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

NCT01935336 | Completed Phase 2 Results DMC

• 2 other identifiers: 13-2002.ccNCI-2013-01644
• Study Type: interventional
• Target: 171
• Locations: 1 country
• Sites: 1

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.

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; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

Keywords

Lung Cancer; Malignancy; Predictive biomarkers

Outcome Measures

Primary Outcomes (3)

• 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-

  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.

  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.

  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

  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)

Study Arms (1)

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.

Drug: Ponatinib

Interventions

Ponatinib DRUG

Ponatinib 45mg taken by mouth each day at the same time with or without food

Also known as: Iclusig, AP24534, Multitargeted tyrosine kinase inhibitor AP24534

Ponatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Ariad Pharmaceuticals: collaborator

Study Sites (1)

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

MeSH Terms

Conditions

Adenocarcinoma of Lung; Carcinoma, Non-Small-Cell Lung; Small Cell Lung Carcinoma; Lung Neoplasms; Neoplasms

Interventions

ponatinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

Due to poor tolerability and safety concerns regarding ponatinib after treating the first few patients, the study did not reach its accrual target (N\~70) for the treatment portion of this study and could not confirm or refute the null hypothesis (needed a minimum of 12 patients treated). This study prescreened a more heterogeneous population. As a result, all four patients that were enrolled onto the ponatinib treatment arm had either squamous or poorly differentiated lung cancer.

Results Point of Contact

• Title: Dr. Ross Camidge
• Organization: U of Colorado, Division of Medical Oncology. Anschutz Medical Campus

ross.camidge@cuanschutz.edu

7208480300

Study Officials

• Ross D Camidge, MD, PhD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2013
• First Posted: September 5, 2013
• Study Start: September 24, 2013
• Primary Completion: January 1, 2017
• Study Completion: November 1, 2017
• Last Updated: February 11, 2022
• Results First Posted: February 11, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)