Trial of NRX 194204 in Castration- and Taxane-Resistant Prostate Cancer

Study Overview
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Brief Summary
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This study is to evaluate the benefits of investigational drug, NRX 194204 in slowing down/stopping/reversing progression of the castration resistant and taxane resistant prostate cancer.

Detailed Description
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Numerous studies in pre-clinical models and in human clinical trials have clearly established the potential for the use of rexinoids in the treatment and prevention of cancer. NRX 194204, a second generation rexinoid, is a highly potent and specific activator of RXRs (retinoid X receptors). Because NRX 194204 is significantly more selective for the RXRs relative to the RARs (retinoic acid receptors) than a first generation approved drug, it is associated with fewer adverse events in clinical use. This study seeks to investigate NRX 194204 monotherapy in patients with castration- and taxane- resistant prostate cancer.

Official Title
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A Phase II Trial of NRX 194204 in Castration- and Taxane-Resistant Prostate Cancer

Conditions
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Castration Resistant Prostate Cancer

Intervention / Treatment
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* Drug: NRX 194204


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed prostate cancer Documented progression on at least one prior hormone treatment, AND at least one taxane based chemotherapy regimen, or patient's refusal of chemotherapy treatment Male, Age > 18 years ECOG (Eastern Cooperative Oncology Group) performance score of 0-2 Adequate bone marrow, renal and hepatic function Men of childbearing potential must consent to use barrier contraception while on treatment and for 90 days thereafter Exclusion Criteria: Prior treatment with NRX 194204 or bexarotene (Targretin) Presence of parenchymal brain metastases History of prior malignancy within the past 5 years with the exception of curatively treated basal cell or squamous cell carcinoma of the skin or superficial bladder or other stage I or stage II cancer in complete remission for at least 12 months Patients with a history of unstable or newly diagnosed angina pectoris, documented history of current serious arrhythmia or congestive heart failure or myocardial infarction within 6 months of enrollment Known HIV or hepatitis B or C infection Life expectancy < 3 months Patients with any history of thyroid disease, pituitary disease or treatment with thyroid replacement hormone Patients with a history of pancreatitis or at significant risk of developing pancreatitis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NRX 194204<br>This was a single arm open-label study. All patients enrolled received 20 mg of IRX4204 per day orally, for six months, or longer if the patient had disease stabilization and was tolerating the experimental treatment. | Drug: NRX 194204<br>* NRX 194204 is an oblong, soft, gelatin capsule and will be taken once a day<br>* Other names: Rexinoid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Benefit of NRX 194204 in Men With Castration- and Taxane-resistant Metastatic Prostate Cancer | Clinical benefit will be defined as either non-progression at 8 weeks or radiologic and/or PSA response at any time point with no dose limiting toxicity (DLT) or other toxicity requiring termination of treatment. | participants will be followed for the duration of treatment and follow up, which is up to 2.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall Survival [Time Frame: participants will be followed for the duration of treatment and follow up, which is up to 2.5 years] | participants will be followed for the duration of treatment and follow up, which is up to 2.5 years | 
| Time to Disease Progression | Time to Disease Progression was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, version 1.1. Progression was defined as at least a 20% relative increase and an absolute increase of at least 5mm; or appearance of new lesions. | participants were to be followed for the duration of treatment and follow up; for up to 2.5 years from baseline | 
| Number of Grade 3 and Higher Adverse Events Deemed at Least Possibly Related to NRX 194204 | Number of Grade 3 and higher Adverse Events deemed at least possibly related to NRX 194204 | participants will be followed for the duration of treatment and follow up, which is up to 2.5 years | 
| PSA Response Rate | Prostate specific Antigen (PSA) response rate based on 50% reduction from baseline PSA | participants will be followed for the duration of treatment and follow up, which is up to 2.5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HRPC (Hormone refractory prostate cancer), Androgen independent prostate cancer, CRPC (Castration and Taxane Resistant Prostate Cancer)