Status and phase
Conditions
Treatments
About
The purpose of this study is to evaluate the efficacy and safety of ponatinib in participants with metastatic and/or unresectable gastrointestinal stromal tumor (GIST) following failure of prior tyrosine kinase inhibitor (TKI) therapy.
Full description
This is a non-randomized, open label, multi-center phase 2 study to evaluate the efficacy and safety of ponatinib in participants with metastatic and/or unresectable GIST after failure of prior TKI therapy. Participants whose tumors have an activating mutation in exon 11 of cellular KIT (KIT) will be enrolled into Cohort A. Participants whose tumors have other activating mutations will be enrolled into in Cohort B.
The primary objective is to assess clinical benefit in participants with KIT exon 11-mutant GIST (Cohort A) defined as clinical benefit rate (CBR), which is the composite of complete response (CR), partial response (PR) and stable disease (SD) lasting greater than or equal to (>=) 16 weeks per modified response evaluation criteria in solid tumors (RECIST 1.1) as a measure of disease control. The secondary objective is to assess clinical benefit in participants with GIST that lacks an activating KIT exon 11 mutation (Cohort B) and in the total participant population. The efficacy assessments are tumor response using RECIST Version 1.1, modified for GIST and assessment of progression-free survival (PFS) and overall survival (OS). The safety assessments include routine physical and laboratory evaluations, electrocardiograms (ECGs), echocardiograms (ECHOs), and adverse event (AE) monitoring. Other assessments include optional 18F fluorodeoxyglucose positron emission tomography (FDG-PET); optional pre- and post-treatment tumor biopsy for pharmacodynamic studies; and pharmacokinetics (PK). It is estimated that accrual will be complete within 1 year; the total estimated duration of the study is 3 years.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Male or female participants >=18 years old.
GIST with failure of prior TKI therapy defined as:
Measurable disease per modified RECIST 1.1. A lesion in a previously irradiated area is eligible to be considered as measurable disease as long as there is objective evidence of progression of the lesion prior to study enrollment.
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
Adequate hepatic function as defined by the following criteria:
Adequate renal function as defined by the following criterion:
a. Serum creatinine <1.5*ULN.
Adequate pancreatic function as defined by the following criterion:
a. Serum lipase and amylase <=1.5*ULN.
For participants of childbearing potential, a negative pregnancy test must be documented prior to enrollment.
Female and male participants who are fertile must agree to use an effective form of contraception with their sexual partners from signing of the informed consent form for this study through 4 months after the end of treatment.
Provision of written informed consent.
Willingness and ability to comply with scheduled visits and study procedures
Fully recovered (<= Grade 1 or returned to baseline or deemed irreversible) from the acute effects of prior cancer therapy before initiation of study drug.
Exclusion criteria
Major surgery within 28 days prior to initiating therapy
History of bleeding disorder
History of acute pancreatitis within 1 year of study or history of chronic pancreatitis
History of alcohol abuse
Uncontrolled hypertriglyceridemia (triglycerides >450 milligram per deciliter [mg/dL])
Clinically significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to:
Uncontrolled hypertension (diastolic blood pressure greater than (>) 90 millimeter of mercury [mmHg]; systolic >150 mmHg). Participants with hypertension should be under treatment on study entry to effect blood pressure control.
Taking medications with a known risk of Torsades de Pointes.
Taking any medications or herbal supplements that are known to be strong inhibitors of cytochrome P3A4 (CYP3A4) within at least 14 days before the first dose of ponatinib.
Ongoing or active infection. This includes but is not limited to the requirement for intravenous antibiotics.
Known history of human immunodeficiency virus (HIV). Testing is not required in the absence of prior documentation or known history.
Pregnant or breastfeeding.
Malabsorption syndrome or other gastrointestinal illness that could affect oral absorption of study drugs.
Individuals with a history of a different malignancy, other than cervical cancer in situ, basal cell or squamous cell carcinoma of the skin, are ineligible, except if they have been disease-free for at least 5 years, and are deemed by the investigator to be at low risk for recurrence of that malignancy OR if the other primary malignancy is neither currently clinically significant nor requiring active intervention.
Use of any approved TKIs or investigational agents within 2 weeks or 6 half-lives of the agent, whichever is longer, prior to receiving study drug.
Any condition or illness that, in the opinion of the investigator, would compromise participant safety or interfere with the evaluation of the drug.
Primary purpose
Allocation
Interventional model
Masking
45 participants in 2 patient groups
Loading...
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal