remains in its early stages, and detailed safety information from human trials is still being collected.

As one of the first trials to test SHetA2 in humans, the primary goal is to assess how well participants tolerate it and identify any side effects. Early-stage trials like this determine safe dosage levels and potential risks. Until more information is available, the safety of SHetA2 is under close observation. ¹

Why do researchers think this study treatment might be promising?

Researchers are excited about SHetA2 for gynecologic cancers because it represents a novel approach compared to current treatments like surgery, chemotherapy, and radiation. SHetA2 works differently by using a small molecule that targets cancer cells with precision, potentially reducing damage to healthy tissues. Additionally, SHetA2 is administered orally in capsule form, making it more convenient and less invasive than traditional therapies that often require intravenous administration or surgical intervention. This innovative mechanism and delivery method offer new hope for more effective and patient-friendly cancer treatment options.

What evidence suggests that SHetA2 might be an effective treatment for gynecologic cancers?

Research shows that SHetA2, the investigational treatment under study in this trial, may help treat certain cancers, such as lung, ovarian, and cervical cancers. Studies have found that SHetA2 can combat cancer with minimal harm to healthy cells. In animal studies, it demonstrated a low risk of side effects, suggesting it might be safer for humans. The drug targets cancer cells and helps stop their growth. Early results are promising, but further research is needed to confirm its benefits for people. ^{2 3 4 5 6}

Who Is on the Research Team?

Debra L. Richardson

Principal Investigator

Stephenson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced or recurrent ovarian, cervical, and endometrial cancers resistant to platinum therapy or other treatments. Participants must have good organ function, no severe infections like HIV with a positive viral load, no recent major surgeries, and not be on certain medications that could affect the study results. They should be able to take oral meds and agree to use contraception if applicable.

Inclusion Criteria

Patients must have satisfactory results for the baseline laboratory analyses and diagnostic procedures as specified in the protocol.

I am willing to undergo a biopsy after the first treatment cycle.

Life expectancy of at least 3 months.

Exclusion Criteria

I have had a transplant of an organ, bone marrow, or stem cells.

I have not taken steroids or immunosuppressants in the last 7 days.

I do not have another cancer that could affect this treatment's safety or results.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive OK-1 capsules twice a day in 21-day cycles

up to three years

Regular lab tests and examinations

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• SHetA2

Trial Overview The trial is testing SHetA2's safety and effectiveness in patients with specific types of cancer that have come back after treatment. It involves taking this investigational drug to see both its positive effects (like shrinking tumors) and any negative ones (side effects).

How Is the Trial Designed?

Group I: OK-1 capsule Experimental Treatment 1 Intervention

OK-1 (oral, BID) within a 21-days cycle

Who Is Running the Clinical Trial?

University of Oklahoma

Lead Sponsor

Trials

484

Recruited

95,900+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Doxorubicin was found to be particularly effective against uterine sarcoma cell lines, while it showed little to no activity against endometrial adenocarcinoma and mixed Mullerian tumor cell lines, indicating a potential need for tailored treatment approaches based on cancer type.

The novel compound SHetA2 demonstrated cytotoxic effects on various uterine cancer cell lines, but it did not enhance the effectiveness of standard chemotherapeutic agents like cisplatin or paclitaxel, suggesting it may be useful as a standalone treatment rather than a combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sensitivities of Uterine Adenocarcinoma, Mixed Mullerian Tumor (MMT) and Sarcoma Cell Lines to Chemotherapeutic Agents and a Flex-Het Drug. Hyde, J., Benbrook, DM.[2021]

Vaginal administration of SHetA2 at a 15 mg/kg dose resulted in cervix concentrations that were about 120 times higher than those achieved with a 60 mg/kg oral dose, indicating a much more effective delivery method for this compound.

The 30 mg/kg vaginal dose not only provided the highest cervix concentration but also significantly reduced cyclin D1 levels, making it the chosen dose for future studies on its efficacy in treating cervical neoplasia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Pharmacodynamics of Escalating Doses of SHetA2 After Vaginal Administration to Mice. Mahjabeen, S., Hatipoglu, MK., Benbrook, DM., et al.[2023]

A screening of 7914 approved drugs revealed that two HDAC inhibitors, mocetinostat and entinostat, effectively suppress various gynecologic cancers, showing promising IC50 values close to their human plasma concentrations.

The study highlights the potential of both known and non-anticancer drugs to inhibit the growth of gynecologic cancer cell lines, suggesting new avenues for therapeutic development and personalized treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative Chemotherapeutic Profiling of Gynecologic Cancer Cell Lines Using Approved Drugs and Bioactive Compounds. Gorshkov, K., Sima, N., Sun, W., et al.[2023]

The combination of SHetA2 and PRIMA-1MET significantly inhibited tumor growth in ovarian cancer models, achieving a 67% tumor-free rate in mice, compared to 0% in controls, indicating a promising maintenance therapy strategy.

