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Castration Levels of TestosteronePhase 1/2NCT03709550

Enzalutamide and Decitabine in Treating Patients With Metastatic Castration Resistant Prostate Cancer

A Phase 1/2 study testing Decitabine and Enzalutamide in people with Castration Levels of Testosterone and Castration-Resistant Prostate Carcinoma, run by Roswell Park Cancer Institute at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This phase I/II trial studies the side effects and best dose of decitabine and how well it works when given together with enzalutamide in treating patients with castration resistant prostate cancer that has spread to other places in the body. Androgen can cause the growth of prostate cancer cells. Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Decitabine and Enzalutamide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
15 Apr 2021to 15 Apr 2024
Phase
Phase 1/2
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

  • Histological or cytological documentation of diagnosis of prostate cancer, all histological sub-types included.
  • Documented progressive metastatic castrate resistant prostate cancer (mCRPC) based on at least one of the following criteria:
  • PSA progression defined as 25% increase over baseline value with an increase in the absolute value of at least 2 ng/mL that is confirmed by another PSA level with a minimum of a 1week interval and a minimum PSA of 2 ng/mL
  • Soft-tissue progression defined as an increase >= 20% in the sum of the longest diameter (LD) of all target lesions based on the smallest sum LD since treatment started or the appearance of one or more new lesions
  • Progression of bone disease (evaluable disease) or (new bone lesion[s]) by bone scan
  • If on an anti-androgen, must have documented progression 6 weeks after stopping anti-androgen therapy
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  • Willing to undergo a biopsy, if readily available biopsy site present, i.e., nodal or visceral metastasis (if adequate formalin-fixed, paraffin-embedded (FFPE) archival mCRPC samples are not available (or biopsy was taken longer than 6 months from start of study treatment), a fresh pre-treatment mCRPC biopsy needs to be obtained)
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  • Have testosterone < 50 ng/dL. Note: Patients must continue primary androgen deprivation with an luteinizing hormone-releasing hormone (LHRH) analogue (agonist or antagonist) if they have not undergone orchiectomy
  • White blood cells >= 1.5 x 10^9/L (obtained within 14 days prior to treatment start)
  • Platelets (UNVPLT) >= 100 x 10^9/L (obtained within 14 days prior to treatment start)
  • Hemoglobin (HGB) >= 9 g/dL (obtained within 14 days prior to treatment start)
  • Potassium (K), total calcium (CA) (corrected for serum albumin), magnesium, sodium (NA) and phosphorus within normal limits for the institution or corrected to within normal limits with supplements before first dose of study medication (obtained within 14 days prior to treatment start)
  • International normalized ratio (INR) =< 1.5 (obtained within 14 days prior to treatment start)
  • Serum creatinine (CREAT) =< 1.5 mg/dL or creatinine clearance > 50 mL/min (obtained within 14 days prior to treatment start)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN. If the patient has liver metastases, ALT and AST must still be =< 2.5 x ULN. Patients with liver metastases and AST/ALT above this limit will not be enrolled (obtained within 14 days prior to treatment start)
  • Total serum bilirubin =< 1.5 x ULN; or total bilirubin (TBILI) =< 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert?s syndrome (obtained within 14 days prior to treatment start)
  • Ability to swallow and retain oral medication (without crushing, dissolving or chewing tablets)
  • Phase Ib only: Prior enzalutamide treatment and/or other approved treatments for CRPC are acceptable
  • Phase II only: Participants MUST be treatment na?ve in the CRPC setting: i.e., no prior exposure to abiraterone acetate other specific CYP-17 inhibitors; no prior exposure to enzalutamide or investigational androgen receptor (AR) targeted agents; and no prior exposure to chemotherapy and or RAD-223
  • Sexually active males must agree to use a condom during intercourse while taking the study drug and for at least 3 months after stopping study treatment. Sexually active males should not father a child during this period. A condom is required to be used by vasectomized men in order to prevent delivery of the drug via seminal fluid. Should a woman become pregnant or suspect she is pregnant while her partner is participating in this study, she should inform her treating physician immediately
  • Participant or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Who cannot join

