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

NCT02321540

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 2014-0602
  • SECONDARY ID: NCI-2015-00124
  • SECONDARY ID: 1R01CA190628
  • NCT ID: NCT02321540

Conditions

  • Lung Cancer

Interventions

DrugSynonymsArms
IbrutinibPCI-32765, ImbruvicaIbrutinib

Purpose

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.

Detailed Description

      Study Groups:

      If you are found to be eligible to take part in this study, you will be assigned to a study
      group based on when you join this study. Up to 4 groups of up to 6 participants will be
      enrolled in Part 1 of the study, and up to19 participants will be enrolled in Part 2.

      If you are enrolled in Part 1, the dose of ibrutinib you receive will depend on when you join
      this study. The first group of participants will receive the lowest dose level of ibrutinib.
      Each new group will receive a higher dose of ibrutinib than the group before it, if no
      intolerable side effects were seen. This will continue until the highest tolerable dose of
      ibrutinib is found.

      If you are enrolled in Part 2, you will receive ibrutinib at the highest dose that was
      tolerated in Part 1.

      Study Drug Administration:

      You will take ibrutinib pills 1 time each day, at about the same time every day. You may take
      your dose of ibrutinib with or without food.

      Study Visits:

      Each cycle is 4 weeks.

      On Day 1 of all cycles:

        -  You will have a physical exam

        -  Blood (about 3 teaspoons) will be drawn for routine tests.

        -  On Cycle 2 only, blood (about 1 teaspoon each time) will be drawn for pharmacokinetic
           (PK) testing before your dose and then 4 more times over the next 6 hours after your
           dose. PK testing measure the amount of study drug in the body at different timepoints.

        -  If you the doctor thinks it is needed, blood (about ½ teaspoon) or urine will be
           collected for pregnancy testing.

      Every 8 weeks, you will have a CT, MRI, or x-ray to check the status of the disease. You will
      have the same type of scan performed as you did at screening.

      Length of Study:

      You may continue taking the study drug for as long as the doctor thinks it is in your best
      interest. You will no longer be able to take the study drug if the disease gets worse, if
      intolerable side effects occur, or if you are unable to follow study directions.

      Your participation on the study will be over after the follow-up visits.

      End-of-Dosing Visit:

      About 30 days after your last dose of study drug:

        -  You will have a physical exam.

        -  Blood (about 3 teaspoons) will be drawn for routine tests.

        -  If you the doctor thinks it is needed, blood (about ½ teaspoon) or urine will be
           collected for pregnancy testing.

      Follow Up Visits:

      Every 6 months you will be asked to come into the clinic or you will be called by a member of
      the study staff to ask how you are doing and if you have started any new anti-cancer
      treatments. If you are called, it should take about 10 minutes.

      This is an investigational study. Ibrutinib is FDA approved and commercially available for
      the treatment of chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). It is
      considered investigational to use this drug to treat NSCLC. The study doctor can explain how
      the study drug is designed to work.

      Up to 43 participants will be enrolled on this study. All will take part at MD Anderson.
    

Trial Arms

NameTypeDescriptionInterventions
IbrutinibExperimentalParticipants 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.
  • Ibrutinib

Eligibility Criteria

        Inclusion Criteria:

          1. 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.

          2. Patients must have measurable disease by Response Evaluation Criteria in Solid
             Tumors(RECIST) 1.1 criteria

          3. 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.

          4. 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.

          5. Age >/=18 years

          6. Eastern Cooperative Oncology Group (ECOG) performance status </=2

          7. Ability to take pills by mouth

          8. 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

          9. 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

         10. 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.

         11. Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          1. 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

          2. Prior treatment with ibrutinib

          3. Known hypersensitivity to ibrutinib

          4. Concurrent use of agents that strongly inhibit or induce CYP3A unless use is approved
             by the medical monitor

          5. 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

          6. Pregnant and nursing women

          7. 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

          8. Any gastrointestinal disorder expected to limit absorption of ibrutinib

          9. Treatment with warfarin or other vitamin K antagonist. Patients with using warfarin
             who switch to another form of anticoagulation will be eligible

         10. Patients with persistent and uncontrolled atrial fibrillation.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate
Time Frame:56 days
Safety Issue:
Description:Primary endpoint of this study is overall response rate using RECIST 1.1 criteria. Best overall response is best response recorded from start of treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since treatment started). Participant's best response assignment depends on achievement of both measurement and confirmation criteria.

Secondary Outcome Measures

Measure:Disease Control Rate
Time Frame:8 weeks
Safety Issue:
Description:Disease control rate defined as rate of complete response + partial response + stable disease. Complete Response (CR): Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis). Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Trial 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

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