Study of the Efficacy, Safety, and Pharmacokinetics of SM88 in Patients With Prostate Cancer

NCT02796898 | Completed Phase 1 DMC

• 1 other identifier: Tyme 2016b
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to evaluate the safety, pharmacokinetics, and efficacy of SM88 in patients with prostate cancer

Conditions

Prostate Cancer; Rising Prostate Specific Antigen (PSA)

Keywords

Prostate Cancer; PSA; Androgen Deprivation Therapy (ADT)

Outcome Measures

Primary Outcomes (1)

• The dose limiting toxicity (DLT), and maximum tolerated dose (MTD) or minimum effective optimum dose of SM88, when 2 dose levels of SM88 are evaluated.

  During 4 days of single dose PK evaluations \[Phase 1b only\], and six 4-week treatment cycles, we will determine if patients in consecutive cohorts experience any dose limiting toxicity to determine MTD, or a complete response with no DLTs observed to determine the optimum dose.

  Six months

Secondary Outcomes (10)

• Single dose pharmacokinetics (PK) of tyrosine based isomer alone and as a component of SM88 in patients with prostate cancer.

  Six months

• Multi-dose PK of the individual isomers of tyrosine.

  Six months

• Multi-dose steady state PK of all 4 components of SM88 in patients with prostate cancer.

  Six months

• Safety and tolerability of SM88 in patients with prostate cancer.

  Six months

• Anti-cancer activities of SM88 in patients with prostate cancer.

  Six Months

Other Outcomes (4)

• Cutaneous hyperpigmentation as a biomarker in the treatment of prostate cancer by SM88.

  Six months

• Collection of lymphocyte counts as a biomarker for efficacy.

  Six months

• Stratification of outcome with known risk factors for prostate cancer.

  Six months

Study Arms (1)

Treated Group

EXPERIMENTAL

SM88 is a combination therapy consisting of 4 agents. One agent, the tyrosine isomer will be increased in each of 2 dose cohorts as follows: Cohort 1: * Tyrosine isomers - 230 mg qd * Phenytoin - 50 mg qd. * Methoxsalen - 10 mg qd * Sirolimus - 0.5 mg qd Cohort 2: Cohort 2 has increasing tyrosine isomer from q.d. to b.i.d. Expansion Cohort: The optimum dose will be expanded in 2nd stage of the study to 30 subjects.

Drug: SM88 (Cohort 1); Drug: SM88 (Cohort 2)

Interventions

SM88 (Cohort 1) DRUG

* Tyrosine Isomers - 230 mg qd * Phenytoin - 50 mg qd. * Methoxsalen - 10 mg qd * Sirolimus - 0.5 mg qd

Also known as: SM88

Treated Group

SM88 (Cohort 2) DRUG

* Tyrosine Isomers - 460 mg (230 mg bid) * Phenytoin - 50 mg qd * Methoxsalen - 10 mg qd * Sirolimus - 0.5 mg qd

Also known as: SM88

Treated Group

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male ≥18 years of age.
• Histologically or cytologically confirmed prostate cancer (patients with neuroendocrine carcinoma of the prostate are excluded).
• Documented PSA progression. Pre-enrollment PSA progression will be as defined by the PCWG3 criteria, e.g. 3 values, increasing, each \>7 days apart.
• ECOG performance status ≤1
• Life expectancy \>3 months, in the judgment of the investigator.
• Adequate organ function defined as follows:
• Hematologic: Platelets ≥100 x 109 /L; Absolute Neutrophil Count (ANC) ≥1.5 x 109/L (without platelet transfusion or growth factors within the 7 days prior to the screening laboratory assessment)
• Hepatic: aspartate transaminase (AST)/alanine transaminase (ALT) ≤2.5 x upper limit of normal (ULN); total or conjugated bilirubin ≤1.5 x ULN
• Renal: serum creatinine ≤1.5 x ULN or creatinine clearance (CrCl) ≥60 mL/min as calculated by the Cockroft-Gault method
• Coagulation: International normalized ratio (INR) ≤1.2
• With or without one prior line of chemotherapy
• With or without prior or current ADT or hormone based therapy (up to 2 lines total)
• Cannot tolerate standard chemotherapy, hormone based therapy or ADT, or elects to opt out of standard therapies.
• Patients who are on ADT prior to the study need not discontinue such therapy during the study, but the use of ADT during the study must be documented.
• All acute toxic effects of any prior antitumor therapy resolved to Grade ≤1 before baseline, with the exception of alopecia (Grade 1 or 2 permitted) and neurotoxicity (Grade 1 or 2 permitted)

