ESK981 for Cancer

Recruiting in Palo Alto (17 mi)

+2 other locations

Overseen by Vaibhav Sahai, MBBS, MS

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of Michigan Rogel Cancer Center

Must not be taking: CYP inhibitors

Disqualifiers: Cerebral metastasis, CNS tumor, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This protocol will enroll patients with pancreatic adenocarcinoma and adenosquamous carcinoma (Cohort 1), gastrointestinal/pancreatic neuroendocrine neoplasms with Ki-67 \> 20% (Cohort 2) and neuroendocrine prostate carcinoma (Cohort 3)). Each cohort will have its own interim analysis after enrollment of 10 patients. Subjects will be given a one-month (28 day) supply of study drug (ESK981). Subjects will be instructed to take 4 capsules, with or without food, once per day for 5 consecutive calendar days, then take a drug holiday for 2 consecutive days before repeating the 5 days on-2 days off cycle in sets of 4 weeks or 28 calendar days. Subjects will be asked to keep a pill diary noting the date they take their study drug.

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.

What makes the drug ESK981 unique for cancer treatment?

The drug ESK981 is unique because it targets specific pathways involved in cancer cell survival and resistance, potentially offering a novel approach to overcoming chemoresistance in certain types of cancer, such as mesenchymal lung cancer, by interfering with the MEK1/MP1/ERK1/BCL2 axis. ^{1 2 3 4 5}

Research Team

Vaibhav Sahai, MBBS, MS

Principal Investigator

University of Michigan

Eligibility Criteria

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

Trial Timeline

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

Treatment Details

Interventions

• ESK981 (Other)

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.

Participant Groups

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+

Marschall S. Runge

University of Michigan Rogel Cancer Center

Chief Executive Officer since 2015

MD, PhD

Eric R. Fearon

University of Michigan Rogel Cancer Center

Chief Medical Officer since 2016

MD, PhD

Findings from Research

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]

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]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

BCL2 induced by LAMTOR3/MAPK is a druggable target of chemoradioresistance in mesenchymal lung cancer. [2021]

2. United States 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. [2018]

3. United States 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. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Simultaneous exposure of transformed cells to SRC family inhibitors and CHK1 inhibitors causes cell death. [2021]

5. New Zealand pubmed.ncbi.nlm.nih.gov

ZD1839 ('Iressa') as an anticancer agent. [2018]