Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma

Carcinoma, Neuroendocrine

Adenocarcinoma

Prostatic Neoplasms

Neuroendocrine Tumors

Carcinoma, Adenosquamous

Carcinoma, Islet Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Neuroendocrine Tumor

Gastro-enteropancreatic Neuroendocrine Tumor

Pancreatic Neuroendocrine Tumor

Neuroepithelioma

Pancreatic Cancer

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

Neuroendocrine prostate carcinoma with Ki-67 \> 20%

160 mg, PO, Once daily 5 days on and 2 days off

ESK981

Cancer AnswerLine

Vaibhav Sahai, MBBS, MS

Vaibhav Sahai

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.

Multicenter Trial of ESK981 in Patients With Select Solid Tumors

A Phase II Multicenter Trial of ESK981 in Patients With Select Solid Tumors

Determining efficacy using proportion of patients alive and progression-free at 4 months within each cancer subtype

The ORR will be assessed per RECIST v1.1 criteria (Cohort 1 and 2) or combined RECIST v1.1 + PCWG3 criteria (Cohort 3). Partial or complete response will require confirmation on repeat scan at least 4 weeks from initial radiologic response

DoR will be measured from the start date of the best response achieved until the date of relapse (i.e., progression). Continuing responders will be right-censored as of the most recent date on which their response status had been assessed. DoR applies to only the patients who achieve either a complete response or a partial response.

The OS will be defined from the date of treatment to either date of death or censoring and estimated using the product-limit method of Kaplan and Meier. Follow-up time will be censored at the date of last disease evaluation.

Adverse events (AEs) will be defined per the NCI Common Toxicity Criteria for Adverse Events (CTCAE) v5.0.

The PFS will be defined as time from date of initial treatment to date of radiological or clinical progression (leading to withdrawal from the study treatment), or death from any cause on study treatment, whichever comes first. Follow-up time will be censored at the date of last disease evaluation.

University of Michigan Rogel Cancer Center

Symptoms and General Pathology

Disease Progression

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

All Drugs and Chemicals

Amino Acids

Endothelial Growth Factors

Mitogens

Tyrosine Kinase Inhibitors

Tyrosine

Patients receive pan-VEGFR/TIE2 (Vascular Endothelial Growth Factor Receptor/angopoeitin receptor2) tyrosine kinase inhibitor CEP-11981 PO QD for 5 days (Monday-Friday). Treatment repeats for up to 8 weeks in the absence of disease progression or unacceptable toxicity. If treatment is successful after 8 weeks, patients may receive up to 6 months of pan-VEGFR/TIE2 tyrosine kinase inhibitor CEP-11981.

Treatment with ESK981 for patients with metastatic castrate resistant prostate cancer

Elisabeth I. Heath

This phase II trials studies the side effects and how well ESK981 works in treating patients with castration-resistant prostate cancer that has spread to other places in the body. ESK981 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To determine the PSA \>= 50% response rate (PSA50) from baseline using the Prostate Cancer Working Group 3 (PCWG3) criteria to pan-VEGFR/TIE2 tyrosine kinase inhibitor CEP-11981 (ESK981) as a single agent in men with castration-resistant prostate cancer (CRPC) who have progressed on enzalutamide (an oral androgen-receptor inhibitor) and/or abiraterone acetate (an androgen synthesis inhibitor).

II. To assess the safety and tolerability of ESK981 as a single agent.

SECONDARY OBJECTIVES:

I. To determine the time to PSA response to ESK981 in metastatic CRPC patients. II. To determine the duration of PSA response to ESK981 in metastatic CRPC patients.

III. To determine PSA progression rates and PSA progression free survival (PFS), as defined by the PCWG3 criteria.

TERTIARY OBJECTIVES:

I. To assess exploratory biomarkers from blood and tumor biopsies.

OUTLINE:

Patients receive pan-VEGFR/TIE2 tyrosine kinase inhibitor CEP-11981 orally (PO) once daily (QD) for 5 days (Monday-Friday). Treatment repeats for up to 8 weeks in the absence of disease progression or unacceptable toxicity. If treatment is successful after 8 weeks, patients may receive up to 6 months of pan-VEGFR/TIE2 tyrosine kinase inhibitor CEP-11981.

After completion of study treatment, patients are followed up periodically.

ESK981 in Treating Patients With Metastatic Castrate-Resistant Prostate Cancer

An Open-Label, Parallel, Phase II Study of Single-Agent Oral ESK981 in Men With Castrate-Resistant Prostate Cancer (CRPC)

Will examine the association of somatic and germline mutations with exceptional response/resistance to pan-VEGFR/TIE2 tyrosine kinase inhibitor CEP-11981.

Number of Circulating and disseminated tumor cells per 7.5ml as a pharmacodynamic biomarker.

