PTC596 in Patients With Advanced Solid Tumors

Sponsor

PTC Therapeutics (Industry)

Overall Status

Completed

CT.gov ID

NCT02404480

Collaborator

(none)

Enrollment

Locations

Arms

13.2

Actual Duration (Months)

7.8

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Cancer	Drug: PTC596	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

31 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Open-label, first-in-human, safety and pharmacokinetic (PK)Open-label, first-in-human, safety and pharmacokinetic (PK)

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jan 1, 2016

Actual Primary Completion Date :

Feb 6, 2017

Actual Study Completion Date :

Feb 6, 2017

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Dose-limiting toxicities [28 days]
Determine the RP2D based on occurrence of DLTs and/or biological efficacy as determined by biomarker changes.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
2	Duke University	Durham	North Carolina	United States	27708
3	Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
4	Princess Margaret Cancer Centre	Toronto	Ontario	Canada	M4Y2H8

Sponsors and Collaborators

PTC Therapeutics

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

Responsible Party:

PTC Therapeutics

ClinicalTrials.gov Identifier:

NCT02404480

Other Study ID Numbers:

PTC596-ONC-001-AST

First Posted:

Mar 31, 2015

Last Update Posted:

Dec 8, 2017

Last Verified:

Dec 1, 2017

Study Results

No Results Posted as of Dec 8, 2017