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

NCT ID: NCT04296578

Last Updated: 2021-08-12

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-31
• Study Completion Date: 2023-10-31

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.

Detailed Description

PRIMARY OBJECTIVE(S):

· To determine the maximum tolerated dose (MTD) of sodium selenite when given in combination with abiraterone.

SECONDARY OBJECTIVE(S):

• To assess the safety and tolerability of the combination of sodium selenite and abiraterone in subjects with castration resistant prostate cancer (CRPC)
• To assess the pharmacokinetics of sodium selenite
• To assess changes in Prostate specific antigen (PSA) To evaluate the anti tumor activity of sodium selenite and abiraterone when given in combination as determined by biochemical progression free survival (PFS) and radiographic PFS.

Conditions

Prostate Cancer; Castrate Resistant Prostate Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1: 5.5 mg selenite

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

Group Type: EXPERIMENTAL

Abiraterone Acetate

Intervention Type: 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.

Sodium Selenite

Intervention Type: DRUG

11 mg tablets

Prednisone

Intervention Type: DRUG

SOC prednisone 5 mg PO twice daily

Cohort 2: 11 mg selenite

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

Group Type: EXPERIMENTAL

Abiraterone Acetate

Intervention Type: 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.

Sodium Selenite

Intervention Type: DRUG

11 mg tablets

Prednisone

Intervention Type: DRUG

SOC prednisone 5 mg PO twice daily

Cohort 3: 16.5 mg selenite

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

Group Type: EXPERIMENTAL

Abiraterone Acetate

Intervention Type: 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.

Sodium Selenite

Intervention Type: DRUG

11 mg tablets

Prednisone

Intervention Type: DRUG

SOC prednisone 5 mg PO twice daily

Cohort 4: 22 mg selenite

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

Group Type: EXPERIMENTAL

Abiraterone Acetate

Intervention Type: 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.

Sodium Selenite

Intervention Type: DRUG

11 mg tablets

Prednisone

Intervention Type: DRUG

SOC prednisone 5 mg PO twice daily

Cohort 5: 27.5 mg selenite

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

Group Type: EXPERIMENTAL

Abiraterone Acetate

Intervention Type: 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.

Sodium Selenite

Intervention Type: DRUG

11 mg tablets

Prednisone

Intervention Type: DRUG

SOC prednisone 5 mg PO twice daily

Cohort 6: 33 mg selenite

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

Group Type: EXPERIMENTAL

Abiraterone Acetate

Intervention Type: 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.

Sodium Selenite

Intervention Type: DRUG

11 mg tablets

Prednisone

Intervention Type: DRUG

SOC prednisone 5 mg PO twice daily

Interventions

Abiraterone Acetate

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.

Intervention Type: DRUG

Sodium Selenite

11 mg tablets

Intervention Type: DRUG

Prednisone

SOC prednisone 5 mg PO twice daily

Intervention Type: DRUG

Other Intervention Names

Zytiga; Yonsa; CB7630; Sodium selenite pentahydrate; 1, 2-dehydrocortisone; Prednisonum; deltacortisone; deltadehydrocortisone

Eligibility Criteria

Inclusion Criteria

• 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).
• For subjects previously treated with chemotherapy, targeted therapy, immunotherapy, or treatment with an investigational anticancer agent, discontinuation must have occurred ≥ 2 weeks, or after at least 4 half lives, whichever is longer, prior to study drug administration. For enzalutamide and apalutamide, the washout period will be at least 3 weeks prior to start of study drug with no evidence of an anti androgen withdrawal response (ie, no decline in serum PSA within 4 weeks of last dose.)
• For subjects previously treated with other agents approved for the treatment of prostate cancer (5 α reductase inhibitors, estrogens, others), discontinuation of therapy must have occurred ≥ 4 weeks prior to start of study drug. This does not apply to abiraterone.
• Palliative radiotherapy (to bone or soft tissue lesions) must be completed > 2 weeks prior to start of study drug.
• For subjects receiving bone-loss prevention treatment (eg, bisphosphonates or denosumab), the subject must be on stable dose ≥ 4 weeks prior to start of study drug.
• QT interval corrected using Fridericia's method (QTcF) less than 460 msec (see Appendix B for Fridericia's criteria).
• A man who is sexually active with a woman of childbearing potential must agree to use an adequate method of contraception to avoid conception during the study and for 120 days after receiving the last dose of study drug. All men must also not donate sperm during the study and for 120 days after receiving the last dose of study drug.
• Subject must be willing and able to adhere to the prohibitions and restrictions specified in this protocol.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Susan J Knox

Role: PRINCIPAL_INVESTIGATOR

Stanford Universiy

Other Identifiers

PROS0097

Identifier Type: OTHER

Identifier Source: secondary_id

IRB-52111

Identifier Type: -

Identifier Source: org_study_id