Ruxolitinib and Enzalutamide for the Treatment of Metastatic Castration-Resistant Prostate Cancer

NCT06616155 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: UMCC 2023.109NCI-2024-06533HUM00249478
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 3

Brief Summary

This phase I/II tests the safety, side effects and best dose of ruxolitinib in combination with enzalutamide and how well it works in treating patients with prostate cancer that remains despite blocking hormone production (castration-resistant) and that has spread from where it first started to other places in the body (metastatic). Ruxolitinib, a kinase inhibitor, slows down the growth of the tumor by blocking the proteins, JAK1 and JAK2, tumors use to grow. Enzalutamide, an androgen receptor inhibitor, works by blocking the effects of androgen (a male reproductive hormone). This may help stop the growth and spread of tumor cells that need testosterone to grow. Giving ruxolitinib in combination with enzalutamide may be safe, tolerable, and/or effective in treating metastatic castration-resistant prostate cancer.

Conditions

Stage IVB Prostate Cancer AJCC v8; Metastatic Prostate Adenocarcinoma; Castration-Resistant Prostate Carcinoma

Outcome Measures

Primary Outcomes (2)

• Dose-limiting toxicity (DLT)

  DLT will be defined based on the rate of drug-related grade 3-5 adverse events (AEs) experienced. AEs will be assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The proportion of patients at each dose level experiencing each grade level of toxicity will be described. To estimate the frequency and severity of AEs associated with treatment, the proportion of subjects encountering toxicity at each dose level will be reported with exact 95% binomial confidence intervals.

  Up to 28 days

• Maximum tolerated dose (MTD)

  MTD will be defined based on the rate of drug-related grade 3-5 adverse events (AEs) experienced. MTD will be the highest dose level at which the probability of a subject experiencing a DLT during cycle 1 falls between 0.23 and 0.33.

  Up to 28 days

Secondary Outcomes (1)

• Rate of response

  Up to 6 months

Other Outcomes (5)

• Pharmacokinetics (PK) Cmax

  Up to 30 days after last dose of study treatment

• Phosphorylated STAT3 (pSTAT3) percentage

  Up to 30 days after last dose of study treatment

• Objective progression free survival (PFS)

  At start of treatment until clinical progression, death or radiographic progression, assessed up to 2 years

Study Arms (1)

Treatment (ruxolitinib, enzalutamide)

EXPERIMENTAL

Patients receive ruxolitinib PO BID and enzalutamide PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, CT and bone scan throughout the study. Patients may also undergo a tissue biopsy on study.

Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Bone Scan; Procedure: Computed Tomography; Drug: Enzalutamide; Drug: Ruxolitinib

Interventions

Enzalutamide DRUG

Given PO

Also known as: ASP9785, MDV 3100, MDV-3100, MDV3100, Xtandi

Treatment (ruxolitinib, enzalutamide)

Ruxolitinib DRUG

Given PO

Also known as: INCB 018424, INCB-018424, INCB-18424, INCB18424, Oral JAK Inhibitor INCB18424

Treatment (ruxolitinib, enzalutamide)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Treatment (ruxolitinib, enzalutamide)

Biopsy PROCEDURE

Undergo tissue biopsy

Also known as: BIOPSY_TYPE, Bx

Treatment (ruxolitinib, enzalutamide)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (ruxolitinib, enzalutamide)

Bone Scan PROCEDURE

Undergo bone scan

Also known as: Bone Scintigraphy

Treatment (ruxolitinib, enzalutamide)

Eligibility Criteria

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

You may qualify if:

• Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information prior to registration
• Males age ≥ 18 years with progressive metastatic, castration-resistant prostate cancer, previous adenocarcinoma histology confirmation required
• Ability to understand a written informed consent document, as determined by the study physician or designee
• Surgical castration or continuous medical castration ≥ 8 weeks prior to screening; serum testosterone \< 50 ng/dL
• Have progressed on prior abiraterone treatment by Prostate Cancer Working Group 3 prostate specific antigen (PSA) criteria
• PSA must rise on two measurements at least 1 week apart in order to be eligible. Refer to PCWG3 for clarification.
• Most Recent absolute PSA must be \> 2.0 ng/mL
• Patient meets definition of poor responder to abiraterone by one of the following:
• Abiraterone started in hormone-sensitive prostate cancer (HSPC) disease setting (abiraterone started within 4 months of starting continuous androgen deprivation therapy \[ADT\]): \< 12 months duration on abiraterone
• Abiraterone started in castration-resistant prostate cancer (CRPC) disease setting: \< 6 months duration on abiraterone due to progression or failure to achieve PSA50 response while on therapy
• The patient's current or most recent treatment is ADT and abiraterone. Participants must sign consent within 30 days of discontinuing abiraterone or prior to stopping abiraterone
• Patients must be willing to undergo metastatic tumor biopsy during screening. If no metastatic lesion is safely accessible to tumor biopsy, this requirement will not be required
• % of patients must have measurable disease by RECIST 1.1 criteria
• Once 50% of total expected cohort has non-measurable disease, only patients with measurable disease by RECIST 1.1 criteria will be eligible. (Percentages with measurable disease are not relevant within dose escalation. Once dose expansion is started, those at expansion dose would be included in percentage evaluation.)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2 (grade 2 ECOGs should be related to disease and thus potentially reversible)

You may not qualify if:

• History of untreated (with radiotherapy and/or surgery) brain metastasis is not allowed (stable and treated metastases are allowed)
• History of seizures or known hypersensitivity to enzalutamide, ruxolotinib or any of the excipients in the product
• Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with the absorption of the study medications
• Uncontrolled hypertension as indicated by systolic blood pressure (SBP) \> 170 mmHg or diastolic blood pressure (DBP) \> 105 mmHg on 2 consecutive measurements at screening visit unless known to have white coat hypertension syndrome
• Have received chemotherapy in the metastatic castration-resistant setting (docetaxel within the hormone sensitive setting is allowed)
• Failure to recover to grade 1 or lower toxicity related to prior systemic therapy (excluding alopecia and neuropathy) prior to study consent
• Current active infection with any of the following: hepatitis B, hepatitis C, active tuberculosis, latent tuberculosis. Patients with well controlled HIV are eligible however all drug interactions with HIV drug and study therapies have to be reviewed
• History of myocardial infarction, stroke, pulmonary embolism or deep vein thrombosis within 6 months of study enrollment
• Study physician estimates life expectancy less than 6 months or patient is unable to swallow medications
• Patients currently taking fluconazole
• Currently receiving supplements containing androgens or medications known to be strong inhibitors of CYP2C8, strong inducers (except enzalutamide) or strong inhibitors of CYP3A4 and substrates of CYP3A4, CYP2C9 and CYP2C19 with a narrow therapeutic window. If substitution is possible, strong inducers, inhibitors and substrates must be discontinued at least 7 days or 5 half-lives (which ever longer) prior to the first administration of enzalutamide
• Due to risk of tuberculosis (TB) reactivation, patients deemed at high risk by treating provider (e.g., close contact with someone with active TB, history of active/latent TB) should be excluded
• Those with underlying hepatic disease with a CHILD-PUGH class A, B or C impairment are excluded

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead
• Incyte Corporation: collaborator

Study Sites (3)

Rush University

Chicago, Illinois, 60612, United States

NOT YET RECRUITING

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

RECRUITING

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

NOT YET RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Biopsy; Specimen Handling; enzalutamide; ruxolitinib

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)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Zachery R Reichert

  University of Michigan Rogel Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cancer AnswerLine

CONTACT

1-800-865-1125; CancerAnswerLine@med.umich.edu

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: August 31, 2024
• First Posted: September 27, 2024
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2030
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)