Prostate Cancer Clinical Trial

Decitabine/Cedazuridine and Enzalutamide for the Treatment of Metastatic Castrate Resistant Prostate Cancer

Summary

This phase Ib trial is to find out the best dose decitabine/cedazuridine and possible benefits and/or side effects of decitabine/cedazuridine and enzalutamide in treating patients with castrate resistant prostate cancer that has spread to other places in the body (metastatic). Chemotherapy drugs, such as decitabine/cedazuridine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Enzalutamide blocks the use of androgen by the tumor cells. Giving decitabine/cedazuridine together with enzalutamide may reverse or help prevent the acquired therapeutic resistance that is observed when enzalutamide is used alone. Drug resistance occurs when cancer cells stop responding to a chemotherapy that had previously been effective.

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Full Description

PRIMARY OBJECTIVE:

I. To determine the safety of oral decitabine and cedazuridine (decitabine/cedazuridine) in combination with enzalutamide in patients with metastatic castrate resistant prostate cancer (mCRPC).

SECONDARY OBJECTIVE:

I. To determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of oral decitabine/cedazuridine in combination with enzalutamide in patients with metastatic castrate resistant prostate cancer (mCRPC).

OUTLINE: This is a dose-escalation study of decitabine and cedazuridine.

Patients receive decitabine and cedazuridine orally (PO) once daily (QD) on either days 1-3, 1-4, or 1-5 and enzalutamide PO QD on days 1-28. Treatments repeat every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, then every 3 months for 24 months.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

Male >= 18 years of age
Histological or cytological documentation of diagnosis of prostate cancer

Documented progressive metastatic castrate resistant prostate cancer (mCRPC) based on at least one of the following criteria:

Prostate specific antigen (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
Biopsy is preferred where feasible (NOT mandatory) (nodal and visceral disease), particularly in patient at the recommended Phase 2 dose
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 luteinising hormone-releasing factor (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 >= 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)
Creatinine clearance > 50 mL/min (obtained within 14 days prior to treatment start)
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x upper limit of normal (ULN (obtained within 14 days prior to treatment start). 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
Total 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)
Initial dose escalation/de-escalation: Prior enzalutamide treatment and/or other approved treatments for CRPC for the dose finding phase (determination of MTD) of the study is allowed
Expansion cohort: Once the MTD has been determined from the dose escalation/de-escalation portion of the study, patient eligibility for the expansion cohort will be genomically driven and will be restricted to metastatic CRPC patients with detectable genomic alterations in RB1 and/or TP53
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 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
NOTE: For blood chemistry labs, Roswell Park clinical blood chemistries are performed on plasma unless otherwise indicated

Exclusion Criteria:

Participant has a concurrent malignancy or malignancy within 3 years of treatment start, with the exception of adequately treated, basal or squamous cell carcinoma or non-melanomatous skin cancer
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)
Should not have active heart disease: uncompensated CHF; untreated arrhythmia, and no history of MI in the last 12 months

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 5.0 grade <1 (Exception to this criterion: patients with any grade of alopecia are allowed to enter the study)
Unwilling or unable to follow protocol requirements
Participant has any other concurrent severe and/or uncontrolled medical condition that would cause, in the investigator's judgment, an unacceptable safety risk
Any condition which in the Investigator's opinion deems the participant an unsuitable candidate to receive study drug

Study is for people with:

Prostate Cancer

Phase:

Phase 1

Estimated Enrollment:

18

Study ID:

NCT05037500

Recruitment Status:

Recruiting

Sponsor:

Roswell Park Cancer Institute

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There is 1 Location for this study

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Roswell Park Cancer Institute
Buffalo New York, 14263, United States More Info
Gurkamal S. Chatta
Contact
716-845-3117
[email protected]
Gurkamal S. Chatta
Principal Investigator

How clear is this clinincal trial information?

Study is for people with:

Prostate Cancer

Phase:

Phase 1

Estimated Enrollment:

18

Study ID:

NCT05037500

Recruitment Status:

Recruiting

Sponsor:


Roswell Park Cancer Institute

How clear is this clinincal trial information?

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