Malignant NeoplasmPhase 2NCT02272998
Ponatinib for Patients Whose Advanced Solid Tumor Cancer Has Activating Mutations Involving the Following Genes: FGFR1, FGFR2, FGFR3, FGFR4, RET, KIT.
A Phase 2 study testing ponatinib hydrochloride and laboratory biomarker analysis in people with Malignant Neoplasm, run by Sameek Roychowdhury at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Neoplasm
- What is being tested?
- ponatinib hydrochloride and laboratory biomarker analysis
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 2 sitesUnited States
- Study dates
- 24 Feb 2015to 17 Nov 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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%)
Show all 19Show fewer
- 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
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
- Left ventricular ejection fraction (LVEF) >= institutional lower limit of normal by echocardiogram (ECHO) or multi gated acquisition (MUGA)
- Serum creatinine =< 1.5 mg/dL OR calculated creatinine clearance (Cockcroft-Gault formula) >= 50 mL/min OR 24-hour urine creatinine clearance >= 50 mL/min
- Ability to understand and the willingness to sign a written informed consent document
Who cannot join
- 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
Show all 35Show fewer
- 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
- Patients with history of recurrent venous thromboembolism (deep venous thrombosis or pulmonary embolism) or history of venous thromboembolism within 6 months will not be eligible
- Patients with history of active hepatitis B or C infection or chronic hepatitis with Child Pugh B or C hepatic dysfunction
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to ponatinib
- Patients with prolonged corrected QT interval, defined as QTc >450 msec
- Use of antiplatelet agents other than low-dose aspirin as described
- GI bleed within 30 days prior to registration on study
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to ponatinib.
- Patients with history of atrial arrhythmia (requiring any anti-arrhythmic therapy) or patients with any history of ventricular arrhythmia are excluded
- Clinically significant, uncontrolled intercurrent illness including, but not limited to:
- Symptomatic or active infection
- Uncontrolled hypertension (diastolic blood pressure > 90 mm Hg; systolic > 140 mm Hg); patients with hypertension should be under treatment on study entry to effect blood pressure control
- Psychiatric illness/social situations that would limit compliance with study requirements
- Patients with history of congestive heart failure are excluded
- HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with ponatinib.
- Patients on medications known to be associated with Torsades de Pointes
- Patients who received the last administration of an anti-cancer therapy including, chemotherapy, immunotherapy/biologic therapy, targeted therapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) or within 5 half-lives, whichever is shorter, prior to entering the study.
- Patients taking medications or herbal supplements that are known to be strong cytochrome P450 3A4 (CYP3A4) inhibitors within at least 14 days before the first dose of ponatinib are excluded
- Patients with symptomatic or progressive brain metastases are ineligible; subjects with treated brain metastases are eligible if they have no radiographic or other signs of progression in the brain for >= 4 weeks after completion of local therapy
- Patients with macular edema, retinal vein occlusion or retinal hemorrhage are excluded.
- Patients who have received prior FGFR targeted therapy
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Michigan
Ann Arbor, Michigan, 48109
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
Columbus, Ohio, 43210
About this study
Official title: Phase II Study of Ponatinib for Advanced Cancers With Genomic Alterations in Fibroblastic Growth Factor Receptor (FGFR) and Other Genomic Targets (KIT, PDGFRá, RET FLT3, ABL1)
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.
Read the detailed description
PRIMARY OBJECTIVES:
- To evaluate the response of ponatinib (ponatinib hydrochloride) in patients with fibroblast growth factor receptor (FGFR) altered cancers.
SECONDARY OBJECTIVES:
- To assess the safety and tolerability of ponatinib in advanced solid tumors with genomic FGFR alterations.
II. To assess progression free survival (PFS) and overall survival (OS) with ponatinib.
III. To determine candidate genomic and proteomic biomarkers of sensitivity and resistance to ponatinib using unbiased high throughput approaches (exome, transcriptome, reverse phase protein array [RPPA]).
IV. To assess response of ponatinib in advanced cancers with subsets of genomic FGFR alterations (fusions vs. amplifications vs. mutations).
OUTLINE:
Patients receive ponatinib hydrochloride orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 52 weeks.
- Conditions
- Malignant Neoplasm
- Being tested
- ponatinib hydrochloride, laboratory biomarker analysis
- Keywords
- FGFR, RET, KIT
- Medical subject headings
- Neoplasms, Piebaldism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ponatinib hydrochlorideDrug
Also called AP24534, Iclusig, multitargeted tyrosine kinase inhibitor AP24534
Given PO
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: ponatinib hydrochloride; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Frequency and severity of adverse events will be collected and summarized by descriptive statistics. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns for each of the cohorts as well as across cohorts. In addition, all adverse event data that is graded as 3, 4, or 5 will be reviewed and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing.
Measured: 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
Collected and summarized by descriptive statistics.
