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

NCT03709550 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: I 51317NCI-2018-01755
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Castration Levels of Testosterone; Castration-Resistant Prostate Carcinoma; Metastatic Prostate Carcinoma in the Soft Tissue; Prostate Carcinoma Metastatic in the Bone; PSA Level Greater Than or Equal to Two; PSA Progression; Stage IV Prostate Cancer AJCC v8; Stage IVA Prostate Cancer AJCC v8; Stage IVB Prostate Cancer AJCC v8

Outcome Measures

Primary Outcomes (5)

• 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).

  Up to 28 days

• 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.

  Up to 28 days after last dose

• Recommended phase II dose (Phase Ib)

  Up to 28 days

• 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.

  Up to 24 months

• Progression-free survival (PFS) (Phase II)

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

  At 12 months

Other Outcomes (12)

• HbF measurements assessed by hemoglobin (Hgb) electrophoresis on peripheral blood (Phase II)

  Up to 24 months

• Molecular pharmacodynamics assessed by flow cytometric assessment of DNMT1-protein in peripheral blood (Phase II)

  Up to 24 months

• LINE-1 methylation levels assessed in peripheral blood by pyrosequencing (Phase II)

  Up to 24 months

Study Arms (1)

Treatment (decitabine, enzalutamide)

EXPERIMENTAL

Participants 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.

Drug: Decitabine; Drug: Enzalutamide

Interventions

Decitabine DRUG

Given IV

Also known as: 5-Aza-2'-deoxycytidine, Aza-TdC, Dacogen, Decitabine for Injection, Deoxyazacytidine, Dezocitidine

Treatment (decitabine, enzalutamide)

Enzalutamide DRUG

Given PO

Also known as: ASP9785, MDV3100, Xtandi

Treatment (decitabine, enzalutamide)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Decitabine; Injections; enzalutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Gurkamal Chatta

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2018
• First Posted: October 17, 2018
• Study Start: April 15, 2021
• Primary Completion: April 15, 2023
• Study Completion: April 15, 2024
• Last Updated: October 5, 2022

Record last verified: 2022-10

Locations

US (1)