Brief Title
Study of Ponatinib in Patients With Lung Cancer Preselected Using Different Candidate Predictive Biomarkers
Official Title
A Phase II Study of Ponatinib in Cohorts of Patients With Lung Cancer Preselected Using Different Candidate Predictive Biomarkers
Brief 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.
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 Phase
Phase 2
Study Type
Interventional
Primary Outcome
Prevalence of each biomarker (Part A)
Secondary Outcome
Incidence of adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0
Condition
Adenocarcinoma of the Lung
Intervention
Ponatinib
Study Arms / Comparison Groups
Ponatinib
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
110
Start Date
May 21, 2014
Completion Date
December 2020
Primary Completion Date
January 2017
Eligibility Criteria
Inclusion Criteria:
- 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)
- 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
Exclusion Criteria:
- 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
- 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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Ross D Camidge, MD, PhD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT01935336
Organization ID
13-2002.cc
Secondary IDs
NCI-2013-01644
Responsible Party
Sponsor
Study Sponsor
University of Colorado, Denver
Collaborators
Ariad Pharmaceuticals
Study Sponsor
Ross D Camidge, MD, PhD, Principal Investigator, University of Colorado, Denver
Verification Date
November 2019