Trial Title:
Ruxolitinib and Enzalutamide for the Treatment of Metastatic Castration-Resistant Prostate Cancer
NCT ID:
NCT06616155
Condition:
Castration-Resistant Prostate Carcinoma
Metastatic Prostate Adenocarcinoma
Stage IVB Prostate Cancer AJCC v8
Conditions: Official terms:
Prostatic Neoplasms
Janus Kinase Inhibitors
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biopsy
Description:
Undergo tissue biopsy
Arm group label:
Treatment (ruxolitinib, enzalutamide)
Other name:
BIOPSY_TYPE
Other name:
Bx
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Treatment (ruxolitinib, enzalutamide)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Bone Scan
Description:
Undergo bone scan
Arm group label:
Treatment (ruxolitinib, enzalutamide)
Other name:
Bone Scintigraphy
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT
Arm group label:
Treatment (ruxolitinib, enzalutamide)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
Computerized Tomography (CT) scan
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Drug
Intervention name:
Enzalutamide
Description:
Given PO
Arm group label:
Treatment (ruxolitinib, enzalutamide)
Other name:
ASP9785
Other name:
MDV 3100
Other name:
MDV-3100
Other name:
MDV3100
Other name:
Xtandi
Intervention type:
Drug
Intervention name:
Ruxolitinib
Description:
Given PO
Arm group label:
Treatment (ruxolitinib, enzalutamide)
Other name:
INCB 018424
Other name:
INCB-018424
Other name:
INCB-18424
Other name:
INCB18424
Other name:
Oral JAK Inhibitor INCB18424
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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
- 50% 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)
- A male participant must agree to use of contraception during the treatment period
and for at least 90 days after the last dose of study drug. Female partners of male
patients should also use contraception for 90 days after the last dose of study drug
if they are of childbearing potential
- Platelets ≥ 125,000/mm^3 (obtained within 28 days prior to starting study therapy)
(if creatinine clearance [CrCl] is between 30-59, the platelet entry criteria is >
150,000/mm^3)
- Absolute neutrophil count (ANC) ≥ 1500/mm^3 (obtained within 28 days prior to
starting study therapy)
- Hemoglobin ≥ 11 g/dL (obtained within 28 days prior to starting study therapy) No
transfusions within 90 days prior to screening unless performed for acute bleeding
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3 x upper limit of
normal (ULN) (obtained within 28 days prior to starting study therapy) For patients
with known liver metastasis: (ALT) and aspartate aminotransferase (AST) ≤ 5 x ULN
- Bilirubin ≤ 1.5 the upper limit of normal (ULN) OR direct bilirubin ≤ ULN for
participants with total bilirubin levels > 1.5 x ULN. For subjects with known
Gilbert's disease, bilirubin ≤ 3.0 mg/dL (obtained within 28 days prior to starting
study therapy)
- Creatinine clearance (CrCl) ≥ 30 mL/min (obtained within 28 days prior to starting
study therapy) For creatinine clearance estimation, the Cockcroft and Gault equation
should be used
Exclusion Criteria:
- 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
Gender:
Male
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University of Michigan Comprehensive Cancer Center
Address:
City:
Ann Arbor
Zip:
48109
Country:
United States
Contact:
Last name:
Cancer AnswerLine
Phone:
800-865-1125
Email:
CancerAnswerLine@med.umich.edu
Investigator:
Last name:
Zachery R. Reichert
Email:
Principal Investigator
Start date:
December 1, 2024
Completion date:
December 1, 2028
Lead sponsor:
Agency:
University of Michigan Rogel Cancer Center
Agency class:
Other
Collaborator:
Agency:
Incyte Corporation
Agency class:
Industry
Source:
University of Michigan Rogel Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06616155
