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Prostate AdenocarcinomaPhase 1NCT03829930

Combination of Entinostat and Enzalutamide in Advanced Prostate Cancer

A Phase 1 study testing Entinostat and Enzalutamide in people with Prostate Adenocarcinoma, run by George Washington University at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

To determine the safety and tolerability of Entinostat in combination with Enzalutamide in metastatic castrate resistant prostate cancer Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Prostate Adenocarcinoma
What is being tested?
Entinostat and Enzalutamide
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
1 siteUnited States
Study dates
1 May 2019to 1 Sep 2020
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Each patient must meet all of the following inclusion criteria to be enrolled in the study:
  • Age >/= 18 years and are capable of giving informed consent. Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
  • Patients must have a pathologically confirmed diagnosis of prostate adenocarcinoma. Features of neuroendocrine phenotype are allowed.
  • Patients must have evidence of castration resistant metastatic disease and eligible for Enzalutamide per standard guidelines. Castration resistant non-metastatic disease is allowed in phase I study if subject is candidate for Enzalutamide.
  • Patients must have and ECOG performance status of ≤ 2.(appendix D)
  • Patients must be on continuous LHRH agonist or antagonist treatment or surgically castrated with castrate levels of testosterone (< 20 ng/dl).
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  • Any number of prior chemotherapy regimens are allowed. Chemotherapy naïve patients are allowed.
  • If patient is already on Enzalutamide at a dose of 160mg daily, he is allowed if he can have baseline image and PSA within 1 month of the start of entinostat.
  • Patients may have had androgen synthesis inhibitors or other investigational drugs. Patient must have discontinued flutamide or nilutamide or other AR targeted agents (including abiraterone) for at least 4 weeks and bicalutamide for at least 6 weeks prior to day 1 of treatment.
  • Patients receiving treatment with bisphosphonates or denosumab must remain on treatment during the study.
  • Patients must not require concurrent radiation or other chemotherapy while receiving protocol therapy. Patients may have received previous radiation but must have completed radiation at least 4 weeks (8 weeks for radiation to the brain) prior to registration.
  • Patients must have recovered to grade ≤ 1 from all acute toxicity of previous radiation, hormonal or chemotherapy treatments.
  • Patient agrees to use an acceptable method for contraception during the entire study treatment period through 4 months after the last dose of entinostat.
  • Adequate renal function as defined by serum creatinine ≤ 1.5 x ULN. If creatinine >1.5 x ULN, calculated or measured creatinine clearance must be ≥ 60 mL/minute (Cockcroft-Gault).
  • ANC > 1500/mm³, platelets > 100,000/mm³, Hgb > 9 g/dL.
  • Total bilirubin ≤ ULN, SGOT (AST) and SGPT (ALT)< 1.5 x ULN. AST and/or ALT may be up to 5X ULN in the setting of known liver metastasis.

Who cannot join

  • Patients meeting any of the following exclusion criteria are not to be enrolled in the study:
  • Patient was treated and discontinued Enzalutamide previously for any reason.
  • Major surgery within 28 days or serious infection requiring IV antibiotics within 14 days preceding the first dose of study treatment
  • Patient has received other investigational drugs within 14 days before enrollment.
  • Known GI disease or GI procedure that could impact drug absorption in the upper bowel, or tolerance of Entinostat. Examples include but are not limited to partial gastrectomy, small bowel resection, pancreatectomy, malabsorption or celiac disease
  • Ongoing nausea or vomiting of any severity without improvement after appropriate treatment.
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  • > Grade 1 diarrhea, not controlled with appropriate treatment.
  • History of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease requiring supplemental oxygen.
  • Clinical and/or radiographic evidence of cerebral metastases. However, patients who have a history of central nervous system (CNS) metastasis but who have no radiographic or clinical evidence of residual tumor (eg, following complete surgical resection or stereotactic radiosurgery) are not excluded from participation in this study.
  • Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any EKG abnormality at Screening has to be documented by the investigator as not medically relevant.
  • Serious medical or psychiatric illness or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for enrollment in this study.
  • Any other currently active malignancy (excluding controlled non-melanoma skin cancer). Patients are considered NOT to have "currently active" malignancy if they have completed any necessary therapy and are considered by their physician to be at less than 30% risk of relapse.
  • Treatment with clinically significant enzyme inducers, such as the enzyme-inducing antiepileptic drugs phenytoin, carbamazepine or phenobarbital, or rifampin, rifabutin, rifapentine or St. John's Wort within 14 days prior to the first dose of Entinostat and during the study.
  • History of seizure and on active therapy for seizure
  • Known history of uncontrolled human immunodeficiency virus (HIV) infection. HIV positive patients will be allowed if they are on treatment and have an adequate CD4 count (CD4 count >200). Screening is not required in the absence of clinical findings or suspicion.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • George Washington University - Medical Faculty Associates

