Adenocarcinoma of the LungPhase 2NCT01935336
Study of Ponatinib in Patients With Lung Cancer Preselected Using Different Candidate Predictive Biomarkers
A Phase 2 study testing Ponatinib in people with Adenocarcinoma of the Lung and Extensive Stage Small Cell Lung Cancer, run by University of Colorado, Denver at 1 site in United States.
Trial summary
This phase II trial studies how well ponatinib hydrochloride works in treating patients with stage III-IV lung cancer. Ponatinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adenocarcinoma of the Lung, Extensive Stage Small Cell Lung Cancer, Limited Stage Small Cell Lung Cancer
- 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
- 171 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Sep 2013to Nov 2017
- 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
- PART A: Patients must have histologically or cytologically confirmed locally advanced (after failure of local therapy) or metastatic lung cancer (any histology, except carcinoid) stage IIIa, IIIb or IV
- PART A: Existing formalin fixed paraffin embedded biopsy of the lung cancer with potentially sufficient material for analysis
- PART A: Non-small cell lung cancer (NSCLC) with adenocarcinoma histology must have been previously tested for both epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements
- PART A: Able (physically and financially) to travel to University of Colorado for clinical trial treatment
- PART B: Patients must have histologically or cytologically confirmed locally advanced (after failure of local therapy) or metastatic lung cancer (any histology, except carcinoid) stage IIIa, IIIb or IV
- PART B: Patients must be proven to meet marker criteria (FGFR1 silver in situ hybridization (SISH) + in situ hybridization (ISH) +, FGFR1 SISH+ ISH negative [-ve], FGFR1 SISH-ve ISH+, FGFR1 SISH-ve ISH-ve [FGFR1 double negative cohort] or ret proto-oncogene [RET] FISH+) prior to enrollment into Part B (treatment); adenocarcinoma patients must be known to not possess either an EGFR mutation or an ALK rearrangement in their tumor (if positive for one, testing for both is not required)
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- PART B: Patients must have measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
- PART B: Patients may have received any number of lines of prior therapy
- PART B: Life expectancy of >= 3 months
- PART B: Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
- PART B: Leukocytes >= 3,000/mcL
- PART B: Absolute neutrophil count >= 1,500/mcL
- PART B: Hemoglobin >= 9 g/dL
- PART B: Platelets >= 100,000/mcL
- PART B: Total bilirubin =< 1.5 x institutional upper limit of normal (ULN), unless due to Gilbert's syndrome
- PART B: Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X ULN
- PART B: Creatinine =< 1.5 X ULN OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- PART B: Serum lipase =< 1.5 X ULN
- PART B: Serum amylase =< 1.5 X ULN
- PART B: Previous treatment related side-effects/adverse events must have resolved to at least grade 1 or, at the discretion of the investigator, select stable grade 2 toxicities (e.g. alopecia or fatigue) may be permissible if unchanging in grade for at least 3 months following discussion with the principal investigator (PI)
- PART B: Patients with central nervous system (CNS) metastases are eligible for enrollment if they have no overt evidence of neurological deficits, and are not requiring anti-epileptics or steroids to control their neurological symptoms; patients with known CNS metastases must have relevant CNS imaging performed approximately coincident with body imaging during response assessments
- PART B: The effects of ponatinib on the developing human fetus are unknown; for this reason women of child-bearing potential must have a negative urine or blood pregnancy test at screening for Part B; women of child-bearing potential and men must also have documented agreement to use adequate contraception (hormonal or barrier method of birth control; abstinence) from the time of screening until 30 days after the end of study treatment; should a woman become pregnant or suspect she is pregnant while she or her partner are participating in this study, they should inform the treating physician immediately
- PART B: Ability to understand and the willingness to sign a written informed consent document
Who cannot join
- PART A: Known EGFR mutation and/or ALK rearrangement in NSCLC with adenocarcinoma histology
- PART B: No previous treatment with a standard or investigational anti-cancer agent within predicted 5 half-lives of the agent; or 28 days whichever is the shorter; if the plasma half-life is not known or the previous therapy was a monoclonal antibody then a 28 day washout period will be considered as the default requirement
- PART B: No previous or current exposure to other FGFR inhibitors in the FGFR-selected cohorts, or RET inhibitors in the RET selected cohorts
