Ponatinib for Patients Whose Advanced Solid Tumor Cancer Has Activating Mutations Involving the Following Genes: FGFR1, FGFR2, FGFR3, FGFR4, RET, KIT.

NCT02272998 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: OSU-14078NCI-2014-01499
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 2

Brief Summary

This phase II trial studies how well ponatinib hydrochloride works in treating patients with cancer that has spread to other parts of the body (metastatic), has failed previous treatment (refractory), and has one of several alterations, or mutations, in its deoxyribonucleic acid (DNA) sequence. Ponatinib hydrochloride may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It is not yet known whether a patient's genetic alterations may affect how well ponatinib hydrochloride works.

Conditions

Malignant Neoplasm

Keywords

FGFR, RET, KIT

Outcome Measures

Primary Outcomes (1)

• Overall Response, Defined as the Number of Patients Who Achieve Any Response According to Disease Type in the First 6 Courses of Treatment

  The proportion of responses for the purposes of the decision rule will be calculated out of all eligible patients who receive any treatment. Assuming the number of responses is binomially distributed, 95% binomial confidence intervals will also be calculated for the estimate of the proportion of responses. Response for tumors was assessed using the RECIST 1.1 criteria (using computed tomography \[CT\] scans), where response was defined as a partial or complete response.

  Up to 6 months

Secondary Outcomes (5)

• Percentage of Participants With Adverse Events, Defined as Adverse Events That Are Classified as Either Possibly, Probably, or Definitely Related to Study Treatment Per National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0

  Up to 30 days after last dose of study drug, up to a total of 6 years

• Tolerability of the Regimen, Assessed by the Number of Patients Who Required Dose Modifications and/or Dose Delays

  Up to 30 days after last dose of study drug

• Overall Survival

  The time from treatment initiation to death, assessed up to 72 months

• Progression Free Survival

  The time from treatment initiation to progression or death, assessed up to 2 years

• Clinical Benefit Rate (CBR)

  6 months

Other Outcomes (1)

• Correlative Gene and Protein Markers

  Up to 3 years (time of progression)

Study Arms (1)

Treatment (ponatinib hydrochloride)

EXPERIMENTAL

Patients receive ponatinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: ponatinib hydrochloride; Other: laboratory biomarker analysis

Interventions

ponatinib hydrochloride DRUG

Given PO

Also known as: AP24534, Iclusig, multitargeted tyrosine kinase inhibitor AP24534

Treatment (ponatinib hydrochloride)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (ponatinib hydrochloride)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically or cytologically confirmed diagnosis of refractory metastatic solid tumor or chronic hematological malignancy who are eligible for investigational drug therapy
• Patients must have tumor suitable for biopsy (as assessed by trained specialists in interventional radiology) and medically fit to undergo a biopsy or surgical procedure OR if patients do not have a tumor suitable for biopsy but have another tissue available for molecular evaluation
• Patients should have activating genomic alterations in FGFR (mutations, fusions or amplifications \[\> 6 copies\]) or activating genomic alterations in KIT, platelet-derived growth factor receptor alpha \[PDGFRα\], ret proto-oncogene \[RET\], ABL proto-oncogene 1, non-receptor tyrosine kinase \[ABL1\] and fms-related tyrosine kinase 3 \[FLT3\] by any validated Clinical Laboratory Improvement Amendments \[CLIA\]-certified molecular testing (fluorescent in situ hybridization \[FISH\], polymerase chain reaction \[PCR\] or sequencing data are acceptable); CLIA validated results from other institutions; diagnostic labs (e.g. foundation medicine) are acceptable; additional types of activating alterations in these genes can be approved by the principal investigator (PI)
• Patients with advanced cancers should have had at least one prior therapy that is considered standard for that disease type
• Patients with solid tumors must have measurable disease (Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1), defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>= 20 mm with conventional techniques or as \>= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 80%)
• Life expectancy of greater than 3 months
• Patients with multiple malignancies remain eligible
• Patients with an inherited cancer syndrome or a medical history suggestive of an inherited cancer syndrome remain eligible
• Patients must have controlled blood pressure with a systolic blood pressure \< 140 mmHg and diastolic \< 90 mmHg; anti-hypertensive medications are permitted
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and through 4 months after the end of treatment; for females of childbearing potential, a negative pregnancy test must be documented prior to randomization
• Absolute neutrophil count \>= 1,500/mcL
• Platelets \>= 75,000/mcL
• Total bilirubin =\< 1.5 x upper limit of normal (ULN), unless due to Gilbert's syndrome (\< 5 if liver involvement with primary tumor)
• Serum lipase and amylase =\< 1.5 x ULN

You may not qualify if:

• Patients with acute hematological malignancies
• Patients who have not received any prior treatment.
• Patients with known ponatinib-resistant gene alterations
• PDGFRA D842V mutation
• cKIT D816V mutation
• FLT3 D835V/Y/H/F or Y842C mutations
• FGFR3 K652E mutation
• Major surgery (e.g. thoracic, abdominal, vascular, neurosurgery) within 28 days prior to initiating therapy
• History of acute pancreatitis within one year of study or history of chronic pancreatitis
• History of alcohol abuse
• Have uncontrolled hypertriglyceridemia (triglycerides \> 450 mg/dL)
• Patients with history of clinically significant bleeding disorder
• Pregnant women are excluded from this study because ponatinib can affect embryo-fetal development. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ponatinib breastfeeding must be discontinued.
• Patients who are incarcerated are not eligible
• Patients with any history of arterial thromboembolic disease; any patient with a history of myocardial infarction (MI), stroke, transient ischemic attack (TIA), unstable angina or peripheral vascular disease will not be eligible

Sponsors & Collaborators

• Sameek Roychowdhury: lead

Study Sites (2)

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Related Links

• The Jamesline

MeSH Terms

Conditions

Neoplasms; Piebaldism

Interventions

ponatinib

Condition Hierarchy (Ancestors)

Albinism; Eye Diseases, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Skin Diseases, Genetic; Hypopigmentation; Pigmentation Disorders; Skin Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Dr. Sameek Roychowdhury
• Organization: The Ohio State University Comprehensive Cancer Center

Sameek.roychowdhury@osumc.edu

614-685-5842

Study Officials

• Sameek Roychowdhury, MD, PhD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 21, 2014
• First Posted: October 23, 2014
• Study Start: February 24, 2015
• Primary Completion: November 17, 2022
• Study Completion: November 17, 2022
• Last Updated: March 24, 2025
• Results First Posted: March 24, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)