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Trial record 2 of 3 for:    SM 88

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

This study is currently recruiting participants.
Verified May 2017 by Tyme, Inc
Sponsor:
ClinicalTrials.gov Identifier:
NCT02796898
First Posted: June 13, 2016
Last Update Posted: September 12, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Tyme, Inc
  Purpose
The purpose of this study is to evaluate the safety, pharmacokinetics, and efficacy of SM88 in patients with prostate cancer

Condition Intervention Phase
Prostate Cancer Rising Prostate Specific Antigen (PSA) Drug: SM88 (Cohort 1) Drug: SM88 (Cohort 2) Phase 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Tyme, Inc:

Primary Outcome Measures:
  • 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. [ Time Frame: Six months ]
    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.


Secondary Outcome Measures:
  • Single dose pharmacokinetics (PK) of tyrosine based isomer alone and as a component of SM88 in patients with prostate cancer. [ Time Frame: Six months ]
    After a single dose of tyrosine based isomer alone on PK Day 1, and a single dose of SM88 on PK Day 3, the plasma concentrations of tyrosine isomers in patients with prostate cancer will be assayed.

  • Multi-dose PK of the individual isomers of tyrosine. [ Time Frame: Six months ]
    The plasma concentrations of tyrosine isomers associated with morning and evening doses of tyrosine isomers on PK Day 1, and also associated with morning and evening doses of SM88, in patients with prostate cancer will be assayed.

  • Multi-dose steady state PK of all 4 components of SM88 in patients with prostate cancer. [ Time Frame: Six months ]
    After approximately 2 weeks of daily dosing of SM88, the plasma concentrations of tyrosine isomers as well as the other 3 drugs of SM88 in patients with prostate cancer will be assayed.

  • Safety and tolerability of SM88 in patients with prostate cancer. [ Time Frame: Six months ]
    Changes from baseline in blood work results and incidence of adverse events associated with treatment of SM88 in patients with prostate cancer.

  • Anti-cancer activities of SM88 in patients with prostate cancer. [ Time Frame: Six Months ]
    Changes from baseline in CTCs, and PSA level per Prostate Cancer Working Group 3 (PCWG3) criteria and radiography per RECIST 1.1 criterial, stratified by circulating tumor cells (CTC) and other blood-based markers including lactate dehydrogenase (LDH), total alkaline phosphatase, bone-specific alkaline phosphatase, urine N-telopeptide, hemoglobin, and neutrophil:lymphocyte ratio (NLR).

  • Correlation of toxicity and efficacy with cutaneous hyperpigmentation [ Time Frame: Six Months ]
    The incident and severity (as assessed by CTCAE v4.0) of treatment-related adverse events and anticancer activities of SM88 are correlated with the degree of cutaneous pigmentation (measured by quantitative image analysis of subject skin color). The total number of subjects with adverse events and efficacy with changes in skin pigmentation during treatment will be reported in aggregate. We will evaluate cutaneous pigmentation as a biomarker in the treatment of prostate cancer by SM88 and stratify pigmentation and known risk factors for outcome analysis.

  • Radiographic progression-free-survival (rPFS) [ Time Frame: Six Months ]
    Duration of survival since treatment initiation with SM88 of study subjects who are without disease progression according to radiology, stratified by PSA level, CTC, and other blood-based markers (including LDH, total alkaline phosphatase, bone-specific alkaline phosphatase, urine N-telopeptide, hemoglobin, and NLR).

  • PSA doubling time before, during and after SM88 [ Time Frame: Six Months ]
    PSA doubling time before, during and after SM88 treatment will be compared to evaluate disease progression rate associated with SM88 treatment.

  • 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. [ Time Frame: Six Months ]
    Changes from baseline in the Quality-of-Life, as measured by EORTC QLQ-30 and QLQ-PR25, stratified by PSA level, CTC, and other blood-based markers (including LDH, total alkaline phosphatase, bone-specific alkaline phosphatase, urine N-telopeptide, hemoglobin, and NLR in patients with prostate cancer).

  • Effect of SM88 on performance status in patients with prostate cancer. [ Time Frame: Six months ]
    Changes from baseline in the performance status (as measured by Eastern Cooperative Oncology Group (ECOG) score) in patients with prostate cancer.


