Study Evaluating Sodium Selenite in Combination With Abiraterone in Castrate Resistant Prostate Cancer Progressing on Abiraterone

NCT04296578 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: IRB-52111PROS0097
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to access the safety of combining sodium selenite with abiraterone and to see what doses of sodium selenite can be safely combined with abiraterone in treating castration resistant prostate cancer.

Conditions

Prostate Cancer; Castrate Resistant Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Dose limiting Toxicity (DLT)

  Adverse events will be assessed according to Common Terminology Criteria for Adverse Events (CTCAE) v5. Dose limiting toxicities (DLTs) of the combination of sodium selenite plus abiraterone are defined as: * Any ≥ Grade 3 non-hematologic toxicity (possibly, probably, or definitely-related adverse event) * Any ≥ Grade 3 thrombocytopenia with bleeding * Any ≥ Grade 4 thrombocytopenia persisting \> 7 days * Any ≥ Grade 4 neutropenia persisting \> 7 days * Treatment withdrawal by participant decision, or for safety reasons as deemed necessary by the investigator The DLT outcome will be reported as the number of DLT events by dose cohort occurring within 2 weeks of the beginning of treatment, a number without dispersion.

  2 weeks

Secondary Outcomes (4)

• Serious Adverse Events (SAEs

  16 weeks

• Sodium Selenite Pharmacokinetics

  1 day

• Blood Levels of Prostate-specific Antigen (PSA)

  upto 12months

• Radiographic Progression free Survival (PFS)

  upto 12months

Study Arms (6)

Cohort 1: 5.5 mg selenite

EXPERIMENTAL

Given orally, 5.5 mg selenite with food (within 30 mins of eating), for 5 weeks and monthly there after

Drug: Abiraterone Acetate; Drug: Sodium Selenite; Drug: Prednisone

Cohort 2: 11 mg selenite

EXPERIMENTAL

Given orally, 11 mg selenite with food (within 30 mins of eating) for 5 weeks and monthly there after

Drug: Abiraterone Acetate; Drug: Sodium Selenite; Drug: Prednisone

Cohort 3: 16.5 mg selenite

EXPERIMENTAL

Given orally, 16.5 mg selenite with food (within 30 mins of eating) for 5 weeks and monthly there after

Drug: Abiraterone Acetate; Drug: Sodium Selenite; Drug: Prednisone

Cohort 4: 22 mg selenite

EXPERIMENTAL

Given orally, 22 mg selenite with food (within 30 mins of eating) for 5 weeks and monthly there after

Drug: Abiraterone Acetate; Drug: Sodium Selenite; Drug: Prednisone

Cohort 5: 27.5 mg selenite

EXPERIMENTAL

Given orally, 27.5 mg selenite with food (within 30 mins of eating) for 5 weeks and monthly there after

Drug: Abiraterone Acetate; Drug: Sodium Selenite; Drug: Prednisone

Cohort 6: 33 mg selenite

EXPERIMENTAL

Given orally, 33 mg selenite with food (within 30 mins of eating) for 5 weeks and monthly there after

Drug: Abiraterone Acetate; Drug: Sodium Selenite; Drug: Prednisone

Interventions

Abiraterone Acetate DRUG

Standard of Care (SOC) abiraterone (Zytiga) as per package insert. The recommended dose of ZYTIGA is 1,000 mg (four 250 mg tablets) administered orally once daily in combination with prednisone 5 mg administered orally twice daily.

Also known as: Zytiga, Yonsa, CB7630

Cohort 1: 5.5 mg selenite; Cohort 2: 11 mg selenite; Cohort 3: 16.5 mg selenite; Cohort 4: 22 mg selenite; Cohort 5: 27.5 mg selenite; Cohort 6: 33 mg selenite

Sodium Selenite DRUG

11 mg tablets

Also known as: Sodium selenite pentahydrate

Cohort 1: 5.5 mg selenite; Cohort 2: 11 mg selenite; Cohort 3: 16.5 mg selenite; Cohort 4: 22 mg selenite; Cohort 5: 27.5 mg selenite; Cohort 6: 33 mg selenite

Prednisone DRUG

SOC prednisone 5 mg PO twice daily

Also known as: 1, 2-dehydrocortisone, Prednisonum, deltacortisone, deltadehydrocortisone

Cohort 1: 5.5 mg selenite; Cohort 2: 11 mg selenite; Cohort 3: 16.5 mg selenite; Cohort 4: 22 mg selenite; Cohort 5: 27.5 mg selenite; Cohort 6: 33 mg selenite

