PTC596 in Patients With Advanced Solid Tumors

Cancer Clinical Trial

Official title:

A Phase 1 Study of PTC596 in Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02404480
• Other study ID #: PTC596-ONC-001-AST
• Status: Completed
• Phase: Phase 1
• First received: March 24, 2015
• Last updated: December 6, 2017
• Start date: January 2016
• Est. completion date: February 6, 2017

Study information

• Verified date: December 2017
• Source: PTC Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase 1, open-label, first-in-human, safety and pharmacokinetic study of PTC596 in patients with advanced cancer.

Description:

This is a Phase 1, open-label, first-in-human, safety and pharmacokinetic (PK) study of PTC596 in patients with advanced cancer. A variation of the traditional 3+3 dose escalation design will be employed.

PTC596 will be administered orally on a twice a week (biw) schedule. Each 4-week period of drug administration will be considered one cycle. The objective of the study will be to determine the recommended Phase 2 dose (RP2D) and to determine preliminary proof of mechanism of action.

Collectively, data from the Good Laboratory Practice (GLP) and non-GLP studies indicate that 40 mg/kg biw is approximately the severely toxic dose in 10% of animals (STD 10). Therefore, the starting dose in this study will be calculated as one-tenth of the human equivalent dose (HED) of 40 mg/kg biw in rats, which is 0.65 mg/kg biw.

In this study, escalating dose levels will be evaluated to determine the RP2D. Three patients will be enrolled at the starting dose level (0.65 mg/kg biw); if 1 of the 3 patients experiences a dose-limiting toxicity (DLT), an additional 3 patients will be enrolled at the same dose level. Thus, 3 to 6 patients will receive the starting dose level of 0.65 mg/kg. Dose escalation will continue until the occurrence of DLT in ≥2/6 patients at a given dose level. Dose escalation will occur in approximately 100% increments until Grade ≥2, first-cycle toxicity is seen in at least 2 patients across all dose levels, after which dose escalation will occur in smaller (50% or 33%) increments.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: February 6, 2017
• Est. primary completion date: February 6, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed solid malignancy that is metastatic or unresectable, for which standard curative measures do not exist, that has progressed on at least one line of standard therapy or for which no standard therapies exists

• Discontinuation of all other therapies (including other investigational drugs, radiotherapy, or chemotherapy) for the treatment of cancer =4 weeks (=6 weeks if nitrosoureas, =12 weeks if radiotherapy) before initiation of study treatment

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Life expectancy of at least 3 months

• A measured or estimated creatinine clearance (CrCl) =60 mL/min/1.73 m2

Exclusion Criteria:

• Prior bone marrow/hematopoietic stem cell transplantation

• History of solid organ, bone marrow, or progenitor cell transplantation

• History of major surgical procedure within 28 days prior to start of study treatment

• Evidence of ongoing systemic bacterial, fungal, or viral infection. Known human immunodeficiency virus (HIV) infection or acquired-immunodeficiency syndrome (AIDS)-related illness

• Any of the following in the past 6 months: myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, congestive heart failure (New York Heart Association Class III or IV), cerebrovascular accident, transient ischemic attack, other arterial thromboembolic event, or pulmonary embolism

Related Conditions & MeSH terms

• Cancer

Intervention

Drug:
• PTC596
PTC 596 will be administered orally twice a day until unmanageable toxicity, disease progression, or withdrawal of consent is noted

Locations

Country	Name	City	State
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Duke University	Durham	North Carolina
United States	Sarah Cannon Research Institute	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
PTC Therapeutics

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (33)

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* Note: There are 33 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-limiting toxicities	Determine the RP2D based on occurrence of DLTs and/or biological efficacy as determined by biomarker changes.	28 days
Secondary	Adverse effects	Define and describe the adverse effects of PTC596 in humans when orally administered on a biw schedule.	28days
Secondary	Time to Maximum Plasma Concentration (T max)	Evaluate the Time to Maximum Plasma Concentration (T max) of PTC596 in humans.	28days
Secondary	Antitumor activity	Describe any preliminary evidence of antitumor activity of PTC596.	28days
Secondary	Maximum Plasma Concentration (C max)	Evaluate the Maximum Plasma Concentration (C max) of PTC596 in humans	28 days
Secondary	Plasma Concentration at 24 hours	Evaluate the Plasma Concentration at 24 hours of PTC596 in humans	28days
Secondary	Area under the plasma concentration-time curve (AUC)	Evaluate the area under the plasma concentration-time curve (AUC) of PTC 596 in humans.	28 days
Secondary	Terminal half-life (t1/2).	Evaluate the terminal half-life (t1/2) of PTC 596 in humans.	28 days.

External Links

•   BMI1 sustains human glioblastoma multiformae stem cell renewal.
•   Brain cancer stem cells
•   Characterization and Chromosomal localization of the human proto-oncogene
•   Dose escalation study design example
•   Exploratory assessment of dose proportionality
•   Human protein atlas
•   Increased polycomb-group oncogene BMI-1expression coorelates with poor prognosis in Hepatocellular carcinoma
•   Phase 1 clinical trials in oncology
•   Stem cell origin of death from cancer phenotypes of human prostate and breat cancer.