A Phase 1, Open-Label, Dose-Escalation Study Evaluating the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Effects of Orally Administered PWT33597 Mesylate in Subjects With Advanced Malignancies
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Malignancies
- Sponsor
- Pathway Therapeutics, Inc.
- Enrollment
- 22
- Locations
- 4
- Primary Endpoint
- Number of patients with adverse events
- Status
- Completed
- Last Updated
- 13 years ago
Overview
Brief Summary
This is a Phase 1 study evaluating the safety, pharmacokinetics, pharmacodynamics, and clinical effects of orally administered PWT33597 mesylate in subjects with advanced malignancies.
Detailed Description
This is a multicenter, open-label, non-randomized, dose-escalation study, to be conducted in 2 phases. The Dose Escalation Phase (up to 36 patients) will determine the MTD of PWT33597 mesylate and evaluate its safety and tolerability, PK, PD, and preliminary clinical effects; the subsequent Dose Confirmation Phase (up to 36 patients) will be a cohort expansion at or below the MTD of PWT33597 mesylate. Subjects will be treated with once-daily oral doses of PWT33597 in consecutive, 28-day cycles. Subjects will be evaluated regularly for safety. Subjects will return for a follow-up visit 28 days after completion of the last dose of study drug. Subjects who tolerate the drug and who do not experience progressive disease may continue to receive PWT33597 mesylate at the discretion of the principal investigator for up to 24 cycles
Investigators
Eligibility Criteria
Inclusion Criteria
- •Males and females ≥18 years of age.
- •Pathologically confirmed advanced solid tumor or malignant lymphoma for which standard therapy proven to provide clinical benefit does not exist or is no longer effective.
- •Eastern Collaborative Oncology Group (ECOG) Performance Status of ≤1
- •Evaluable disease, either measurable on physical examination or imaging by Response Evaluation Criteria in Solid Tumors (RECIST v1.1), or by the criteria of the International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma, or by informative tumor marker(s).
- •Laboratory values at screening:
- •Absolute neutrophil count ≥1,500 /mm3;
- •Platelets ≥100,000/mm3;
- •Total bilirubin ≤1.5 × the upper limit of normal (ULN);
- •AST (SGOT) ≤2.5 × the ULN;
- •ALT (SGPT) ≤2.5 × the ULN;
Exclusion Criteria
- •Any chemotherapy, immunomodulatory drug therapy, anti-neoplastic hormonal therapy, immunosuppressive therapy, corticosteroids \> 20 mg/day prednisone or equivalent (unless administered to prevent contrast material reactions during radiographic procedures), or growth factor treatment (eg, erythropoietin) within 14 days prior to initiation of study drug.
- •Presence of an acute or chronic toxicity of prior chemotherapy, with the exception of alopecia or peripheral neuropathy, that has not resolved to ≤ Grade 1, as determined by National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) v 4.0
- •Receipt of more than 5 prior regimens of cytotoxic chemotherapy unless prior approval is granted by the sponsor.
- •Radiotherapy within 4 weeks prior to baseline.
- •Receipt of radiotherapy to \>25 % of bone marrow.
- •History of stem cell allotransplantation.
- •Major surgery within 28 days prior to initiation of study drug.
- •Life expectancy \<12 weeks.
- •Active infection requiring systemic therapy.
- •Insulin-requiring diabetes mellitus, or presence of persistent fasting blood glucose \>160 mg/dL.
Outcomes
Primary Outcomes
Number of patients with adverse events
Time Frame: 2 years
Secondary Outcomes
- Number of patients whose tumor show objective response or stable disease by standard criteria(2 years)