Castration Resistant Prostate Cancer
Conditions
Keywords
HRPC (Hormone refractory prostate cancer), Androgen independent prostate cancer, CRPC (Castration and Taxane Resistant Prostate Cancer)
Brief summary
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
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.
Interventions
DRUGNRX 194204
NRX 194204 is an oblong, soft, gelatin capsule and will be taken once a day
Sponsors
Io Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Benefit of NRX 194204 in Men With Castration- and Taxane-resistant Metastatic Prostate Cancer | participants will be followed for the duration of treatment and follow up, which is up to 2.5 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | participants will be followed for the duration of treatment and follow up, which is up to 2.5 years | Overall Survival \[Time Frame: participants will be followed for the duration of treatment and follow up, which is up to 2.5 years\] |
| Time to Disease Progression | participants were to be followed for the duration of treatment and follow up; for up to 2.5 years from baseline | 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. |
| 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 | Number of Grade 3 and higher Adverse Events deemed at least possibly related to NRX 194204 |
| PSA Response Rate | participants will be followed for the duration of treatment and follow up, which is up to 2.5 years | Prostate specific Antigen (PSA) response rate based on 50% reduction from baseline PSA |
Countries
United States
Participant flow
Recruitment details
A total of 38 patients were recruited
Participants by arm
| Arm | Count |
|---|---|
| NRX 194204 NRX 194204, 20 mg orally once per day | 38 |
| Total | 38 |
Baseline characteristics
| Characteristic | NRX 194204 |
|---|---|
| Age, Continuous | 71.6 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 38 |
| other Total, other adverse events | 38 / 38 |
| serious Total, serious adverse events | 13 / 38 |
Outcome results
Primary
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.
Time frame: participants will be followed for the duration of treatment and follow up, which is up to 2.5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NRX 194204 | Clinical Benefit of NRX 194204 in Men With Castration- and Taxane-resistant Metastatic Prostate Cancer | 19 Participants |
Secondary
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
Time frame: participants will be followed for the duration of treatment and follow up, which is up to 2.5 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NRX 194204 | Number of Grade 3 and Higher Adverse Events Deemed at Least Possibly Related to NRX 194204 | 23 events |
Secondary
Overall Survival
Overall Survival \[Time Frame: participants will be followed for the duration of treatment and follow up, which is up to 2.5 years\]
Time frame: participants will be followed for the duration of treatment and follow up, which is up to 2.5 years
| Arm | Measure | Value (MEAN) |
|---|---|---|
| NRX 194204 | Overall Survival | 312 days |
Secondary
PSA Response Rate
Prostate specific Antigen (PSA) response rate based on 50% reduction from baseline PSA
Time frame: participants will be followed for the duration of treatment and follow up, which is up to 2.5 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NRX 194204 | PSA Response Rate | stable disease | 6 participants |
| NRX 194204 | PSA Response Rate | progressive disease | 29 participants |
| NRX 194204 | PSA Response Rate | partial response | 1 participants |
Secondary
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.
Time frame: participants were to be followed for the duration of treatment and follow up; for up to 2.5 years from baseline
| Arm | Measure | Value (MEAN) |
|---|---|---|
| NRX 194204 | Time to Disease Progression | 105 days |