Clinical trial NCT02796898: Study of the Efficacy, Safety, and Pharmacokinetics of SM88 in Patients With Prostate Cancer
Official title: A Phase 1b/2, Open-Label, Dose Escalation Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of SM88 in Patients With Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Prostate Cancer
Rising Prostate Specific Antigen (PSA)
Keywords: Prostate Cancer
PSA
Androgen Deprivation Therapy (ADT)
Lead sponsor: Tyme, Inc
Sponsor class: INDUSTRY
First posted: 2016-06-13
Enrollment: 23
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Detailed description: This is an open-label, multi-center, dose-escalating, dose-expansion study of SM88 in patients with prostate cancer. This study includes 2 phases, a dose-escalation phase that includes PK evaluation, and a dose-expansion phase.

During the first stage, at up to 2 institutions, up to 2 cohorts of 1 to 6 patients each will be enrolled.

During the second stage, the dose selected for evaluation from the Phase 1b will be administered for a total of 30 evaluable patients (inclusive of those treated at the same dose during the dose selection phase) for 6 cycles or until unacceptable toxicity, disease progression, or until any of the treatment discontinuation criteria are met.

Eligibility criteria: Inclusion Criteria:

1. Male ≥18 years of age.
2. Histologically or cytologically confirmed prostate cancer (patients with neuroendocrine carcinoma of the prostate are excluded).
3. Documented PSA progression. Pre-enrollment PSA progression will be as defined by the PCWG3 criteria, e.g. 3 values, increasing, each \>7 days apart.
4. ECOG performance status ≤1
5. Life expectancy \>3 months, in the judgment of the investigator.
6. Adequate organ function defined as follows:

   1. 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)
   2. Hepatic: aspartate transaminase (AST)/alanine transaminase (ALT) ≤2.5 x upper limit of normal (ULN); total or conjugated bilirubin ≤1.5 x ULN
   3. Renal: serum creatinine ≤1.5 x ULN or creatinine clearance (CrCl) ≥60 mL/min as calculated by the Cockroft-Gault method
7. Coagulation: International normalized ratio (INR) ≤1.2
8. With or without one prior line of chemotherapy
9. With or without prior or current ADT or hormone based therapy (up to 2 lines total)
10. Cannot tolerate standard chemotherapy, hormone based therapy or ADT, or elects to opt out of standard therapies.
11. 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.
12. 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)
13. Male patients of fertile potential who engage in heterosexual intercourse with female partners of childbearing potential must agree to use highly effective contraception while enrolled in the study and for at least 6 months following the last dose of study drug. Highly effective birth control methods include the following (the patient should choose 2 to be used with their partner):

    1. Oral, injectable, or implanted hormonal contraceptives
    2. Condom with a spermicidal foam, gel, film, cream, or suppository
    3. Occlusive cap (diaphragm or cervical/vault cap) with a spermicidal foam, gel, film, cream, or suppository
    4. Intrauterine device
    5. Intrauterine system (for example, progestin-releasing coil)
    6. Vasectomized male (as determined by the investigator)
14. Able and willing to provide written informed consent to participate in this study

Exclusion Criteria:

1. PSA minimum starting value \<1 ng/mL at trial entry.
2. 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.
3. 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.
4. 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.
5. 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
6. Local therapy such as radiation or surgery within 8 weeks of study baseline.
7. Current use of a prohibited medication (see Section 8.5) or requires any of these medications during treatment phase
8. 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
9. Minor surgical procedures within 7 days of baseline, or not yet recovered from prior surgery
10. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of any of the components of SM88, e.g. cirrhosis
11. Known human immunodeficiency (HIV) virus infection
12. Hepatitis B surface antigen (HBsAg) positive
13. Hepatitis C virus (HCV) antibody positive
14. Have previously been enrolled in this study or any other study investigating SM88
15. History of any drug allergies or significant adverse reactions to any of the components of SM88.
16. Are currently enrolled in, or have discontinued within 30 days of screening, from a clinical trial involving an investigational product or non-approved use of a drug or device.

Primary outcomes:
measure: 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.
timeFrame: Six months
Secondary outcomes:
measure: Single dose pharmacokinetics (PK) of tyrosine based isomer alone and as a component of SM88 in patients with prostate cancer.
timeFrame: Six months
measure: Multi-dose PK of the individual isomers of tyrosine.
timeFrame: Six months
measure: Multi-dose steady state PK of all 4 components of SM88 in patients with prostate cancer.
timeFrame: Six months
measure: Safety and tolerability of SM88 in patients with prostate cancer.
timeFrame: Six months
measure: Anti-cancer activities of SM88 in patients with prostate cancer.
timeFrame: Six Months
measure: Correlation of toxicity and efficacy with cutaneous hyperpigmentation
timeFrame: Six Months
measure: Radiographic progression-free-survival (rPFS)
timeFrame: Six Months
measure: PSA doubling time before, during and after SM88
timeFrame: Six Months
measure: Effect of SM88 on patient-reported outcomes including quality of life (as measured by the EORTC QLQ-30 and EORTC QLQ-PR25) in patients with prostate cancer.
timeFrame: Six Months
measure: Effect of SM88 on performance status in patients with prostate cancer.
timeFrame: Six months
Other outcomes:
measure: Cutaneous hyperpigmentation as a biomarker in the treatment of prostate cancer by SM88.
timeFrame: Six months
measure: Collection of lymphocyte counts as a biomarker for efficacy.
timeFrame: Six months
measure: Stratification of outcome with known risk factors for prostate cancer.
timeFrame: Six months
measure: Duration of time when a subsequent therapy is needed after treatment with SM88.
timeFrame: Six months
Locations:
city: Lawrence
country: United States
facility: AdvanceMed Research
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center- Montefiore Medical Park
state: New York
city: Bronx
country: United States
facility: Eastchester Center for Cancer Care
state: New York
city: Garden City
country: United States
facility: AccuMed Research Associates
state: New York
city: Bala-Cynwyd
country: United States
facility: MidLantic Urology
state: Pennsylvania
Study officials:
affiliation: Chief Medical Officer TYME Inc.
name: Giuseppe Del Priore, MD, MPH
role: STUDY_DIRECTOR
References:
citation: Steve Hoffman, et al. An open-label trial of SMK treatment of advanced metastatic cancer. J Clin Oncol 31, 2013 (suppl; abstr e22095)
citation: 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.
citation: Avi Retter. Non-Hormonal Therapy for Recurrent Non-Metastatic Prostate Cancer. Oncology Times. 40(4):29-31, February 20, 2018.
citation: 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.
citation: 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.