  • Phase II only: Prior exposure to abiraterone acetate
  • Phase II only: Prior exposure to hypomethylating agents like azacytidine or decitabine
  • Phase II only: Prior chemotherapy for castration resistant disease. Chemotherapy given in the castration-sensitive setting is permissible if stopped at least 4 weeks prior to treatment start
  • Phase II only: Prior isotope therapy with strontium-89, samarium or radium-223 within 12 weeks of treatment start
  • Participants with known symptomatic brain metastases
  • Participant has a concurrent malignancy or malignancy within 3 years of treatment start, with the exception of adequately treated, basal or squamous cell carcinoma ornon-melanomatous skin cancer
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  • Participant has a known history of human immunodeficiency virus (HIV) infection (testing not mandatory)
  • Participant has clinically significant, uncontrolled heart disease and/or recent events including any of the following:
  • History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 12 months prior to treatment start
  • History of documented congestive heart failure (New York Heart Association functional classification III-IV)
  • On screening 12 lead electrocardiography (ECG), any of the following cardiac parameters: bradycardia (heart rate < 50 at rest), tachycardia (heart rate > 90 at rest), PR interval > 220 msec, QRS interval > 109 msec or, Fridericia's correction formula (QTcF) > 450 msec. Congenital long QT syndrome or family history of long QT syndrome
  • Patient is currently receiving any of the following medications and cannot be discontinued 7 days prior to treatment start:
  • Known strong inducers or inhibitors of CYP3A4/5, including grapefruit, grapefruit hybrids and pummelos, star-fruit and, Seville oranges
  • Medications that have a known risk to prolong the QT interval or induce Torsades de Pointes
  • Herbal preparations/medications, dietary supplements
  • Patient who has received radiotherapy =< 4 weeks prior to start of treatment or limited field radiation for palliation =< 2 weeks prior to treatment start and, who has not recovered to grade 1 or better from related side effects of such therapy (exceptions include alopecia) and/or in whom >= 30% of the bone marrow was irradiated
  • Patients with central nervous system (CNS) involvement
  • Patients with seizure disorder
  • Patient has not recovered from all toxicities related to prior anticancer therapies to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 grade < 1 (exception to this criterion: patients with any grade of alopecia are allowed to enter the study)
  • Participant has any other concurrent severe and/or uncontrolled medical condition that would cause, in the investigator?s judgment, an unacceptable safety risk
  • Unwilling or unable to follow protocol requirements
  • Any condition which in the investigator?s opinion deems the participant an unsuitable candidate to receive study drug

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

Other trials in United States

About this study

Official title: Phase Ib/II Study of Enzalutamide With Decitabine, a DNA Hypomethylating Agent, in Patients With Metastatic Castrate Resistant Prostate Cancer (mCRPC)

This phase I/II trial studies the side effects and best dose of decitabine and how well it works when given together with enzalutamide in treating patients with castration resistant prostate cancer that has spread to other places in the body. Androgen can cause the growth of prostate cancer cells. Drugs, such as enzalutamide, may lessen the amount of androgen made by the body. Decitabine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving decitabine and enzalutamide may work better in treating participants with castration resistant prostate cancer.

Read the detailed description

PRIMARY OBJECTIVES I. To determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of decitabine in combination with enzalutamide in patients with refractory metastatic castrate resistant prostate cancer (mCRPC). (Phase 1b) II. To determine the 12-month progression free survival rate of patients with enzalutamide-naive metastatic castrate resistant prostate cancer (mCRPC) treated with decitabine plus enzalutamide. (Phase 2)

SECONDARY OBJECTIVES:

  1. To determine the safety and tolerability of decitabine in combination with enzalutamide in patients with refractory metastatic castrate resistant prostate cancer (mCRPC). (Phase 1b) II. To determine the overall response rate, overall survival and prostate specific antigen (PSA) changes in enzalutamide-naive mCRPC patients treated with decitabine plus enzalutamide. (Phase 2) III. To determine the safety and tolerability of decitabine in combination with enzalutamide in the study population. (Phase 2)

