A Phase I/II Study of Ibrutinib in Previously Treated Epidermal Growth Factor Receptor (EGFR) Mutant Non-Small Cell Lung Cancer

NCT02321540 | Completed Phase 1 Results FDA Drug

• 3 other identifiers: 2014-0602NCI-2015-001241R01CA190628
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of Part 1 of this clinical research study is to find the highest dose of (Imbruvica) ibrutinib that can be given to patients with non-small cell lung cancer (NSCLC). The goal of Part 2 of this clinical research study is to learn if the dose of ibrutinib found in Part 1 can help to control the disease. The safety of this drug will also be studied in both parts of the study.

Conditions

Lung Cancer

Keywords

Lung Cancer; Non-small cell lung cancer; NSCLC; Epidermal growth factor receptor mutations; EGFR; Recurrent non-small cell lung cancer; Ibrutinib; PCI-32765; Imbruvica

Outcome Measures

Primary Outcomes (2)

• Number of Participants With at Least One Dose Limiting Toxicity (DLT) Observed During the Dose Escalation to Determine the Maximum Tolerated Dose (MTD)

  Number of DLT observed at dose levels 560 (starting dose) and 840 mg PO daily to determine the MTD using the 3+3 design.

  First cycle of 28 days

• Overall Response Rate in Patients With EGFR Mutations Using RECIST

  Complete response and partial resopnse rate RECIST 1.1 criteria The response was evaluated after two cycles of therapy and every 8 weeks until the first date that recurrent or progressive disease is objectively documented, up to 2 years.

  after two cycles of therapy and every 8 weeks, up to 2 years

Secondary Outcomes (2)

• Overall Survival (OS)

  from start of treatment to time of progression or death, up to 2 years

• Progression-Free Survival (PFS)

  from start of treatment to time progression or death, whichever occurs first, up to 2 years

Study Arms (1)

Ibrutinib

EXPERIMENTAL

Participants in Part 1 receive dose level of Ibrutinib depending on study joined. First group of participants receive lowest dose level of Ibrutinib. Each new group receives a higher dose of Ibrutinib than the group before it, if no intolerable side effects were seen. This continues until highest tolerable dose of Ibrutinib is found. Participants in Part 2 receive Ibrutinib at highest dose that was tolerated in Part 1 or 840 mg daily. Starting level of Ibrutinib: 560 mg by mouth daily in a 28 day cycle.

Drug: Ibrutinib

Interventions

Ibrutinib DRUG

Part 1 Starting level of Ibrutinib: 560 mg by mouth daily in a 28 day cycle. Part 2 Starting level of Ibrutinib: Maximum tolerated dose from Part 1 or 840 mg daily.

Also known as: PCI-32765, Imbruvica

Ibrutinib

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically or cytologically confirmed stage IV non-small cell lung cancer, or recurrent non-small cell lung cancer which is not amenable to curative intent therapy.
• Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors(RECIST) 1.1 criteria
• For EGFR mutant cohort, patients must have: a) Documented EGFR mutation by Clinical Laboratory Improvement Amendments (CLIA)-certified test b) Documented disease progression on treatment with erlotinib, gefitinib, afatinib, or other EGFR-targeted tyrosine kinase inhibitor c) Tissue available from a biopsy or surgical procedure performed after progression on an EGFR targeted tyrosine kinase inhibitor. If tissue is not available, the patient must have biopsy accessible disease and must be willing to undergo a biopsy.
• For HER2 mutant cohort, patients must have: a) Documented EGFR mutation by CLIA-certified test b)Documented disease progression on treatment with erlotinib, gefitinib, afatinib, or other EGFR-targeted tyrosine kinase inhibitor c)Tissue available following progression on most recent systemic therapy. If tissue is not available, the patient must have biopsy accessible disease and must be willing to undergo a biopsy.
• Age \>/=18 years
• Eastern Cooperative Oncology Group (ECOG) performance status \</=2
• Ability to take pills by mouth
• Patients must have normal organ and marrow function as defined: leukocytes \>/= 3,000/mcL; absolute neutrophil count \>/= 1,500/mcL; hemoglobin \>/= 9 g/dL; total bilirubin \</= 1.5 x institutional upper limit of normal (ULN); AST(SGOT)/ALT(SGPT) \</= 2.5 × ULN or \</= 5 x ULN if metastases to the liver; creatinine clearance \>/= 45 mL/min
• Patients with asymptomatic brain metastases are allowed, as long as they are stable and do not require treatment with anticonvulsants or escalating doses of steroids. Maximum daily dose of steroids should be prednisone 20 mg or equivalent. Radiation therapy for brain metastases must be completed at least 14 days prior to treatment on protocol
• The effects of ibrutinib on the developing human fetus are unknown. Women of child-bearing potential and men must agree to use highly effective contraception (if using hormonal birth control must add a second barrier method; abstinence) prior to study entry, for the duration of study participation as well as for at least 1 month after the last dose of ibrutinib. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use highly effective contraception prior to the study, for the duration of study participation and 3 months after completion of ibrutinib administration.
• Ability to understand and the willingness to sign a written informed consent document

You may not qualify if:

• Patients who have received EGFR tyrosine kinase inhibitors within 72 hours of initiation of study treatment, or treatment with other anti-cancer agents within 21 days of study treatment
• Prior treatment with ibrutinib
• Known hypersensitivity to ibrutinib
• Concurrent use of agents that strongly inhibit or induce CYP3A unless use is approved by the medical monitor
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant and nursing women
• Patients with a history of another active malignancy within the past two years, with the exception of non-melanoma cutaneous malignancy, cervical carcinoma in situ, or ductal carcinoma in situ which has been successfully treated with curative intent therapy
• Any gastrointestinal disorder expected to limit absorption of ibrutinib
• Treatment with warfarin or other vitamin K antagonist. Patients with using warfarin who switch to another form of anticoagulation will be eligible
• Patients with persistent and uncontrolled atrial fibrillation.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Pharmacyclics LLC.: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

ibrutinib

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Results Point of Contact

• Title: Dr. John V. Heymach, Chair, Thoracic-Head & Neck Med Onc
• Organization: UT MD Anderson Cancer Center

jheymach@mdanderson.org

(713) 792-6363

Study Officials

• John Heymach, MD, PHD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2014
• First Posted: December 22, 2014
• Study Start: March 31, 2015
• Primary Completion: September 16, 2021
• Study Completion: September 16, 2021
• Last Updated: October 25, 2023
• Results First Posted: October 25, 2023

Record last verified: 2023-09

Locations

US (1)