- PART B: Prior radiotherapy to proposed target lesions is not permitted unless completed more than 4 weeks prior to treatment within the study and that there has been documented progression at these sites; radiotherapy to non-target lesions is permitted within 2 weeks of study entry provided all acute effects of the radiotherapy have resolved to =< grade 1
- PART B: History of allergic or severe reactions attributed to compounds of similar chemical or biologic composition to ponatinib
- PART B: Ponatinib is a substrate for cytochrome P450, family 3, subfamily A, polypeptide 4/5 (CYP3A4/5), concurrent use with potent CYP3A4/5 inhibitors or inducers should be undertaken with caution
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- PART B: History of clinically significant bleeding disorder
- PART B: History of acute pancreatitis within 1 year of study or history of chronic pancreatitis
- PART B: Uncontrolled hypertriglyceridemia (triglycerides > 450 mg/dL)
- PART B: Uncontrolled intercurrent illness including, but not limited to:
- Ongoing or active infection requiring intravenous antibiotics
- Psychiatric illness/social situations that would limit compliance with study requirements
- Congestive heart failure, unstable angina pectoris, or myocardial infarction within the 3 months prior to enrollment in part B of the study
- History of clinically significant (as determined by the treating medical doctor [MD]) cardiac arrhythmia (atrial or ventricular)
- PART B: Patients who have had major surgery within 28 days prior to entering the study or those who have not recovered from adverse events > grade 1 relating to the surgery
- PART B: Pregnant or breastfeeding women
- PART B: Patients with inability to take oral medications, or, in the investigator's opinion, gastrointestinal conditions or abnormalities likely to influence the absorption of oral medications
- PART B: Concomitant use of medications known to be associated with torsades-de-pointes
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado Cancer Center
Aurora, Colorado, 80045
About this study
Official title: A Phase II Study of Ponatinib in Cohorts of Patients With Lung Cancer Preselected Using Different Candidate Predictive Biomarkers
This phase II trial studies how well ponatinib hydrochloride works in treating patients with stage III-IV lung cancer. Ponatinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Read the detailed description
This study will look at the safety and effectiveness of the investigational drug ponatinib in lung cancer. The investigators hope that ponatinib will work against tumors that have certain biomarkers. Therefore, the study will pre-screen patients for these certain biomarkers before enrolling them into the main treatment study. Different doses of ponatinib may be tested in this study.
- Conditions
- Adenocarcinoma of the Lung, Extensive Stage Small Cell Lung Cancer, Limited Stage Small Cell Lung Cancer, Recurrent Non-small Cell Lung Cancer, Recurrent Small Cell Lung Cancer, Stage IIIA Non-small Cell Lung Cancer
- Being tested
- Ponatinib
- Keywords
- Lung Cancer, Malignancy, Predictive biomarkers
- Medical subject headings
- Adenocarcinoma of Lung, Carcinoma, Non-Small-Cell Lung, Small Cell Lung Carcinoma, Lung Neoplasms, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PonatinibDrug
Also called Iclusig, AP24534, Multitargeted tyrosine kinase inhibitor AP24534
Ponatinib 45mg taken by mouth each day at the same time with or without food
| Study group | Role | What they receive |
|---|---|---|
| Ponatinib | Experimental | Patients receive ponatinib hydrochloride taken by mouth once or twice a day. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: Ponatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Biomarker FGFR1 (ISH/SISH) Score (Part A)
Biomarker prevalence and its 95% (exact) confidence interval (CI) among the screening patients and for different histologies will be reported. Molecular cohorts for ISH and SISH positivity: FGFR1 ISH+/SISH+, FGFR1 ISH+/SISH-, FGFR1 ISH-/SISH+, and FGFR1 ISH-/SISH-
Measured: Baseline
Overlapping Frequency of FGFR1 (ISH/SISH) Biomarkers (Part A)
Overlapping frequency and its 95% CI between biomarkers among the screening patients and for different histologies will also be reported.
Measured: Baseline
Objective Response Rate (ORR) Per RECIST v1.1 (Part B)
Evaluated using Fisher's exact test with a descriptive p-value. Summarized using binomial proportions with 95% exact binomial confidence intervals.
Measured: From date of first dose until date of Disease Progression or death (up to 153 days), whichever occurred first
Secondary outcomes (1)
Incidence of Adverse Events, Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0
Adverse events will be tabulated per participant, per organ, and per visit.
