A Phase 2 interventional study of ESK981 in Castration Levels of Testosterone, Castration-Resistant Prostate Carcinoma and Metastatic Prostate Carcinoma, sponsored by Barbara Ann Karmanos Cancer Institute. Completed at 2 sites in United States. Open to male participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-07-14.
Sponsored by Barbara Ann Karmanos Cancer Institute · Phase 2, Interventional, and Treatment
Among 22 studies in Prostatic Neoplasms by Barbara Ann Karmanos Cancer Institute — 2 open to participants now, 2 under way, none of them phase 3. Prostatic Neoplasms · Barbara Ann Karmanos Cancer Institute.
Among the 22 studies in Prostatic Neoplasms by Barbara Ann Karmanos Cancer Institute, this one is the 15th largest by enrollment of the 19 interventional ones that give a count, is the only one that started in 2018, is one of 11 in phase 2, and was the 18th registered.
7,046 studies on the registry are indexed under Prostatic Neoplasms; 1,580 are open to participants now.
Browse Prostatic Neoplasms studies →2 of the 22 studies in Prostatic Neoplasms by Barbara Ann Karmanos Cancer Institute are open now, in 1 country. Recruiting first, the newest first:
Barbara Ann Karmanos Cancer Institute · Sites in United States
Barbara Ann Karmanos Cancer Institute · Sites in United States
By country, each count listing its studies:
Of the 1,228 Prostatic Neoplasms studies recruiting now, 928 (76%) set no upper age limit and 76 (6%) stop at 75 or younger; 67 take children under 18; 82 take healthy volunteers.
This study: 18 Years and older · male · no healthy volunteers.
The full table on the hub →This tab as a report to print or save as PDF → With an account.
22 studies; the count open now beside each. This study's row is marked.
A study in two phases is counted once above. Listed by phase, each with its combined phases: Phase 1 2 · Phase 2 12 · Phase 3 1
First in 1998; this study’s year is marked. 1 started in 2018.
This study's enrollment of 13 is below the median of 60 across 5,348 interventional studies indexed under Prostatic Neoplasms.
Median enrollment 26 across the 19 interventional studies, 21 across the 2 observational. Of the 19 that completed or were terminated, 11 (58%) have results posted.
This tab as a report to print or save as PDF → With an account.
Barbara Ann Karmanos Cancer Institute is the lead sponsor of 161 studies on the registry; 19 are open to participants now.
Of its 8 completed or terminated interventional studies of FDA-regulated products, 6 (75%) have results posted.
None of the studies under way reaches primary completion within a year.
Among the 22 studies in Prostatic Neoplasms by Barbara Ann Karmanos Cancer Institute, from their registry updates:
This tab as a report to print or save as PDF → With an account.
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.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Current systemic therapy (other than a gonadotrophin releasing hormone [GnRH] agonist/antagonist) for CRPC including:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Brain metastases
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Drug: ESK981
Treatment with ESK981 for patients with metastatic castrate resistant prostate cancer
PSA Decline of >= 50% (PSA50) From Baseline
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.
Time frame: Up to 1 year
Duration of PSA Response (RD)
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.
Time frame: From start of PSA50 until PSA progression, assessed up to 1 year
PSA Progression Free Survival (PFS)
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.
Time frame: Date that a 25% or greater increase and an absolute increase of 2.0 ng/mL or more from the nadir is documented and confirmed by a second value obtained 3 or more weeks later, assessed up to 1 year
Time to PSA Response
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.
Time frame: From treatment start until the first documented occurrence of PSA50, assessed up to 1 year
Androgen Receptor (AR) Signaling
Will examine the association of somatic and germline mutations with exceptional response/resistance to pan-VEGFR/TIE2 tyrosine kinase inhibitor CEP-11981.
Time frame: Up to 1 year
Circulating and Disseminated Tumor Cells as Pharmacodynamic Biomarkers
Number of Circulating and disseminated tumor cells per 7.5ml as a pharmacodynamic biomarker.
Time frame: Up to 1 year
ETS/Kinase Gene Fusions
Will examine the association of somatic and germline mutations with exceptional response/resistance to pan-VEGFR/TIE2 tyrosine kinase inhibitor CEP-11981.
