ESK981 for Cancer

Recruiting at 2 trial locations

Overseen By Cancer AnswerLine

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Michigan Rogel Cancer Center

Must not be taking: CYP inhibitors

Disqualifiers: Cerebral metastasis, CNS tumor, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 4 months

66 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, ESK981, for certain advanced cancers, including specific pancreatic and prostate cancers. The goal is to determine if ESK981 can help when other treatments have failed or are intolerable. Participants will take capsules of the study drug on a specific schedule each month. The trial seeks individuals with particular types of advanced pancreatic or prostate cancers that have not responded well to standard treatments. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications for the ESK981 cancer trial?

The trial requires that you do not use any chronic daily medication known to be a strong or moderate inhibitor of certain enzymes (CYP1A2, CYP2C8, or CYP3A4). If you are taking such medications, you may need to stop them. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

Is there any evidence suggesting that ESK981 is likely to be safe for humans?

Research has shown that ESK981, a drug tested for various cancers, has demonstrated promise in earlier studies. ESK981 targets specific proteins that can aid cancer growth.

In studies with patients who had advanced cancers, ESK981 was generally well-tolerated, with most people not experiencing severe side effects. However, while the drug was safe for many, it did not consistently shrink tumors, particularly in some patients with prostate cancer.

For those considering joining the trial, it is reassuring that ESK981 has been tested in humans before and has a good overall safety record. However, like any medication, side effects may occur, and responses can vary. Discussing potential risks and benefits with a doctor is always advisable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cancer?

Researchers are excited about ESK981 because it targets cancer in a new way compared to standard chemotherapy and targeted therapies. ESK981 works by inhibiting angiogenesis, the process by which tumors develop new blood vessels to grow and spread. This is different from typical treatments like chemotherapy, which directly kill cancer cells but can also affect healthy cells. By starving the tumor of its blood supply, ESK981 may offer a more targeted and potentially less harmful approach to treating aggressive cancers like pancreatic adenocarcinoma, high Ki-67 neuroendocrine tumors, and neuroendocrine prostate carcinoma.

What evidence suggests that ESK981 might be an effective treatment for cancer?

Research shows that ESK981, a type of drug, may help treat various cancers. In this trial, participants will divide into different cohorts based on their cancer type. In Cohort 1, researchers are studying ESK981 for its potential to treat pancreatic adenocarcinoma. Studies suggest that ESK981 can slow tumor growth by blocking important pathways that cancer cells need to multiply. Participants in Cohort 2, with pancreatic or gastrointestinal neuroendocrine tumors, will also receive ESK981, and early findings indicate it might help control cancer progression. For Cohort 3, focusing on neuroendocrine prostate carcinoma, evidence suggests ESK981 could be effective by targeting several growth-related pathways. While more research is needed to confirm these results, the early data is promising for these types of cancer. ^{3 6 7 8 9}

Who Is on the Research Team?

Vaibhav Sahai, MBBS, MS

Principal Investigator

University of Michigan

Are You a Good Fit for This Trial?

This trial is for adults with certain advanced cancers, including pancreatic adenocarcinoma, gastrointestinal/pancreatic neuroendocrine tumors with high Ki-67 levels, and neuroendocrine prostate carcinoma. Participants must have progressed beyond or be intolerant to standard treatments and meet specific criteria like having visceral metastases or a high volume of disease.

Inclusion Criteria

Willing to provide archived tissue, if available, from a previous diagnostic biopsy

My advanced cancer type has been confirmed by lab tests.

Ability to understand and willingness to sign IRB-approved informed consent

Exclusion Criteria

I have not had cancer before, except for certain types.

My blood pressure is controlled and below 150/90.

Patient is living outside the US

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ESK981 for 5 consecutive days followed by a 2-day drug holiday, repeated in 4-week cycles

4 months

Monthly visits for drug supply and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 18 months

What Are the Treatments Tested in This Trial?

Interventions

• ESK981

Trial Overview The study tests ESK981 in patients across three cohorts based on their cancer type. Patients take the drug orally for five days followed by a two-day break, repeating this cycle every four weeks while keeping track of their medication intake in a diary.

How Is the Trial Designed?

Group I: Cohort 3 Experimental Treatment 1 Intervention

Neuroendocrine prostate carcinoma with Ki-67 \> 20%

Group II: Cohort 2 Experimental Treatment 1 Intervention

Pancreatic or gastrointestinal neuroendocrine neoplasms with Ki-67 \> 20%

Group III: Cohort 1 Experimental Treatment 1 Intervention

Pancreatic adenocarcinoma

Who Is Running the Clinical Trial?

University of Michigan Rogel Cancer Center

Lead Sponsor

Trials

303

Recruited

20,700+

Published Research Related to This Trial

CHK1 inhibitors, when combined with MEK1/2 inhibitors, effectively kill breast cancer cells and transformed fibroblasts, indicating a potential therapeutic strategy for targeting these cancer types.

The lethality of CHK1 inhibitors is linked to the activation of SRC family kinases, and the effectiveness of these treatments can be enhanced by using BCL-2/BCL-XL antagonists, suggesting a complex interplay between these pathways in cancer cell death.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simultaneous exposure of transformed cells to SRC family inhibitors and CHK1 inhibitors causes cell death. Mitchell, C., Hamed, HA., Cruickshanks, N., et al.[2021]

BCL2 expression is linked to poor prognosis and chemoresistance in mesenchymal-type lung cancers, indicating it as a potential target for treatment.

Combination therapies using BH3 mimetics like ABT-263 and ABT-737 can effectively reduce chemoresistance in mesenchymal lung cancer cells, suggesting that targeting the MEK1/MP1/ERK1/BCL2 pathway could improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BCL2 induced by LAMTOR3/MAPK is a druggable target of chemoradioresistance in mesenchymal lung cancer. Kwon, OS., Hong, SK., Kwon, SJ., et al.[2021]

V158411, a selective Chk1 inhibitor, significantly upregulates the BCL2A1 gene in U2OS cells, increasing its mRNA levels over 400-fold, which is not observed in other cell lines like HT29.

The increase in BFL1 protein in U2OS cells, which is linked to the PI3K/AKT/mTOR/MEK signaling pathway, does not prevent apoptosis in response to V158411, indicating that high BFL1 levels do not confer resistance to cell death from Chk1 inhibition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chk1 inhibitor-induced DNA damage increases BFL1 and decreases BIM but does not protect human cancer cell lines from Chk1 inhibitor-induced apoptosis. Massey, AJ.[2023]

ZD1839 ('Iressa') is a selective inhibitor of the epidermal growth factor receptor that effectively blocks cancer cell growth and survival, showing promising results in preclinical studies with various tumor cell lines and human tumor xenografts.

Preliminary phase I trials indicate that ZD1839 is well-tolerated and shows clinical efficacy, especially in non-small cell lung cancer (NSCLC), leading to its ongoing phase III development for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ZD1839 ('Iressa') as an anticancer agent. Baselga, J., Averbuch, SD.[2018]

ZD1839 (Iressa) effectively inhibits the growth of renal cell carcinomas (RCC) by reducing cell proliferation and inducing cell cycle arrest, with a significant decrease in tumor growth observed in xenograft models after 3 weeks of treatment.

The drug also reduces angiogenesis, as evidenced by decreased levels of vascular endothelial growth factor and interleukin-8, and a significant reduction in new blood vessel formation in treated tumors, highlighting its dual mechanism of action against RCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulation of tumor growth and tumor induced angiogenesis after epidermal growth factor receptor inhibition by ZD1839 in renal cell carcinoma. Asakuma, J., Sumitomo, M., Asano, T., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11756588/

Phase II trial of multi‑kinase inhibitor ESK981 in patients ... This phase II trial evaluated the efficacy of ESK981 as a single agent in patients with androgen receptor-positive (AR +) metastatic castration- ...

2. cancer.gov cancer.gov/clinicaltrials/NCI-2024-00956

ESK981 for the Treatment of Patients with Select Advanced ... This phase II trial tests the safety and effectiveness of ESK981 in treating patients with solid tumors that may have spread from where they first started.

3. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/466455

Multicenter Trial of ESK981 in Patients With Select Solid ... Cohort 3: The subject has histologically proven prostate cancer who have progressed or deemed intolerant of at least first-line standard of care systemic ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39227508/

Phase II trial of multi-kinase inhibitor ESK981 in patients with ... This phase II trial evaluated the efficacy of ESK981 as a single agent in patients with androgen receptor-positive (AR +) metastatic castration-resistant ...

5. withpower.com withpower.com/trial/esk981-for-cancer-edffc

ESK981 for Cancer This Phase 2 medical study run by University of Michigan Rogel Cancer Center is evaluating whether ESK981 will have tolerable side effects & efficacy for ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05988918

Study Details | NCT05988918 | Multicenter Trial of ESK981 ... Cohort 3: The subject has histologically proven prostate cancer who have progressed or deemed intolerant of at least first-line standard of care systemic ...

7. medchemexpress.com medchemexpress.com/cep-11981.html?srsltid=AfmBOorF3SPk5BOYoC45co383boIqvUhCssZgmSPGnthM0VSEwhfHLVd

CEP-11981 (ESK981) | Tyrosine Kinase Inhibitor CEP-11981(ESK981; BOL 303213X) is an orally active tyrosine kinase inhibitor (TKI), which can target TIE2, VEGFR1-3 and FGFR1, and has potential anti-tumor and ...

8. synapse.patsnap.com synapse.patsnap.com/drug/d72c88c963574530b1c28e718b0118a5

CEP-11981 - Drug Targets, Indications, Patents The primary endpoints were a 50% reduction in prostate-specific antigen (PSA50), and safety. Secondary endpoints included radiographic progression free survival ...

9. urotoday.com urotoday.com/clinical-trials/prostate-cancer/161632-a-phase-ii-multicenter-trial-of-esk981-in-patients-with-select-solid-tumors.html

A Phase II Multicenter Trial of ESK981 in Patients With ... Cohort 3: The subject has histologically proven prostate cancer who have progressed or deemed intolerant of at least first-line standard of care ...