Description of immunohistochemistry of the kinases, graded 0,1,2,3

Ki67, Receptor, CD31, NG2, desmin, PDGFR1/2, VEGFR1/2 immunohistochemistry graded 0, 1, 2, 3

copy number, Loss of heterozygosity, mutation, amplification, graded 0,1

PSA decline of \>= 50% (PSA50) from baseline using Prostate Cancer Working Group 3 (PCWG3) definition with point estimate and (1-sided Wilson type 90% lower) confidence interval (CI) estimates.

Will be summarized with the Kaplan-Meier (K-M) survivorship estimate. A graph of the K-M curve for RD will be generated along with the Hall-Wellner 90% confidence band, and a display of the number of patients at risk at several time points, below the X-axis. Summary statistics (6-month rate, 12-month rate, median, etc.) will be calculated from the K-M life table, each one with its respective 80% CI.

Will be summarized with the Kaplan-Meier (K-M) survivorship estimate. A graph of the K-M curve for PFS will be generated along with the Hall-Wellner 90% confidence band, and a display of the number of patients at risk at several time points, below the X-axis. Summary statistics (6-month rate, 12-month rate, median, etc.) will be calculated from the K-M life table, each one with its respective 80% CI.

Will be used to summarize the time to PSA response. These descriptives will include sample size (N), median, mean, standard deviation (SD), interquartile range (IQR), minimum, and maximum.

National Cancer Institute (NCI)

Barbara Ann Karmanos Cancer Institute

Principal Investigator

An adverse event for the purposes of this protocol is the appearance of (or worsening of any pre-existing) undesirable sign, symptom, or medical condition occurring after signing the informed consent even if the event is not considered to be related to the study drug. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, related or not to the medicinal product.

Patients receive pan-VEGFR/TIE2 (Vascular Endothelial Growth Factor Receptor/angopoeitin receptor2) tyrosine kinase inhibitor CEP-11981 PO QD for 5 days (Monday-Friday). Treatment repeats for up to 8 weeks in the absence of disease progression or unacceptable toxicity. If treatment is successful after 8 weeks, patients may receive up to 6 months of pan-VEGFR/TIE2 tyrosine kinase inhibitor CEP-11981.

ESK981: Treatment with ESK981 for patients with metastatic castrate resistant prostate cancer

Treatment ESK981

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

PS = 1

PS = 0

ECOG Performance Status Scale. Grade 0 to 5. 0=Normal activity, 1=Symptoms but ambulatory, 2=In bed \<50% of the time, 3=In bed \>50% of the time, 4=100% bedridden, 5=Dead

Performance Status

Gleason Score 6

Gleason Score 7

Gleason Score 8~10

Gleason Score unknown

Pathological scores ranging from 2 to 10, with higher numbers indicating greater risks.

Grade 2-4 as well-differentiated tumors, Grade 5-6 as intermediately-differentiated tumors, Grade 7 as moderately to poorly differentiated tumors, Grade 8-10 as "high-grade" tumors.

Gleason Score

Elisabeth Heath, M.D.

PSA Decline of >= 50% (PSA50) From Baseline

patients who achieved a 50% reduction in PSA from baseline

Duration of PSA Response (RD)

PSA Progression Free Survival (PFS)

Time to PSA Response

Androgen Receptor (AR) Signaling

Circulating and Disseminated Tumor Cells as Pharmacodynamic Biomarkers

ETS/Kinase Gene Fusions

Metastatic Kinome Activity Profiles as Predictive Biomarkers

Immunohistochemistry (IHC) of Protein Markers

DNA Sequencing of Prostate Tumor

Overall Study

Carcinoma, Renal Cell

Kidney Neoplasms

Urologic Neoplasms

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Antineoplastic Agents

Nivolumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

ESK981: 160 mg (4 capsules) PO daily for 5 consecutive days followed by a 2-day off drug in each week, repeated weekly in 4-week (28-day) cycles

ESK981: 160 mg (4 capsules) PO daily for 5 consecutive days followed by a 2-day off drug in each week, repeated weekly in 4-week (28-day) cycles

Nivolumab: 480 mg/dose IV, Day 1 of each 28-day cycle

480 mg/dose IV, Day 1 of each 28-day cycle

Ajjai Alva, MD

The objective of the trial is to determine the clinical efficacy of ESK981 in combination with nivolumab therapy in patients with metastatic renal cell carcinoma (RCC).

The study was terminated early due to changes in the RCC treatment landscape which limited the patient population. Due to this early termination no subjects were enrolled into Cohort B.

There are 2 cohorts for accrual with Cohort A being accrued first. Cohort B will follow and will have 2 stages of accrual. Cohort A will accrue 11 patients to monotherapy treatment. Then Cohort B will begin accrual of 17 patients to the first stage and if the interim permits, the second stage will accrue an additional 19 patients.