Measured: Up to 30 days after last dose of study drug
Overall Survival
Kaplan-Meier curves will be used to estimate the survival distribution.
Measured: The time from treatment initiation to death, assessed up to 72 months
Progression Free Survival
Kaplan-Meier curves will be used to estimate the survival distribution.
Measured: The time from treatment initiation to progression or death, assessed up to 2 years
Clinical Benefit Rate (CBR)
Calculated by the number of patients who have achieve a response and/or are progression-free and alive at 6 months divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for CBR will be calculated.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2014 (estimated)
- Study start24 Feb 2015
- Primary completion17 Nov 2022
- Study completion17 Nov 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Malignant NeoplasmStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sameek Roychowdhury
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Sameek Roychowdhury, Ohio State University Comprehensive Cancer Center
- Investigators
- Sameek Roychowdhury, MD, PhD, Principal investigator, Ohio State University Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02272998
- Sponsor's protocol ID
- OSU-14078
- Other IDs
- NCI-2014-01499
- Status last verified
- Mar 2025
- First submitted
- 21 Oct 2014
- Last updated
- 24 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Ponatinib for Advanced Cancers With Genomic Alterations in Fibroblastic Growth Factor Receptor (FGFR) and Other Genomic Targets (KIT, PDGFRá, RET FLT3, ABL1)
- ClinicalTrials.gov ID
- NCT02272998
- Acronym / sponsor ID
- OSU-14078
- Conditions
- Malignant Neoplasm
- Keywords
- FGFR, RET, KIT
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Sameek RoychowdhuryUniversity, hospital or other
- Study start
- 24 Feb 2015 (actual)
- Primary completion
- 17 Nov 2022 (actual)
- Study completion
- 17 Nov 2022 (actual)
- First posted
- 23 Oct 2014 (estimated)
- Results
- Posted 24 Mar 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVES:
- To evaluate the response of ponatinib (ponatinib hydrochloride) in patients with fibroblast growth factor receptor (FGFR) altered cancers.
SECONDARY OBJECTIVES:
- To assess the safety and tolerability of ponatinib in advanced solid tumors with genomic FGFR alterations.
II. To assess progression free survival (PFS) and overall survival (OS) with ponatinib.
III. To determine candidate genomic and proteomic biomarkers of sensitivity and resistance to ponatinib using unbiased high throughput approaches (exome, transcriptome, reverse phase protein array [RPPA]).
IV. To assess response of ponatinib in advanced cancers with subsets of genomic FGFR alterations (fusions vs. amplifications vs. mutations).
OUTLINE:
Patients receive ponatinib hydrochloride orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 52 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (ponatinib hydrochloride) | Experimental | Drug: ponatinib hydrochloride, Other: laboratory biomarker analysisPatients receive ponatinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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
Key exclusion criteria (35 listed)
- Patients with acute hematological malignancies
- Patients who have not received any prior treatment.
- Patients with known ponatinib-resistant gene alterations
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ponatinib hydrochlorideAlso: AP24534, Iclusig, multitargeted tyrosine kinase inhibitor AP24534Given PO | Drug | Treatment (ponatinib hydrochloride) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (ponatinib hydrochloride) |
Primary outcome
Overall Response, Defined as the Number of Patients Who Achieve Any Response According to Disease Type in the First 6 Courses of Treatment
Time frame: Up to 6 months
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.
5 secondary outcomes
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
Time frame: 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
Time frame: Up to 30 days after last dose of study drug
Overall Survival
Time frame: The time from treatment initiation to death, assessed up to 72 months
Progression Free Survival
Time frame: The time from treatment initiation to progression or death, assessed up to 2 years
Clinical Benefit Rate (CBR)
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- The JameslineLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Malignant Neoplasm
RecruitingPhase 1/2
000860: A Phase I/II Study of Zotiraciclib for Recurrent Malignant Gliomas With Isocitrate Dehydrogenase 1 or 2 (IDH1 or IDH2) Mutations
Brain Tumor, Cancer
Active, not recruiting
A Collaborative Intervention for Improving Cancer Pain Management in Cancer Survivors
Hematopoietic and Lymphoid System Neoplasm, Malignant Solid Neoplasm
Active, not recruitingObservational study
Vaginal Microbiome and HPV Pre-malignant and Cervical Dysplasia
Human Papilloma Virus, Vaginal Flora Imbalance
RecruitingObservational study
Natural History and Biospecimen Acquisition for Children and Adults With Rare Solid Tumors
Malignant Solid Tumors, Other Neoplasms Solid Tumors
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sameek Roychowdhury, MD, PhD principal investigator
Ohio State University Comprehensive Cancer Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ponatinib hydrochloride and laboratory biomarker analysis in people with Malignant Neoplasm, run by Sameek Roychowdhury at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response, Defined as the Number of Patients Who Achieve Any Response According to Disease Type in the First 6 Courses of Treatment (time frame: Up to 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2025.