    Washington D.C., District of Columbia, 20037

Other trials in United States

About this study

Official title: A Phase I Study of Entinostat in Combination With Enzalutamide for Treatment of Patients With Castration-Resistant Prostate Cancer

To determine the safety and tolerability of Entinostat in combination with Enzalutamide in metastatic castrate resistant prostate cancer

Read the detailed description

This study is designed to determine the safety and tolerability of Entinostat with Enzalutamide for treatment of patients with castration-resistant prostate cancer. There will be two dose levels of Entinostat in combination with same dose of Enzalutamide. Patients will be followed during treatment and 1 month post discontinuation.

Being tested
Entinostat, Enzalutamide
Keywords
Castration resistant prostate cancer

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EntinostatDrug

    Also called SYND-275 amd MS-275

    Entinostat is formulated for oral administration. A food effect is evident for entinostat; exposure is significantly reduced when entinostat is administered with a high fat meal. Accordingly, entinostat is to be administered on an empty stomach, at least 1 hour before and 2 hours after a meal. Entinostat tablets should not be split, crushed, or chewed. Consult the individual clinical protocols for specific dosing instructions.

    Dose level 1: 3mg PO weekly. Dose level 2: 5mg PO weekly.

  • EnzalutamideDrug

    Also called MDV3100

    Dose level 1: 160 mg PO daily. Dose level 2: 160 mg PO daily.

Study groups in NCT03829930
Study groupRoleWhat they receive
Entinostat and EnzalutamideExperimentalEntinostat and Enzalutamide
Receives: Drug: Entinostat; Drug: Enzalutamide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Determination of a suitable dose of Entinostat in combination with Enzalutamide

    Number of participants who experience an adverse event assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

    Measured: 18 months

Secondary outcomes (2)

  1. Progression Free Survival

    Number of participants who survive without disease progression

    Measured: 3 years

  2. Changes in circulating T cell subtype, peripheral blood mononuclear cell (PBMC) H3 acetylation, and phenotype of circulating Tregs

    Analysis of immunomodulatory effects of Entinostat

    Measured: 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Feb 2019
  2. Study start1 May 2019
  3. Primary completion1 Sep 2020
  4. Study completion1 Sep 2020

Why it stopped: Sponsor discontinued the drug

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Model description
3+3 Design
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03829930
Sponsor's protocol ID
GWCC 1000
Status last verified
Jul 2021
First submitted
26 Jan 2019
Last updated
2 Aug 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018 Jan;68(1):7-30. doi: 10.3322/caac.21442. Epub 2018 Jan 4.

    PubMed 29313949

  • Scher HI, Halabi S, Tannock I, Morris M, Sternberg CN, Carducci MA, Eisenberger MA, Higano C, Bubley GJ, Dreicer R, Petrylak D, Kantoff P, Basch E, Kelly WK, Figg WD, Small EJ, Beer TM, Wilding G, Martin A, Hussain M; Prostate Cancer Clinical Trials Working Group. Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol. 2008 Mar 1;26(7):1148-59. doi: 10.1200/JCO.2007.12.4487.

    PubMed 18309951

  • D'Amico AV, Whittington R, Malkowicz SB, Schultz D, Blank K, Broderick GA, Tomaszewski JE, Renshaw AA, Kaplan I, Beard CJ, Wein A. Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA. 1998 Sep 16;280(11):969-74. doi: 10.1001/jama.280.11.969.

    PubMed 9749478

  • Lytton B. Prostate cancer: a brief history and the discovery of hormonal ablation treatment. J Urol. 2001 Jun;165(6 Pt 1):1859-62. No abstract available.

