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

• Sponsor: Io Therapeutics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01540071
• Collaborator: (none)
• Enrollment: 38
• Location: 1
• Arm: 1
• Duration (Months): 52
• Patients Per Site Per Month: 0.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Castration Resistant Prostate Cancer	Drug: NRX 194204	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 38 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of NRX 194204 in Castration- and Taxane-Resistant Prostate Cancer
• Study Start Date: Aug 1, 2011
• Actual Primary Completion Date: Dec 1, 2015
• Actual Study Completion Date: Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: NRX 194204 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; NRX 194204 is an oblong, soft, gelatin capsule and will be taken once a day; Other Names: Rexinoid

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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]

2. 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.

3. 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

4. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Lalita Pandit, MD	Fountain Valley	California	United States	92708

Sponsors and Collaborators

• Io Therapeutics

Investigators

• Principal Investigator: Lalita Pandit, MD, Lalita Pandit, MD

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Io Therapeutics
• ClinicalTrials.gov Identifier: NCT01540071
• Other Study ID Numbers: 4204-202-2011
• First Posted: Feb 28, 2012
• Last Update Posted: May 14, 2021
• Last Verified: Apr 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Io Therapeutics: HRPC (Hormone refractory prostate cancer); Androgen independent prostate cancer; CRPC (Castration and Taxane Resistant Prostate Cancer)
• Additional relevant MeSH terms: Prostatic Neoplasms

Study Results

Participant Flow

Recruitment Details	A total of 38 patients were recruited

Arm/Group Title	NRX 194204
Arm/Group Description	NRX 194204 capsules, 20 mg PO once per day
Period Title: Overall Study
STARTED	38
COMPLETED	38
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	NRX 194204
Arm/Group Description	NRX 194204, 20 mg orally once per day
Overall Participants	38
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	71.6
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	38 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 10.5%
Not Hispanic or Latino	31 81.6%
Unknown or Not Reported	3 7.9%

Outcome Measures

1. Primary Outcome

Title	Clinical Benefit of NRX 194204 in Men With Castration- and Taxane-resistant Metastatic Prostate Cancer
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NRX 194204
Arm/Group Description	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. NRX 194204: NRX 194204 is an oblong, soft, gelatin capsule and will be taken once a day
Measure Participants	38
Count of Participants [Participants]	19 50%

2. Secondary Outcome

Title	Overall Survival
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NRX 194204
Arm/Group Description	This was a single arm open-label study. All patients enrolled and treated 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.
Measure Participants	38
Mean (Full Range) [days]	312

3. Secondary Outcome

Title	Time to Disease Progression
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NRX 194204
Arm/Group Description	This was a single arm open-label study. All patients enrolled and treated 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.
Measure Participants	36
Mean (Full Range) [days]	105

4. Secondary Outcome

Title	Number of Grade 3 and Higher Adverse Events Deemed at Least Possibly Related to NRX 194204
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NRX 194204
Arm/Group Description	This was a single arm open-label study. All patients enrolled and treated 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.
Measure Participants	38
Number [events]	23

5. Secondary Outcome

Title	PSA Response Rate
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NRX 194204
Arm/Group Description	This was a single arm open-label study. All patients enrolled and treated 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.
Measure Participants	36
partial response	1 2.6%
stable disease	6 15.8%
progressive disease	29 76.3%

Adverse Events

Time Frame	Adverse events were collected as long as each individual patient was receiving study drug, and were further followed for each individual patient for up to a maximum of 2.5 years, or until they were lost to follow-up, or died.
Arm/Group Title	NRX 194204
Arm/Group Description	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. NRX 194204: NRX 194204 is an oblong, soft, gelatin capsule and will be taken once a day
All Cause Mortality
	NRX 194204
	Affected / at Risk (%)	# Events
Total	0/38 (0%)
Serious Adverse Events
	NRX 194204
	Affected / at Risk (%)	# Events
Total	13/38 (34.2%)
Blood and lymphatic system disorders
Elevated PT	1/38 (2.6%)	1
Elevated INR	1/38 (2.6%)	1
Elevated PTT	1/38 (2.6%)	1
Deep Vein Thrombosis	1/38 (2.6%)	1
Anemia	2/38 (5.3%)	2
Cardiac disorders
Congestive Heart Failure	2/38 (5.3%)	2
Gastrointestinal disorders
Probable Upper Gastrointestinal Bleed	1/38 (2.6%)	1
Viral Gastroenteritis	1/38 (2.6%)	1
Infections and infestations
Enterococcus Bacteremia	1/38 (2.6%)	1
Metabolism and nutrition disorders
Dehydration	2/38 (5.3%)	2
Musculoskeletal and connective tissue disorders
Generalized Muscle Weakness	2/38 (5.3%)	2
Nervous system disorders
Confusion	2/38 (5.3%)	2
Hallucinations	1/38 (2.6%)	1
Renal and urinary disorders
Urinary Tract Infection	1/38 (2.6%)	2
Rectal Bleeding	1/38 (2.6%)	1
Respiratory, thoracic and mediastinal disorders
Pleural Effusion	1/38 (2.6%)	1
Dyspnea	2/38 (5.3%)	2
Chest Pain	1/38 (2.6%)	1
Other (Not Including Serious) Adverse Events
	NRX 194204
	Affected / at Risk (%)	# Events
Total	38/38 (100%)
Blood and lymphatic system disorders
Anemia	6/38 (15.8%)	6
Leucocytopenia	6/38 (15.8%)	6
Endocrine disorders
Hypothyroidism	12/38 (31.6%)	12
Gastrointestinal disorders
Vomiting	3/38 (7.9%)	3
Nausea	3/38 (7.9%)	3
Hepatobiliary disorders
Increase Alkaline Phosphatase	2/38 (5.3%)	2
Metabolism and nutrition disorders
Hypertriglyceridemia	15/38 (39.5%)	15
Fatigue	13/38 (34.2%)	13
Anorexia	5/38 (13.2%)	5
Dehydration	2/38 (5.3%)	2
Hypercholesterolemia	5/38 (13.2%)	5
Musculoskeletal and connective tissue disorders
Back Pain	4/38 (10.5%)	4
Renal and urinary disorders
Urinary Tract Infection	2/38 (5.3%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.