You may not qualify if:

• PSA minimum starting value \<1 ng/mL at trial entry.
• Metastatic disease as detected on bone scan, Computed Tomography (CT), Magnetic Resonance Imaging (MRI), or CT-positron emission tomography (PET) beyond the prostate or post-surgical prostate area.
• Any screening laboratory, electrocardiogram (ECG), or other findings that, in the opinion of the investigator or the sponsor, indicate an unacceptable risk for the patient's participation in the study.
• History or evidence of any clinically significant disorder, condition, or disease that, in the opinion of the investigator or medical monitor would pose a risk to the patient's safety or interfere with the study evaluations, procedures, or completion. Examples include intercurrent illness such as active uncontrolled infection, active or chronic bleeding event within 28 days of baseline, uncontrolled cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements.
• History of a concurrent or second malignancy, except for adequately treated local basal cell or squamous cell carcinoma of the skin, superficial bladder cancer, adequately treated Stage 1 or 2 cancer currently in complete remission; or any other cancer that has been in complete remission for ≥5 years
• Local therapy such as radiation or surgery within 8 weeks of study baseline.
• Current use of a prohibited medication (see Section 8.5) or requires any of these medications during treatment phase
• Major surgery, defined as any surgical procedure that involves general anesthesia and a significant incision (i.e., larger than that required for placement of central venous access, percutaneous feeding tube, or biopsy) within 28 days of the first dose of study drug
• Minor surgical procedures within 7 days of baseline, or not yet recovered from prior surgery
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of any of the components of SM88, e.g. cirrhosis
• Known human immunodeficiency (HIV) virus infection
• Hepatitis B surface antigen (HBsAg) positive
• Hepatitis C virus (HCV) antibody positive
• Have previously been enrolled in this study or any other study investigating SM88
• History of any drug allergies or significant adverse reactions to any of the components of SM88.

Sponsors & Collaborators

• Tyme, Inc: lead

Study Sites (5)

AdvanceMed Research

Lawrence, New Jersey, 08648, United States

Location

AccuMed Research Associates

Garden City, New York, 11530-1664, United States

Location

Montefiore Medical Center- Montefiore Medical Park

The Bronx, New York, 10461, United States

Location

Eastchester Center for Cancer Care

The Bronx, New York, 10469, United States

Location

MidLantic Urology

Bala-Cynwyd, Pennsylvania, 19004, United States

Location

Related Publications (5)

• Steve Hoffman, et al. An open-label trial of SMK treatment of advanced metastatic cancer. J Clin Oncol 31, 2013 (suppl; abstr e22095)

  BACKGROUND

• Steve Hoffman, et al. An Open-Label Trial of SMK Treatment of Advanced Metastatic Cancer. 18th World Congress on Controversies in Obstetrics, Gynecology & Infertility (COGI). 473-480, 2014 Monduzzi Editoriale | Proceedings.

  BACKGROUND

• Avi Retter. Non-Hormonal Therapy for Recurrent Non-Metastatic Prostate Cancer. Oncology Times. 40(4):29-31, February 20, 2018.

  BACKGROUND

• Del Priore G, Hoffman S. Timing of androgen-deprivation therapy in prostate cancer. Lancet Oncol. 2017 Nov;18(11):e633. doi: 10.1016/S1470-2045(17)30774-X. Epub 2017 Oct 31. No abstract available.

  PMID: 29208387 BACKGROUND

• Gartrell BA, Roach M 3rd, Retter A, Sokol GH, Del Priore G, Scher HI. Phase II trial of SM-88, a cancer metabolism based therapy, in non-metastatic biochemical recurrent prostate cancer. Invest New Drugs. 2021 Apr;39(2):499-508. doi: 10.1007/s10637-020-00993-4. Epub 2020 Sep 13.

  PMID: 32924093 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

racemetyrosine

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Giuseppe Del Priore, MD, MPH

  Chief Medical Officer TYME Inc.

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: May 30, 2016
• First Posted: June 13, 2016
• Study Start: June 1, 2016
• Primary Completion: May 30, 2019
• Study Completion: May 30, 2019
• Last Updated: July 22, 2019

Record last verified: 2019-07

Locations

US (5)