PTC596 in Patients With Advanced Solid Tumors

December 6, 2017 updated by: PTC Therapeutics

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

31

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M4Y2H8
        • Princess Margaret Cancer Centre
  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana Farber Cancer Institute
    • North Carolina
      • Durham, North Carolina, United States, 27708
        • Duke University
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 1
PTC 596 administered twice daily- Dose level 0.65mg/kg
Drug: PTC596
PTC 596 will be administered orally twice a day until unmanageable toxicity, disease progression, or withdrawal of consent is noted
Experimental: Cohort 2
PTC 596 administered twice daily-Dose level 1.3mg/kg
Drug: PTC596
PTC 596 will be administered orally twice a day until unmanageable toxicity, disease progression, or withdrawal of consent is noted
Experimental: Cohort 3
PTC 596 administered twice daily-2.6mg/kg
Drug: PTC596
PTC 596 will be administered orally twice a day until unmanageable toxicity, disease progression, or withdrawal of consent is noted
Experimental: Cohort 4
PTC 596 administered twice daily-Dose level 5.2mg/kg
Drug: PTC596
PTC 596 will be administered orally twice a day until unmanageable toxicity, disease progression, or withdrawal of consent is noted
Experimental: Cohort 5
PTC 596 administered twice daily-Dose level 10mg/kg
Drug: PTC596
PTC 596 will be administered orally twice a day until unmanageable toxicity, disease progression, or withdrawal of consent is noted
Experimental: Cohort 6
PTC 596 administered twice daily-Dose level 7mg/kg
Drug: PTC596
PTC 596 will be administered orally twice a day until unmanageable toxicity, disease progression, or withdrawal of consent is noted
Experimental: Cohort 7 (Bio Marker cohort)
PTC 596 administered twice daily-Dose level 5.2mg/kg
Drug: PTC596
PTC 596 will be administered orally twice a day until unmanageable toxicity, disease progression, or withdrawal of consent is noted

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose-limiting toxicities
Time Frame: 28 days
Determine the RP2D based on occurrence of DLTs and/or biological efficacy as determined by biomarker changes.
28 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse effects
Time Frame: 28days
Define and describe the adverse effects of PTC596 in humans when orally administered on a biw schedule.
28days
Time to Maximum Plasma Concentration (T max)
Time Frame: 28days
Evaluate the Time to Maximum Plasma Concentration (T max) of PTC596 in humans.
28days
Antitumor activity
Time Frame: 28days
Describe any preliminary evidence of antitumor activity of PTC596.
28days
Maximum Plasma Concentration (C max)
Time Frame: 28 days
Evaluate the Maximum Plasma Concentration (C max) of PTC596 in humans
28 days
Plasma Concentration at 24 hours
Time Frame: 28days
Evaluate the Plasma Concentration at 24 hours of PTC596 in humans
28days
Area under the plasma concentration-time curve (AUC)
Time Frame: 28 days
Evaluate the area under the plasma concentration-time curve (AUC) of PTC 596 in humans.
28 days
Terminal half-life (t1/2).
Time Frame: 28 days.
Evaluate the terminal half-life (t1/2) of PTC 596 in humans.
28 days.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

PTC Therapeutics

Investigators

  • Study Director: Edward O'Mara, MD, PTC Therapeutics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2016

Primary Completion (Actual)

February 6, 2017

Study Completion (Actual)

February 6, 2017

Study Registration Dates

First Submitted

March 24, 2015

First Submitted That Met QC Criteria

March 26, 2015

First Posted (Estimate)

March 31, 2015

Study Record Updates

Last Update Posted (Actual)

December 8, 2017

Last Update Submitted That Met QC Criteria

December 6, 2017

Last Verified

December 1, 2017

More Information

Terms related to this study

Other Study ID Numbers

  • PTC596-ONC-001-AST

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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