Other Outcome Measures:
  • Cutaneous hyperpigmentation as a biomarker in the treatment of prostate cancer by SM88. [ Time Frame: Six months ]
    Correlation between the anti-cancer activities of SM88 vs. the degree of cutaneous pigmentation (measured by quantitative image analysis of subject skin color). The total number of subjects with efficacy and changes in skin pigmentation during treatment will be reported in aggregate. We will evaluate cutaneous pigmentation as a biomarker for the efficacy of SM88 treatment in patients with prostate cancer.

  • Collection of lymphocyte counts as a biomarker for efficacy. [ Time Frame: Six months ]
    The efficacy of SM88 will be correlated with lymphocyte counts. The total number of subjects with efficacy and lymphocyte counts during treatment will be reported in aggregate. We will evaluate lymphocyte counts as a biomarker for the efficacy of SM88 treatment in patients with prostate cancer.

  • Stratification of outcome with known risk factors for prostate cancer. [ Time Frame: Six months ]
    Stratification of anticancer activities with known risk factors for prostate cancer.

  • Duration of time when a subsequent therapy is needed after treatment with SM88. [ Time Frame: Six months ]
    The duration in time for another therapy due to recurrence of disease.


Estimated Enrollment: 42
Study Start Date: June 2016
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treated Group

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)
  • Tyrosine Isomers - 230 mg qd
  • Phenytoin - 50 mg qd.
  • Methoxsalen - 10 mg qd
  • Sirolimus - 0.5 mg qd
Other Name: SM88
Drug: SM88 (Cohort 2)
  • Tyrosine Isomers - 460 mg (230 mg bid)
  • Phenytoin - 50 mg qd
  • Methoxsalen - 10 mg qd
  • Sirolimus - 0.5 mg qd
Other Name: SM88

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 to 30 patients for 6 cycles or until unacceptable toxicity, disease progression, or until any of the treatment discontinuation criteria are met.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02796898


Contacts
Contact: Avi Kamelhar 718.732.4010 Avi@axellaresearch.com
Contact: Carmen Vicuna 718-732-4078 cvicuna@nycancer.com

Locations
United States, New Jersey
AdvanceMed Research Recruiting
Lawrence, New Jersey, United States, 08648
Contact: Jenna Spatz    609-895-0735    jspatz@advancemed.info   
United States, New York
Dr. Igor Ryndin, MD Active, not recruiting
Brooklyn, New York, United States, 11229
AccuMed Research Associates Recruiting
Garden City, New York, United States, 11530-1664
Contact: Carmen Vicuna    718-732-4078    cvicuna@nycancer.com   
Manhattan Medical Research Recruiting
Manhattan, New York, United States, 10016
Contact: Carmen Vicuna    718-732-4078    cvicuna@nycancer.com   
Eastchester Center for Cancer Care Recruiting
The Bronx, New York, United States, 10469
Contact: Carmen Vicuna    718-732-4078    cvicuna@nycancer.com   
Sponsors and Collaborators
Tyme, Inc
Investigators
Study Director: Giuseppe Del Priore, MD, MPH Chief Medical Officer TYME Inc.
  More Information

Publications:
An open-label trial of SMK treatment of advanced metastatic cancer. Steve Hoffman, Howard Bruckner, Giuseppe Del Priore, et al. Luminant Biosciences, West Caldwell, NJ; Bruckner Oncology, Bronx, NY; Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN; University Diagnostic Medical Imaging, Bronx, NY; University of Varmia and Masuria, Olsztyn, Poland J Clin Oncol 31, 2013 (suppl; abstr e22095)

Responsible Party: Tyme, Inc
ClinicalTrials.gov Identifier: NCT02796898     History of Changes
Other Study ID Numbers: Tyme 2016b
First Submitted: May 30, 2016
First Posted: June 13, 2016
Last Update Posted: September 12, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Tyme, Inc:
Prostate Cancer
PSA
Androgen Deprivation Therapy (ADT)

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Sirolimus
Phenytoin
Methoxsalen
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anticonvulsants
Voltage-Gated Sodium Channel Blockers
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cytochrome P-450 CYP1A2 Inducers
Cytochrome P-450 Enzyme Inducers
Photosensitizing Agents
Dermatologic Agents