GISTPhase 2GISTNCT01874665
A Phase 2 Trial of Ponatinib in Participants With Metastatic and/or Unresectable Gastrointestinal Stromal Tumor
A Phase 2 study testing Ponatinib in people with GIST, run by Ariad Pharmaceuticals at 4 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- GIST
- What is being tested?
- Ponatinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 4 sitesUnited States
- Study dates
- 5 Jun 2013to 31 Jul 2016
- 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
- Male or female participants >=18 years old.
- GIST with failure of prior TKI therapy defined as:
- Histologically confirmed metastatic and/or unresectable GIST after experiencing failure of prior treatment with imatinib, sunitinib, and regorafenib. If prior TKI treatment was neoadjuvant therapy, then relapse must have occurred during the neoadjuvant therapy in order to consider it failed therapy.
- Participants in Cohort A must have evidence of activation mutations in exon 11 of KIT in their tumors. Demonstration of an exon 11 mutation may be based on prior assessment or on evaluation of a tumor sample after enrollment in this study. Participants in Cohort B must have GIST that lacks activating mutations in KIT exon 11, but may have evidence of another activating mutation such as in KIT exon 9 or in PDGFR-α. Participants may be enrolled in the study prior to determination of the appropriate cohort (as long as both cohorts are open for enrollment).
- 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.
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- Adequate hepatic function as defined by the following criteria:
- Total serum bilirubin less than or equal to (<=) 1.5*Upper Limit of Normal (ULN), unless due to Gilbert's syndrome.
- ALT <=2.5*ULN or <=5.0*ULN if liver metastases are present.
- AST <=2.5*ULN or <=5.0*ULN if liver metastases are present.
- Adequate renal function as defined by the following criterion:
- Serum creatinine <1.5*ULN.
- Adequate pancreatic function as defined by the following criterion:
- 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.
Who cannot join
- 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:
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- Any history of myocardial infarction (MI).
- Any history of unstable angina.
- Congestive heart failure within 6 months prior to enrollment, or left ventricular ejection fraction (LVEF) less than lower limit of normal per local institutional standards within 6 months prior to enrollment.
- History of clinically significant (as determined by the treating physician) atrial arrhythmia.
- Any history of ventricular arrhythmia.
- Any history of cerebrovascular accident or transient ischemic attack (TIA).
- Any history of peripheral vascular infarction, including visceral infarction; or any revascularization procedure of any vasculature, including the placement of a stent.
- Venous thromboembolism including deep venous thrombosis (DVT) or pulmonary embolism within 6 months prior to enrollment.
- 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.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Massachusetts General Hospital, Site #047
Boston, Massachusetts, 02114
Dana-Farber Cancer Institute, Site #008
Boston, Massachusetts, 02215
Fox Chase Cancer Center, Site #012
Philadelphia, Pennsylvania, 19111
Oregon Health & Sciences University, Site #048
Portland, Oregon, 97239
About this study
Official title: Phase 2 Trial of Ponatinib in Patients With Metastatic and/or Unresectable Gastrointestinal Stromal Tumor Following Failure of Prior Tyrosine Kinase Inhibitor Therapy
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.
Read the detailed 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.
- Conditions
- GIST
- Being tested
- Ponatinib
- Keywords
- Gastrointestinal Neoplasms, Gastrointestinal stromal tumor, mesenchymal tumor
- Medical subject headings
- Gastrointestinal Neoplasms, Gastrointestinal Stromal Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PonatinibDrug
Also called AP24534, Iclusig
Ponatinib 45 mg, tablets, orally, once-daily.
| Study group | Role | What they receive |
|---|---|---|
| Cohort A | Experimental | Participants with KIT exon 11-mutant GIST. Receives: Drug: Ponatinib |
| Cohort B | Experimental | Participants with GIST that lack KIT exon 11 mutations (Cohort B). Receives: Drug: Ponatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Benefit Rate (CBR) in Cohort A
To assess clinical benefit rate in participants with KIT exon 11-mutant GIST.It is defined as the composite of complete response(CR),partial response(PR),and stable disease(SD) lasting >=16 weeks per modified Response Evaluation Criteria In Solid Tumors(RECIST) 1.1 as a measure of disease control.CR is complete disappearance of all target lesions and non-target disease, with the exception of nodal disease.All nodes, both target and non-target, must decrease to normal (short axis <10millimeter [mm]).No new lesions.PR is >=30% decrease under baseline of the sum of diameters of all target lesions.The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions.No unequivocal progression of non-target disease.No new lesions.SD is not qualifying for CR,PR,Progressive Disease(PD).PD is >=20% increase from the smallest prior sum of the longest diameter(SLD)and with >=5mm absolute increase, or appearance of a new lesion.
Measured: 16 weeks after first dose
Secondary outcomes (11)
Clinical Benefit Rate (CBR) in Cohort B
To assess clinical benefit rate in participants with GIST that lacks KIT exon 11 mutations (Cohort B) and in the total participant population. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 millimeter [mm]). No new lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. SD was defined as not qualifying for CR, PR, PD.
Measured: 16 weeks after first dose
Progression-free Survival (PFS)
PFS is defined as the duration of time from start of study drug administration to time of objective disease progression or death due to any cause, whichever may come first. To assess PFS in each cohort and in the total participant population.
Measured: From date of enrollment until the end of the study or disease progression or death due to any cause, whichever came first, assessed up to 3 years
Percentage of Participants With Objective Response Rate (ORR)
ORR is defined as the composite of CR and PR per Response Evaluation Criteria in RECIST 1.1, assessed for each cohort and in the total participant population. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). No new lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions.