This combination therapy specifically targets mutant p53, showing no toxicity in healthy cells, which suggests a safer treatment option for patients with ovarian cancer who have missense mutations in the TP53 gene.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel ovarian cancer maintenance therapy targeted at mortalin and mutant p53. Ramraj, SK., Elayapillai, SP., Pelikan, RC., et al.[2021]

Patient Derived Xenografts (PDXs) from chemotherapy-naïve high-grade serous epithelial ovarian cancer (HGS-EOC) showed responsiveness to drugs like carboplatin, trabectedin, and gemcitabine, indicating potential effectiveness of these agents in untreated cancers.

After initial platinum-based chemotherapy, PDXs from the same patients lost responsiveness to trabectedin and gemcitabine, highlighting the need for personalized treatment strategies as tumor responses can vary significantly post-chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Xenopatients show the need for precision medicine approach to chemotherapy in ovarian cancer. Erriquez, J., Olivero, M., Mittica, G., et al.[2022]

SHetA2 effectively inhibits key cancer behaviors such as growth, migration, and invasion in endometrial cancer cell lines, while also inducing cell death through mitochondrial damage and apoptosis mechanisms.

When combined with paclitaxel, SHetA2 shows a synergistic effect, leading to greater tumor growth inhibition in xenograft models than either drug used alone, suggesting a promising new treatment strategy for advanced endometrial cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utility and Mechanism of SHetA2 and Paclitaxel for Treatment of Endometrial Cancer. Chandra, V., Rai, R., Benbrook, DM.[2021]

SHetA2, a novel anticancer drug, shows selective inhibition of cancer cells over normal cells and has a half-life of 4.5 hours, indicating its potential effectiveness in cancer treatment.

The study developed a physiologically based pharmacokinetic (PBPK) model that revealed SHetA2 has rapid and extensive tissue distribution, with oral bioavailability estimated at 22.3%, which is crucial for predicting its efficacy in tumor treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physiologically Based Pharmacokinetic Modeling and Tissue Distribution Characteristics of SHetA2 in Tumor-Bearing Mice. Sharma, A., Li, M., Thavathiru, E., et al.[2021]

Vaginal administration of SHetA2 results in significantly higher absorption into the cervix (23.9%) compared to oral administration (0.02%), making it a more effective delivery method for treating cervical dysplasia.

Daily vaginal doses of SHetA2 maintained therapeutic drug levels in the cervix for 65 hours and effectively reduced cyclin D1 levels by approximately 45%, indicating both efficacy and safety, as no adverse effects were observed in the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaginal Suppositories Containing SHetA2 to Treat Cervical Dysplasia: Pharmacokinetics of Daily Doses and Preliminary Safety Profile. Mahjabeen, S., Hatipoglu, MK., Kosanke, SD., et al.[2021]

SHetA2 shows a promising safety profile and potential for cancer prevention and treatment, with pharmacokinetic modeling conducted on data from mice, rats, and dogs to predict human absorption and disposition.

The study found that SHetA2's oral bioavailability varies significantly across species and doses, leading to a recommended first-in-human dose that is lower than what toxicology studies suggested, ensuring safety in initial human trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and interspecies scaling of a novel, orally-bioavailable anti-cancer drug, SHetA2. Sharma, A., Benbrook, DM., Woo, S.[2021]

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0731708518319678

Development and validation of a reverse phase HPLC ... SHetA2 is a flexible heteroarotinoid that has the potential to prevent and treat lung, ovarian and cervical cancer without significant toxicity.

2. jscimedcentral.com jscimedcentral.com/jounal-article-info/JSM-Chemistry/SHetA2-%E2%80%93-A-Mini-Review-of-a-Promising-Anticancer-Drug-8860

SHetA2 In summary, SHetA2 (1) has exhibited useful pharmaceutical properties, has low toxicity as determined in mice and dogs, can be quantitatively ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30878829/

Synthesis and Biological Evaluation of SHetA2 (NSC ... Although SHetA2 is scheduled to enter clinical trials in the near future, alternative backup drug candidates have been identified in this work.

4. jscimedcentral.com jscimedcentral.com/public/assets/articles/chemistry-1-1005.pdf

SHetA2 – A Mini Review of a Promising Anticancer Drug The structure is comprised of a sulfur-containing heterocylic ring, a thiourea linker, and a 4-nitrophenyl substituent. SHetA2. (1) showed the ...

5. sciencedirect.com sciencedirect.com/science/article/am/pii/S0223523419302211

Synthesis and biological evaluation of SHetA2 (NSC- ... This agent (Figure. 1) is a Flex-Het that contains a sulfur heterocycle (Ring A) linked via a thiourea unit to a 4'-nitrophenyl moiety. (Ring B) [13,21]. SHetA2 ...

6. ouhsc.edu ouhsc.edu/benbrooklab/Benbrook%20CV%202019%20Activity%20Insight.pdf

Doris Mangiaracina Benbrook, BA, PhD Effects of retinoids on cancerous phenotype and apoptosis in organotypic cultures of ovarian carcinoma. Journal of the National Cancer Institute ...