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Each subject must sign an informed consent form (ICF) indicating that he understands the purpose of and procedures required for the study and is willing to participate in the study. Consent is to be obtained prior to the initiation of any study related tests or procedures that are not part of standard of care for the subject's disease.
• Histologically confirmed adenocarcinoma of the prostate with metastatic disease.
• Progression on abiraterone defined by a rise in PSA at 2 time points at least 1 week apart.
• Male ≥18 years of age.
• Prior orchiectomy or serum testosterone levels \< 50 ng/dL determined within 4 weeks prior to start of study drug
• Adequate baseline organ function as defined below:
• Hemoglobin \> 9 with or without transfusion
• Platelets \> 75 with or without transfusion
• Neutrophil: Absolute neutrophil \> 1.0
• T bilirubin \< 1.5 x Upper limit normal (ULN)
• Aspartate aminotransferase (AST)/Alanine Aminotransferase (ALT) \< 2.5 x ULN
• Creatinine \< 1.5 x ULN
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 2 weeks of initiation of study drug administration.
• Ongoing androgen depletion therapy with a gonadotropin releasing hormone (GnRH) analog or inhibitor, or orchiectomy (ie, surgical or medical castration). Note: subjects who have not undergone orchiectomy must continue GnRH analog therapy for the duration of this protocol.
• For subjects previously treated with 1st generation anti androgens (ie, flutamide, nilutamide, or bicalutamide), discontinuation of flutamide or nilutamide therapy must occur \> 4 weeks (\> 6 weeks for bicalutamide) prior to start of study drug with no evidence of an anti androgen withdrawal response (ie, no decline in serum PSA; within 6 weeks of last dose for bicalutamide and 4 weeks of last dose for all other drugs as above).

You may not qualify if:

• Previously documented or current brain metastases.
• Untreated spinal cord compression.
• Known positive test result for human immunodeficiency virus.
• History of clinically significant cardiovascular disease including, but not limited to:
• Myocardial infarction or unstable angina within the 6 months prior to the first dose of study drug.
• Clinically significant cardiac arrhythmia.
• Uncontrolled (persistent) hypertension: systolic blood pressure \> 180 mHg; diastolic blood pressure \>100 mmHg.
• Congestive heart failure (New York Heart Association class III IV).
• Known active or chronic hepatitis B or hepatitis C as demonstrated by hepatitis B surface antigen positivity and/or anti hepatitis C virus positivity, respectively. Subjects with clinically active or chronic liver disease, including liver cirrhosis of Child Pugh class C, are also excluded.
• History of a different malignancy except for the following circumstances: (a) individuals with a history of other malignancies are eligible if they have been disease free for at least 3 years and are deemed by the investigator to be at low risk for recurrence of that malignancy, (b) individuals with a history of treatment for the following cancers are eligible: non muscle invasive bladder cancer, basal cell, or squamous cell carcinoma of the skin and resected melanoma in situ.
• Any serious underlying medical or psychiatric condition (eg, alcohol or drug abuse), dementia or altered mental status or any issue that would impair the ability of the subject to receive or tolerate the planned treatment, to understand informed consent or that in the opinion of the investigator would contraindicate the subject's participation in the study or that would confound the results of the study.
• Evidence of active viral, bacterial, or systemic fungal infection requiring systemic treatment within 7 days prior to the first dose of study drug. Subjects requiring any systemic antiviral, antifungal, or antibacterial therapy for active infection must have completed treatment no less than 7 days prior to the first dose of study drug.
• Enrollment in another therapeutic study.
• Major surgery (eg, requiring general anesthesia) within 3 weeks before screening, or has not fully recovered from prior surgery (ie, unhealed wound), or surgery planned during the time the subject is expected to participate in the study. Note: subjects with planned surgical procedures to be conducted under local anesthesia may participate.

Sponsors & Collaborators

• Stanford University: lead

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Abiraterone Acetate; Sodium Selenite; Prednisone

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)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Selenious Acid; Selenium Compounds; Inorganic Chemicals; Sodium Compounds; Pregnadienediols; Pregnadienes; Pregnanes

Study Officials

• Susan J Knox

  Stanford Universiy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Dose-finding

Study Record Dates

• First Submitted: March 3, 2020
• First Posted: March 5, 2020
• Study Start: October 1, 2020
• Primary Completion: October 1, 2022
• Study Completion: October 1, 2023
• Last Updated: August 12, 2021

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share