    PubMed 11371867

  • Carroll PR, Kantoff PW, Balk SP, Brown MA, D'amico AV, George DJ, Grossfeld GD, Johnson CS, Kelly WK, Klotz L, Lee WR, Lubeck DP, Mcleod DG, Oh WK, Pollack A, Sartor O, Smith MR, Hart C; Second International Conference on Newer Approaches to Androgen Deprivation Therapy (ADT) in Prostate Cancer. Overview consensus statement. Newer approaches to androgen deprivation therapy in prostate cancer. Urology. 2002 Sep;60(3 Suppl 1):1-6. doi: 10.1016/s0090-4295(02)01559-5. No abstract available.

    PubMed 12231036

  • Denis L, Murphy GP. Overview of phase III trials on combined androgen treatment in patients with metastatic prostate cancer. Cancer. 1993 Dec 15;72(12 Suppl):3888-95. doi: 10.1002/1097-0142(19931215)72:12+3.0.co;2-b. No abstract available.

    PubMed 8252511

  • Hellerstedt BA, Pienta KJ. The current state of hormonal therapy for prostate cancer. CA Cancer J Clin. 2002 May-Jun;52(3):154-79. doi: 10.3322/canjclin.52.3.154.

    PubMed 12018929

  • Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, Oudard S, Theodore C, James ND, Turesson I, Rosenthal MA, Eisenberger MA; TAX 327 Investigators. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004 Oct 7;351(15):1502-12. doi: 10.1056/NEJMoa040720.

    PubMed 15470213

  • de Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels JP, Kocak I, Gravis G, Bodrogi I, Mackenzie MJ, Shen L, Roessner M, Gupta S, Sartor AO; TROPIC Investigators. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet. 2010 Oct 2;376(9747):1147-54. doi: 10.1016/S0140-6736(10)61389-X.

    PubMed 20888992

  • Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, Redfern CH, Ferrari AC, Dreicer R, Sims RB, Xu Y, Frohlich MW, Schellhammer PF; IMPACT Study Investigators. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010 Jul 29;363(5):411-22. doi: 10.1056/NEJMoa1001294.

    PubMed 20818862

  • Small EJ, Schellhammer PF, Higano CS, Redfern CH, Nemunaitis JJ, Valone FH, Verjee SS, Jones LA, Hershberg RM. Placebo-controlled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer. J Clin Oncol. 2006 Jul 1;24(19):3089-94. doi: 10.1200/JCO.2005.04.5252.

    PubMed 16809734

  • de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, Chi KN, Jones RJ, Goodman OB Jr, Saad F, Staffurth JN, Mainwaring P, Harland S, Flaig TW, Hutson TE, Cheng T, Patterson H, Hainsworth JD, Ryan CJ, Sternberg CN, Ellard SL, Flechon A, Saleh M, Scholz M, Efstathiou E, Zivi A, Bianchini D, Loriot Y, Chieffo N, Kheoh T, Haqq CM, Scher HI; COU-AA-301 Investigators. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011 May 26;364(21):1995-2005. doi: 10.1056/NEJMoa1014618.

    PubMed 21612468

  • Knudsen KE, Scher HI. Starving the addiction: new opportunities for durable suppression of AR signaling in prostate cancer. Clin Cancer Res. 2009 Aug 1;15(15):4792-8. doi: 10.1158/1078-0432.CCR-08-2660. Epub 2009 Jul 28.

    PubMed 19638458

  • Nelson PS. Molecular states underlying androgen receptor activation: a framework for therapeutics targeting androgen signaling in prostate cancer. J Clin Oncol. 2012 Feb 20;30(6):644-6. doi: 10.1200/JCO.2011.39.1300. Epub 2011 Dec 19. No abstract available.

    PubMed 22184375

  • Tran C, Ouk S, Clegg NJ, Chen Y, Watson PA, Arora V, Wongvipat J, Smith-Jones PM, Yoo D, Kwon A, Wasielewska T, Welsbie D, Chen CD, Higano CS, Beer TM, Hung DT, Scher HI, Jung ME, Sawyers CL. Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science. 2009 May 8;324(5928):787-90. doi: 10.1126/science.1168175. Epub 2009 Apr 9.

    PubMed 19359544

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Entinostat and Enzalutamide in people with Prostate Adenocarcinoma, run by George Washington University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 2 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Sponsor discontinued the drug). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Determination of a suitable dose of Entinostat in combination with Enzalutamide (time frame: 18 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03829930, which also lists 30 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Aug 2021.

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