Neoplasms

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Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

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Anti-Infective Agents

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Channel Blockers

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Amino Acids

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Sirolimus

Phenytoin

Methoxsalen

Tyrosine

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.

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

SM88 (Cohort 1)

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

SM88 (Cohort 2)

Giuseppe Del Priore, MD, MPH

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

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.

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

A Phase 1b/2, Open-Label, Dose Escalation Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of SM88 in Patients With Prostate Cancer

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.

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 anticancer activities with known risk factors for prostate cancer.

The duration in time for another therapy due to recurrence of disease.

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.

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.

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.

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.

Changes from baseline in blood work results and incidence of adverse events associated with treatment of SM88 in patients with prostate cancer.

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).

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.

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 treatment will be compared to evaluate disease progression rate associated with SM88 treatment.

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).

Changes from baseline in the performance status (as measured by Eastern Cooperative Oncology Group (ECOG) score) in patients with prostate cancer.

Spots Global Cancer Trial Database for sm88 (cohort 2)