Multi-center Trial of ESK981 in Combination With Nivolumab in Patients With Metastatic Renal Cell Carcinoma

ERICA: Phase 2 Multi-center Trial of ESK981 in Combination With Nivolumab in Patients With Metastatic Renal Cell Carcinoma

The percentage of patients in Cohort B that achieve a complete response (CR) or partial response (PR). Response will be assessed by combined Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and Immune-related (ir)RECIST.

The percentage of patients in Cohort A that achieve a complete response (CR) or partial response (PR). Response will be assessed by RECIST v1.1.

Overall survival time measured from start of treatment until up to 24 months after the last dose of study treatment in Cohort A (ESK981 monotherapy) and in Cohort B (combination of ESK981 and nivolumab therapy).

Measured from start of treatment to time of progression or death, or up to 24 months after the last dose of study treatment in Cohort A (ESK981 monotherapy) and in Cohort B (combination of ESK981 and nivolumab therapy). Disease progression will be assessed by RECIST v1.1 in Cohort A and by combined RECIST v1.1/irRECIST in Cohort B.

Measured from the first to the last dose of study treatment in Cohort A (ESK981 monotherapy) and in Cohort B (combination of ESK981 and nivolumab therapy).

Measured from the time of complete response (CR) or partial response (PR) (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented. Response will be assessed by RECIST v1.1 (Cohort A) and by combined RECIST v1.1/irRECIST (Cohort B).

ESK981: 160 mg (4 capsules) PO daily for 5 consecutive days followed by a 2-day off drug in each week, repeated weekly in 4-week (28-day) cycles

ESK981: ESK981: 160 mg (4 capsules) PO daily for 5 consecutive days followed by a 2-day off drug in each week, repeated weekly in 4-week (28-day) cycles

ESK981 Monotherapy (Cohort A)

ESK981: 160 mg (4 capsules) PO daily for 5 consecutive days followed by a 2-day off drug in each week, repeated weekly in 4-week (28-day) cycles

Nivolumab: 480 mg/dose IV, Day 1 of each 28-day cycle

ESK981: ESK981: 160 mg (4 capsules) PO daily for 5 consecutive days followed by a 2-day off drug in each week, repeated weekly in 4-week (28-day) cycles

Nivolumab: 480 mg/dose IV, Day 1 of each 28-day cycle

ESK981 and Nivolumab (Cohort B)

ESK981 Monotherapy

ESK981 and Nivolumab

Total

Age, Categorical

Ethnicity (NIH/OMB)

No patients were enrolled in the ESK984 and Nivolumab combo arm

ClinicalTrials.gov Cancer Center Admin

No patients were enrolled in the ESK984 and Nivolumab combo arm (cohort B)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Multicenter Trial of ESK981 in Patients With Select Solid Tumors	NCT05988918	Pancreatic Aden... Adenosquamous C... Pancreatic Neur... Pancreatic Neur... Gastrointestina... Gastrointestina... Neuroendocrine ...	ESK981	18 Years -	University of Michigan Rogel Cancer Center
ESK981 in Treating Patients With Metastatic Castrate-Resistant Prostate Cancer	NCT03456804	Castration Leve... Castration-Resi... Metastatic Pros... PSA Progression Stage IV Prosta...	ESK981	18 Years -	Barbara Ann Karmanos Cancer Institute
Multi-center Trial of ESK981 in Combination With Nivolumab in Patients With Metastatic Renal Cell Carcinoma	NCT03562507	Renal Cell Carc...	ESK981 Nivolumab	18 Years -	University of Michigan Rogel Cancer Center
ESK981 in Treating Patients With Metastatic Castrate-Resistant Prostate Cancer	NCT03456804	Castration Leve... Castration-Resi... Metastatic Pros... PSA Progression Stage IV Prosta...	ESK981	18 Years -	Barbara Ann Karmanos Cancer Institute
ESK981 in Treating Patients With Metastatic Castrate-Resistant Prostate Cancer	NCT03456804	Castration Leve... Castration-Resi... Metastatic Pros... PSA Progression Stage IV Prosta...	ESK981	18 Years -	Barbara Ann Karmanos Cancer Institute
ESK981 in Treating Patients With Metastatic Castrate-Resistant Prostate Cancer	NCT03456804	Castration Leve... Castration-Resi... Metastatic Pros... PSA Progression Stage IV Prosta...	ESK981	18 Years -	Barbara Ann Karmanos Cancer Institute

Spots Global Cancer Trial Database for esk981

Every month we try and update this database with for esk981 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for esk981

Every month we try and update this database with for esk981 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for esk981 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.