Time frame: Up to 1 year
Metastatic Kinome Activity Profiles as Predictive Biomarkers
Description of immunohistochemistry of the kinases, graded 0,1,2,3
Time frame: Up to 1 year
Immunohistochemistry (IHC) of Protein Markers
Ki67, Receptor, CD31, NG2, desmin, PDGFR1/2, VEGFR1/2 immunohistochemistry graded 0, 1, 2, 3
Time frame: Up to 1 year
DNA Sequencing of Prostate Tumor
copy number, Loss of heterozygosity, mutation, amplification, graded 0,1
Time frame: Up to 1 year
| Milestone | Treatment ESK981 |
|---|---|
| Started | 13 |
| Completed | 13 |
| Not completed | 0 |
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.
| percentage of participants | Treatment ESK981 |
|---|---|
| PSA Decline of >= 50% (PSA50) From Baseline | 7.7 (1.7 to 28.2) |
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.
| months | Treatment ESK981 |
|---|---|
| Duration of PSA Response (RD) | 1.9 |
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.
| months | Treatment ESK981 |
|---|---|
| PSA Progression Free Survival (PFS) | 0.9 (0.2 to 1.9) |
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.
| months | Treatment ESK981 |
|---|---|
| Time to PSA Response | 10.0 |
Will examine the association of somatic and germline mutations with exceptional response/resistance to pan-VEGFR/TIE2 tyrosine kinase inhibitor CEP-11981.
No measurements were reported for this outcome.
Number of Circulating and disseminated tumor cells per 7.5ml as a pharmacodynamic biomarker.
No measurements were reported for this outcome.
Will examine the association of somatic and germline mutations with exceptional response/resistance to pan-VEGFR/TIE2 tyrosine kinase inhibitor CEP-11981.
No measurements were reported for this outcome.
Description of immunohistochemistry of the kinases, graded 0,1,2,3
No measurements were reported for this outcome.
Ki67, Receptor, CD31, NG2, desmin, PDGFR1/2, VEGFR1/2 immunohistochemistry graded 0, 1, 2, 3
No measurements were reported for this outcome.
copy number, Loss of heterozygosity, mutation, amplification, graded 0,1
No measurements were reported for this outcome.
Collected over 2 years. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Treatment ESK981 | 10/13 (76.9%) | 5/13 (38.5%) | 13/13 (100%) |
| Event | Treatment ESK981 |
|---|---|
| Cardiac disorders - Other, specifyCardiac disorders | 2/13 |
| Alanine aminotransferase increasedInvestigations | 1/13 |
| Aspartate aminotransferase increasedInvestigations | 1/13 |
| DehydrationMetabolism and nutrition disorders | 1/13 |
| DiarrheaGastrointestinal disorders | 1/13 |
| HyperglycemiaMetabolism and nutrition disorders | 1/13 |
| HypertensionVascular disorders | 1/13 |
| HyponatremiaMetabolism and nutrition disorders | 1/13 |
| HypotensionVascular disorders | 1/13 |
| Lymphocyte count decreasedInvestigations | 1/13 |
| Event | Treatment ESK981 |
|---|---|
| Back painMusculoskeletal and connective tissue disorders | 4/13 |
| FatigueGeneral disorders | 4/13 |
| PainGeneral disorders | 4/13 |
| Gastrointestinal disorders - Other, specifyGastrointestinal disorders | 3/13 |
| ConstipationGastrointestinal disorders | 2/13 |
| DiarrheaGastrointestinal disorders | 2/13 |
| HypertensionVascular disorders | 2/13 |
| Localized edemaGeneral disorders | 2/13 |
| Musculoskeletal and connective tissue disorderMusculoskeletal and connective tissue disorders | 2/13 |
| Pain in extremityMusculoskeletal and connective tissue disorders | 2/13 |
| Age, Continuous(years) | Treatment ESK981 |
|---|---|
| Median | 71 (58 to 84) |
| Sex: Female, Male(Participants) | Treatment ESK981 |
|---|---|
| Female | 0 |
| Male | 13 |
| Race (NIH/OMB)(Participants) | Treatment ESK981 |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 0 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 4 |
| White | 9 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
| Region of Enrollment(participants) | Treatment ESK981 |
|---|---|
| United States | 13 |
| Performance Status(Participants) | Treatment ESK981 |
|---|---|
| PS = 1 | 13 |
| PS = 0 | 0 |
| Gleason Score(Participants) | Treatment ESK981 |
|---|---|
| Gleason Score 6 | 1 |
| Gleason Score 7 | 3 |
| Gleason Score 8~10 | 6 |
| Gleason Score unknown | 3 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No
Ran from Mar 2018 to primary completion in Mar 2023, 60 months.
Results were first posted in Jul 2023, 3 months after primary completion.
Of 610 non-industry phase 2 interventional studies under Prostatic Neoplasms, half reached primary completion within 57 months of starting (the median), counting those still running; a quarter within 39 and three quarters within 86. This study's 60 months is close to that.
Counting every sponsor, half of 724 studies reached it within 53 months; a quarter within 34 and three quarters within 80.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Jun 2023. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
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Studies of the drug tested here: Cep-11981
Barbara Ann Karmanos Cancer Institute →