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Study of Ponatinib in Patients With Lung Cancer Preselected Using Different Candidate Predictive Biomarkers

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ClinicalTrials.gov Identifier: NCT01935336
Recruitment Status : Unknown
Verified November 2019 by University of Colorado, Denver.
Recruitment status was:  Active, not recruiting
First Posted : September 5, 2013
Last Update Posted : November 20, 2019
Sponsor:
Collaborator:
Ariad Pharmaceuticals
Information provided by (Responsible Party):
University of Colorado, Denver

Tracking Information
First Submitted Date  ICMJE August 27, 2013
First Posted Date  ICMJE September 5, 2013
Last Update Posted Date November 20, 2019
Actual Study Start Date  ICMJE May 21, 2014
Actual Primary Completion Date January 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 30, 2013)
  • Prevalence of each biomarker (Part A) [ Time Frame: Up to 5 years ]
    Biomarker prevalence and its 95% (exact) confidence interval (CI) among the screening patients and for different histologies will be reported.
  • Overlapping frequency of biomarkers (Part A) [ Time Frame: Up to 5 years ]
    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: Up to 5 years ]
    Evaluated using Fisher's exact test with a descriptive p-value. Summarized using binomial proportions with 95% exact binomial confidence intervals.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 30, 2013)
Incidence of adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0 [ Time Frame: Up to 5 years ]
The number of adverse events and percentages will be tabulated per organ and per visit.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Ponatinib in Patients With Lung Cancer Preselected Using Different Candidate Predictive Biomarkers
Official Title  ICMJE 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
  • Stage IIIB Non-small Cell Lung Cancer
  • Stage IV Non-small Cell Lung Cancer
Intervention  ICMJE Drug: Ponatinib
Ponatinib 45mg taken by mouth each day at the same time with or without food
Other Names:
  • Iclusig
  • AP24534
  • Multitargeted tyrosine kinase inhibitor AP24534
Study Arms  ICMJE Experimental: Ponatinib
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.
Intervention: Drug: Ponatinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: August 30, 2013)
110
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2020
Actual Primary Completion Date January 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01935336
Other Study ID Numbers  ICMJE 13-2002.cc
NCI-2013-01644 ( Other Identifier: National Cancer Institute )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of Colorado, Denver
Study Sponsor  ICMJE University of Colorado, Denver
Collaborators  ICMJE Ariad Pharmaceuticals
Investigators  ICMJE
Principal Investigator: Ross D Camidge, MD, PhD University of Colorado, Denver
PRS Account University of Colorado, Denver
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP