Clinical Trials /

Low Dose Daily Erlotinib in Combination With High Dose Twice Weekly Erlotinib in Patients With EGFR-Mutant Lung Cancer

NCT01967095

Description:

The purpose of this study is to test the safety of different ways of taking erlotinib. The investigators want to find out what effects, good and/or bad, combination daily low dose and twice weekly high dose erlotinib has on the patient and lung cancer. The investigators are also seeing whether different schedules of erlotinib are better at treating lung cancer that has spread to the central nervous system. CNS expansion phase: The pulse continuous regimen will be then assess in patients with EGFR mutant lung cancers and CNS involvement. An additional expansion cohort (A) will enroll 19 patients with newly diagnosed EGFR mutant lung cancer with CNS involvement at diagnosis. The patients in the expansion cohorts will undergo the same treatment plan as the patients in the dose expansion cohort. A patient in the expansion cohorts will not be replaced if he/she does not finish the first 28 day (cycle 1) treatment period.

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

Completed

Phase:

Phase 1

Trial Eligibility

Document

Low Dose Daily <span class="go-doc-concept go-doc-intervention">Erlotinib</span> in Combination With High Dose Twice Weekly <span class="go-doc-concept go-doc-intervention">Erlotinib</span> in Patients With <span class="go-doc-concept go-doc-biomarker">EGFR</span>-<span class="go-doc-concept go-doc-keyword">Mutant</span> <span class="go-doc-concept go-doc-disease">Lung Cancer</span>

Title

  • Brief Title: Low Dose Daily Erlotinib in Combination With High Dose Twice Weekly Erlotinib in Patients With EGFR-Mutant Lung Cancer
  • Official Title: A Phase 1 Trial of Low Dose Daily Erlotinib in Combination With High Dose Twice Weekly Erlotinib in Patients With EGFR-Mutant Lung Cancer
  • Clinical Trial IDs

    NCT ID: NCT01967095

    ORG ID: 12-278

    Trial Conditions

    EGFR-Mutant Lung Cancer

    Trial Interventions

    Drug Synonyms Arms
    erlotinib The assigned dosing schedule will be repeated weekly x 3 to complete a 3 week, (21 day) cycle. Cycle 1 will be 4 weeks to account for one week of lead in, pulse dose erlotinib only. erlotinib

    Trial Purpose

    The purpose of this study is to test the safety of different ways of taking erlotinib. The
    investigators want to find out what effects, good and/or bad, combination daily low dose and
    twice weekly high dose erlotinib has on the patient and lung cancer. The investigators are
    also seeing whether different schedules of erlotinib are better at treating lung cancer that
    has spread to the central nervous system.

    CNS expansion phase:

    The pulse continuous regimen will be then assess in patients with EGFR mutant lung cancers
    and CNS involvement. An additional expansion cohort (A) will enroll 19 patients with newly
    diagnosed EGFR mutant lung cancer with CNS involvement at diagnosis. The patients in the
    expansion cohorts will undergo the same treatment plan as the patients in the dose expansion
    cohort. A patient in the expansion cohorts will not be replaced if he/she does not finish
    the first 28 day (cycle 1) treatment period.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    erlotinib Experimental This protocol is a phase 1, single arm, open label study of combination daily low dose erlotinib plus twice weekly high dose erlotinib in patients with EGFR-Mutant lung cancer who have not yet received erlotinib or gefitinib. Six dose levels are planned for escalation, with the pulse dose erlotinib increasing. Expansion cohort A: Treat an additional 19 pts at the MTD with CNS involvement at diagnosis erlotinib

    Eligibility Criteria

    Inclusion Criteria:

    - MSKCC pathologically-proven diagnosis locally advanced Stage III not amenable to
    definitive, curative treatment or Stage IV or recurrent non-small cell lung cancer

    - Documented presence of EGFR mutation confirmed by MSKCC or a local facility.

    - No prior treatment with erlotinib, gefitinib, or other EGFR tyrosine kinase
    inhibitors

    - Age 18 years

    - Measurable (RECIST 1.1) indicator lesion not previously irradiated.

    - Karnofsky Performance Status 70%

    - Ability to take oral medications

    - A negative serum pregnancy test obtained within 4 weeks prior to the start of
    treatment in all women of child-bearing potential.

    - All women of child bearing potential and sexually active men must agree to use
    adequate methods of birth control throughout the study which includes use of oral
    contraceptives with an additional barrier methods, double barrier methods,
    Depo-Provera, permanent sterilization of patient or partner or total abstinence.

    Expansion A:

    - brain metastases or leptomeningeal not previously treated with radiation or surgery

    Exclusion Criteria:

    - Inadequate recovery from any toxicity related to prior treatment (to Grade 2 or
    baseline).

    - Inadequate hematologic function defined as ANC < 1000 cells/mm, Platelet count
    <75,000/mm or Hemoglobin <9.0g/dL.

    - Inadequate hepatic function defined by AST/ALT >3x upper limit of normal (ULN), Total
    bilirubin>2x ULN, Alkaline phosphatase >3x ULN.

    - Symptomatic brain metastasis requiring radiation therapy or escalating doses of
    steroids.

    - Patients with clinically stable brain metastases or leptomeningeal disease
    (previously treated or untreated) are eligible. Patients in expansion cohort A must
    have at least one untreated CNS lesion

    - Women who are breastfeeding or pregnant.

    - Any evidence of clinically active interstitial lung disease.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    to determine the maximum tolerated dose (MTD)

    Secondary Outcome Measures

    to evaluate the safety profile

    Progression Free Survival (PFS)

    Response rate (RR)

    Overall survival (OS)

    Trial Keywords

    Erlotinib

    12-278

    CNS involvement