Clinical trial NCT02404480: PTC596 in Patients With Advanced Solid Tumors
Official title: A Phase 1 Study of PTC596 in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
Lead sponsor: PTC Therapeutics
Sponsor class: INDUSTRY
First posted: 2015-03-31
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Open-label, first-in-human, safety and pharmacokinetic (PK)
Primary purpose: TREATMENT

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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Dose-limiting toxicities
timeFrame: 28 days
Secondary outcomes:
measure: Adverse effects
timeFrame: 28days
measure: Time to Maximum Plasma Concentration (T max)
timeFrame: 28days
measure: Antitumor activity
timeFrame: 28days
measure: Maximum Plasma Concentration (C max)
timeFrame: 28 days
measure: Plasma Concentration at 24 hours
timeFrame: 28days
measure: Area under the plasma concentration-time curve (AUC)
timeFrame: 28 days
measure: Terminal half-life (t1/2).
timeFrame: 28 days.
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
Study officials:
affiliation: PTC Therapeutics
name: Edward O'Mara, MD
role: STUDY_DIRECTOR
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