Measured: From date of first dose until date of Disease Progression (up to 153 days). Assessed at Day 1, Day 8, Day 15 of each 28 day cycle)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2013 (estimated)
- Study start24 Sep 2013
- Primary completionJan 2017
- Study completionNov 2017
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 Adenocarcinoma of the LungStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- 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
- 171 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- Ariad Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Ross D Camidge, MD, PhD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01935336
- Sponsor's protocol ID
- 13-2002.cc
- Other IDs
- NCI-2013-01644
- Status last verified
- Jan 2022
- First submitted
- 27 Aug 2013
- Last updated
- 11 Feb 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Ponatinib in Cohorts of Patients With Lung Cancer Preselected Using Different Candidate Predictive Biomarkers
- ClinicalTrials.gov ID
- NCT01935336
- Acronym / sponsor ID
- 13-2002.cc
- Conditions
- Adenocarcinoma of the Lung, Extensive Stage Small Cell Lung Cancer, Limited Stage Small Cell Lung Cancer, Recurrent Non-small Cell Lung Cancer, Recurrent Small Cell Lung Cancer, Stage IIIA Non-small Cell Lung Cancer
- Keywords
- Lung Cancer, Malignancy, Predictive biomarkers
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 171 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- Ariad Pharmaceuticals
- Study start
- 24 Sep 2013 (actual)
- Primary completion
- Jan 2017 (actual)
- Study completion
- Nov 2017 (actual)
- First posted
- 5 Sep 2013 (estimated)
- Results
- Posted 11 Feb 2022
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 stage III-IV lung cancer. Ponatinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed description
This study will look at the safety and effectiveness of the investigational drug ponatinib in lung cancer. The investigators hope that ponatinib will work against tumors that have certain biomarkers. Therefore, the study will pre-screen patients for these certain biomarkers before enrolling them into the main treatment study. Different doses of ponatinib may be tested in this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ponatinib | Experimental | Drug: PonatinibPatients receive ponatinib hydrochloride taken by mouth once or twice a day. 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 (23 listed)
- PART A: Patients must have histologically or cytologically confirmed locally advanced (after failure of local therapy) or metastatic lung cancer (any histology, except carcinoid) stage IIIa, IIIb or IV
- PART A: Existing formalin fixed paraffin embedded biopsy of the lung cancer with potentially sufficient material for analysis
- PART A: Non-small cell lung cancer (NSCLC) with adenocarcinoma histology must have been previously tested for both epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements
- PART A: Able (physically and financially) to travel to University of Colorado for clinical trial treatment
- PART B: Patients must have histologically or cytologically confirmed locally advanced (after failure of local therapy) or metastatic lung cancer (any histology, except carcinoid) stage IIIa, IIIb or IV
Key exclusion criteria (18 listed)
- PART A: Known EGFR mutation and/or ALK rearrangement in NSCLC with adenocarcinoma histology
- PART B: No previous treatment with a standard or investigational anti-cancer agent within predicted 5 half-lives of the agent; or 28 days whichever is the shorter; if the plasma half-life is not known or the previous therapy was a monoclonal antibody then a 28 day washout period will be considered as the default requirement
- PART B: No previous or current exposure to other FGFR inhibitors in the FGFR-selected cohorts, or RET inhibitors in the RET selected cohorts
- PART B: Prior radiotherapy to proposed target lesions is not permitted unless completed more than 4 weeks prior to treatment within the study and that there has been documented progression at these sites; radiotherapy to non-target lesions is permitted within 2 weeks of study entry provided all acute effects of the radiotherapy have resolved to =< grade 1
- PART B: History of allergic or severe reactions attributed to compounds of similar chemical or biologic composition to ponatinib
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: Iclusig, AP24534, Multitargeted tyrosine kinase inhibitor AP24534Ponatinib 45mg taken by mouth each day at the same time with or without food | Drug | Ponatinib |
Primary outcome
Biomarker FGFR1 (ISH/SISH) Score (Part A)
Time frame: Baseline
Biomarker prevalence and its 95% (exact) confidence interval (CI) among the screening patients and for different histologies will be reported. Molecular cohorts for ISH and SISH positivity: FGFR1 ISH+/SISH+, FGFR1 ISH+/SISH-, FGFR1 ISH-/SISH+, and FGFR1 ISH-/SISH-
Overlapping Frequency of FGFR1 (ISH/SISH) Biomarkers (Part A)
Time frame: Baseline
Overlapping frequency and its 95% CI between biomarkers among the screening patients and for different histologies will also be reported.
Objective Response Rate (ORR) Per RECIST v1.1 (Part B)
Time frame: From date of first dose until date of Disease Progression or death (up to 153 days), whichever occurred first
Evaluated using Fisher's exact test with a descriptive p-value. Summarized using binomial proportions with 95% exact binomial confidence intervals.
1 secondary outcome
Incidence of Adverse Events, Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0
Time frame: From date of first dose until date of Disease Progression (up to 153 days). Assessed at Day 1, Day 8, Day 15 of each 28 day cycle)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Ross D Camidge, MD, PhD principal investigator
University of Colorado, Denver
1 site 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 Adenocarcinoma of the Lung and Extensive Stage Small Cell Lung Cancer, run by University of Colorado, Denver at 1 site 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 23 inclusion and 18 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 11 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 11 Feb 2022). 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?
Biomarker FGFR1 (ISH/SISH) Score (Part A) (time frame: Baseline). The study lists 3 primary outcomes in all. 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 11 Feb 2022.