EXPLORATORY OBJECTIVES:

  1. To determine the relationship between decitabine dose and plasma biomarkers (e.g., levels of HbF, LINE-1 methylation, number of circulating tumor cell's [CTC?s] and, NY-ESO expression in CTC?s). (Phase 1b) II. To explore plasma and tumor immune biomarkers associated with efficacy to the study combination. (Phase 2) III. To determine if treatment emergent neuroendocrine transformation is present as a result of the treatment combination of enzalutamide plus decitabine. (Phase 2) IV. Evaluate changes in stem cell reprogramming factors and deoxyribonucleic acid (DNA)/ribonucleic acid (RNA) markers resulting from the treatment combination. (Phase 2)

OUTLINE: This is a phase Ib, dose-escalation study of decitabine followed by a phase II study.

Participants receive decitabine intravenously (IV) over 1 hour on days 1-5 and enzalutamide orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up every 3 months for 24 months.

Medical subject headings
Prostatic Neoplasms

What participants receive

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

  • DecitabineDrug

    Also called 5-Aza-2'-deoxycytidine, Aza-TdC, Dacogen, Decitabine for Injection

    Given IV

  • EnzalutamideDrug

    Also called ASP9785, MDV3100, Xtandi

    Given PO

Study groups in NCT03709550
Study groupRoleWhat they receive
Treatment (decitabine, enzalutamide)ExperimentalParticipants receive decitabine IV over 1 hour on days 1-5 and enzalutamide PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Decitabine; Drug: Enzalutamide

What is being measured

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

  1. Dose limiting toxicity determined by estimation of maximum tolerated dose assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 (Phase Ib)

    The dose level at which at least 2 out of 6 patients within the same cohort experience dose-limiting toxicity (DLT).

    Measured: Up to 28 days

  2. Incidence of adverse events assessed by NCI CTCAE version 4.03 (Phase Ib)

    Adverse event (AE) summaries will be organized by body system, frequency of occurrence, intensity (i.e., severity grade), and causality or attribution. Subjects who experience an AE more than once will be counted only once. The occurrence with the maximum severity will be used to calculate intensity. AEs deemed serious and those resulting in treatment withdrawal or death will be summarized separately.

    Measured: Up to 28 days after last dose

  3. Recommended phase II dose (Phase Ib)

    Measured: Up to 28 days

  4. Tumor response (Phase II)

    According to prostate specific antigen (PSA) response (longitudinally), Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1, Prostate Cancer Working Group 3 (PCWG3) criteria and, a longitudinal mixed model for repeated measures of tumor burden: follow serial PSAs and follow target lesions on computed tomography scans and bone scans as per PCWG3 criteria.

    Measured: Up to 24 months

  5. Progression-free survival (PFS) (Phase II)

    The Kaplan-Meier product-limit estimator will be used to estimate PFS distributions.

    Measured: At 12 months

Timeline

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

  1. First posted17 Oct 2018
  2. Study start15 Apr 2021 (estimated)
  3. Primary completion15 Apr 2023 (estimated)
  4. Study completion15 Apr 2024 (estimated)

Why it stopped: lack of funding

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03709550
Sponsor's protocol ID
I 51317
Other IDs
NCI-2018-01755, I 51317
Status last verified
Oct 2022
First submitted
12 Oct 2018
Last updated
5 Oct 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Decitabine and Enzalutamide in people with Castration Levels of Testosterone and Castration-Resistant Prostate Carcinoma, run by Roswell Park Cancer Institute 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 22 inclusion and 22 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: withdrawn, as of the sponsor's last update on 5 Oct 2022. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 withdrawn before enrolling participants, so there are no results.

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?

Dose limiting toxicity determined by estimation of maximum tolerated dose assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 (Phase Ib) (time frame: Up to 28 days). The study lists 5 primary outcomes in all. 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 NCT03709550.

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 5 Oct 2022.

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