Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

All Drugs and Chemicals

Anti-Infective Agents

Antineoplastic Agents

Channel Blockers

Anticonvulsants

Dermatologic Agents

Amino Acids

Androgens

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.

Tyme, Inc

Hormones

Erlotinib Hydrochloride

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Erlotinib (Tarceva)

Daniel Shevrin, MD

The primary objective of this study is to evaluate the effect of erlotinib on the PSA response rate in patients with non-metastatic prostate cancer and a rising PSA on androgen deprivation therapy.

The secondary objectives are to evaluate the effect of erlotinib on the duration of PSA response, to evaluate the effect on the time to PSA progression, to evaluate the toxicity of erlotinib in this patient population, and lastly, to correlate the effect of erlotinib with various epidermal growth factor receptor (EGFR)-related proteins using baseline immunohistochemical (IHC) studies on tissue blocks and peripheral blood mononuclear cells.

Patients with prostate cancer who are treated with surgery or radiation often develop recurrence of their cancer which is manifest only by a rising PSA (Prostate Specific Antigen) level. Many of these patients are treated with hormone therapy. After a fall in the PSA, these patients eventually display evidence of tumor progression clearly demonstrated by another rise in PSA level while receiving hormone therapy. Evaluation for evidence of tumor spread is usually negative. There is currently no effective therapy approved for use in these patients.

The drug erlotinib works by blocking the activity of a protein called Epidermal Growth Factor Receptor (EGFR), which is located on the surface of many prostate cancer cells. Blockage of this protein has been shown to inhibit the growth of prostate tumor cells in a laboratory setting and in animal experiments. Erlotinib has been given to patients with other types of cancers. A recently completed study showed that erlotinib improved the survival of patients with advanced lung cancer who failed standard chemotherapy.

There is currently no effective therapy approved for use in patients with this condition. The purpose of this study is to evaluate the effectiveness and side effects of the drug erlotinib in patients with this condition. Erlotinib is an investigational drug that has not yet been approved by the Federal Drug Administration (FDA) for use in prostate cancer, but has been approved for use in lung cancer.

As previously stated: The primary objective of this study is to evaluate the effect of erlotinib on the PSA response rate in patients with non-metastatic prostate cancer and a rising PSA on androgen deprivation therapy.

Secondary objectives are to evaluate the effect of erlotinib on the duration of PSA response, to evaluate the effect on the time to PSA progression, to evaluate the toxicity of erlotinib in this patient population, and lastly, to correlate the effect of erlotinib with various EGFR-related proteins using baseline immunohistochemical (IHC) studies on tissue blocks and peripheral blood mononuclear cells.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of the Efficacy, Safety, and Pharmacokinetics of SM88 in Patients With Prostate Cancer	NCT02796898	Prostate Cancer Rising Prostate...	SM88 (Cohort 1) SM88 (Cohort 2)	18 Years -	Tyme, Inc
Study of Erlotinib in Patients With Non-Metastatic Prostate Cancer With a Rising Prostate Specific Antigen (PSA) on Hormone Therapy	NCT00148772	Prostate Cancer	Erlotinib (Tarc...	18 Years -	NorthShore University HealthSystem
Study of Erlotinib in Patients With Non-Metastatic Prostate Cancer With a Rising Prostate Specific Antigen (PSA) on Hormone Therapy	NCT00148772	Prostate Cancer	Erlotinib (Tarc...	18 Years -	NorthShore University HealthSystem

Spots Global Cancer Trial Database for rising prostate specific antigen (psa)