Measured: From date of enrollment until discontinuation or the end of the study, whichever came first, assessed up to 3 years
Overall Survival (OS)
OS is defined as the time interval between the first dose of study drug to death due to any cause. Overall survival was analyzed using the Kaplan-Meier method.
Measured: From first dose of drug until the end of the study or death, whichever came first, assessed up to 3 years
Number of Participants With Physical Examination
Measured: From date of enrollment until the End-of-Treatment, assessed up to 3 years
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Sign Measurements
Measured: From date of enrollment until the End-of-Treatment, assessed up to 3 years
Number of Participants With Worst Shift From Baseline Values to Post-baseline Values in Laboratory Parameters
Measured: From date of enrollment until the End-of-Treatment, assessed up to 3 years
Number of Participants With TEAEs Related to Electrocardiogram (ECG) Findings
Measured: From date of enrollment until the End-of-Treatment, assessed up to 3 years
Number of Participants With TEAEs Related to Echocardiography Parameter
Measured: From date of enrollment until the End-of-Treatment, assessed up to 3 years
Number of Participants Reporting One or More TEAEs and Serious Adverse Event (SAE)
Measured: From date of enrollment until the End-of-Treatment, assessed up to 3 years
Cmax, SS: Maximum Observed Plasma Concentration at Steady State for Ponatinib
Measured: Pre-dose and at multiple timepoints (up to 1 month) post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2013 (estimated)
- Study start5 Jun 2013
- Primary completion28 Feb 2015
- Study completion31 Jul 2016
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 GISTStudies 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ariad Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01874665
- Sponsor's protocol ID
- AP24534-12-202
- Acronym
- GIST
- Status last verified
- Apr 2018
- First submitted
- 29 May 2013
- Last updated
- 18 May 2018
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Trial of Ponatinib in Patients With Metastatic and/or Unresectable Gastrointestinal Stromal Tumor Following Failure of Prior Tyrosine Kinase Inhibitor Therapy
- ClinicalTrials.gov ID
- NCT01874665
- Acronym / sponsor ID
- GIST / AP24534-12-202
- Conditions
- GIST
- Keywords
- Gastrointestinal Neoplasms, Gastrointestinal stromal tumor, mesenchymal tumor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Ariad PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 5 Jun 2013 (actual)
- Primary completion
- 28 Feb 2015 (actual)
- Study completion
- 31 Jul 2016 (actual)
- First posted
- 11 Jun 2013 (estimated)
- Results
- Posted 17 May 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort A | Experimental | Drug: PonatinibParticipants with KIT exon 11-mutant GIST. |
| Cohort B | Experimental | Drug: PonatinibParticipants with GIST that lack KIT exon 11 mutations (Cohort B). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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:
Key exclusion criteria (24 listed)
- 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])
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 |
|---|---|---|
| PonatinibAlso: AP24534, IclusigPonatinib 45 mg, tablets, orally, once-daily. | Drug | Cohort A, Cohort B |
Primary outcome
Clinical Benefit Rate (CBR) in Cohort A
Time frame: 16 weeks after first dose
To assess clinical benefit rate in participants with KIT exon 11-mutant GIST.It is defined as the composite of complete response(CR),partial response(PR),and stable disease(SD) lasting >=16 weeks per modified Response Evaluation Criteria In Solid Tumors(RECIST) 1.1 as a measure of disease control.CR is complete disappearance of all target lesions and non-target disease, with the exception of nodal disease.All nodes, both target and non-target, must decrease to normal (short axis <10millimeter [mm]).No new lesions.PR is >=30% decrease under baseline of the sum of diameters of all target lesions.The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions.No unequivocal progression of non-target disease.No new lesions.SD is not qualifying for CR,PR,Progressive Disease(PD).PD is >=20% increase from the smallest prior sum of the longest diameter(SLD)and with >=5mm absolute increase, or appearance of a new lesion.
11 secondary outcomes
Clinical Benefit Rate (CBR) in Cohort B
Time frame: 16 weeks after first dose
Progression-free Survival (PFS)
Time frame: From date of enrollment until the end of the study or disease progression or death due to any cause, whichever came first, assessed up to 3 years
Percentage of Participants With Objective Response Rate (ORR)
Time frame: From date of enrollment until discontinuation or the end of the study, whichever came first, assessed up to 3 years
Overall Survival (OS)
Time frame: From first dose of drug until the end of the study or death, whichever came first, assessed up to 3 years
Number of Participants With Physical Examination
Time frame: From date of enrollment until the End-of-Treatment, assessed up to 3 years
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Sign Measurements
Time frame: From date of enrollment until the End-of-Treatment, assessed up to 3 years
Number of Participants With Worst Shift From Baseline Values to Post-baseline Values in Laboratory Parameters
Time frame: From date of enrollment until the End-of-Treatment, assessed up to 3 years
Number of Participants With TEAEs Related to Electrocardiogram (ECG) Findings
Time frame: From date of enrollment until the End-of-Treatment, assessed up to 3 years
Number of Participants With TEAEs Related to Echocardiography Parameter
Time frame: From date of enrollment until the End-of-Treatment, assessed up to 3 years
Number of Participants Reporting One or More TEAEs and Serious Adverse Event (SAE)
Time frame: From date of enrollment until the End-of-Treatment, assessed up to 3 years
Cmax, SS: Maximum Observed Plasma Concentration at Steady State for Ponatinib
Time frame: Pre-dose and at multiple timepoints (up to 1 month) post-dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
The record lists no contact. Use the official record to reach the sponsor.
4 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 in people with GIST, run by Ariad Pharmaceuticals at 4 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 24 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 18 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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 17 May 2016). 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?
Clinical Benefit Rate (CBR) in Cohort A (time frame: 16 weeks after first dose). 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 18 May 2018.