Clinical Trials /

Combination Checkpoint Inhibitor Plus Erlotinib or Crizotinib for EGFR or ALK Mutated Stage IV Non-small Cell Lung Cancer

NCT01998126

Description:

The goals of the overall study are to evaluate a recommended phase 2 dose and the short and long term toxicities of the combinations. This is a modified phase I trial of immune checkpoint inhibitors in combination with mutation - specific targeted therapy (crizotinib or erlotinib) at conventional doses stratified for presence of ALK (Anaplastic lymphoma kinase) or EGFR (epidermal growth factor receptor) mutation. The goals of the overall study are to evaluate a recommended phase 2 dose and the short and long term toxicities of the combinations.

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

Completed

Phase:

Phase 1

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Ipilimumab</span> Plus Targeted Inhibitor (<span class="go-doc-concept go-doc-intervention">Erlotinib</span> or <span class="go-doc-concept go-doc-intervention">Crizotinib</span>) for <span class="go-doc-concept go-doc-biomarker">EGFR</span> or <span class="go-doc-concept go-doc-biomarker">ALK</span> <span class="go-doc-concept go-doc-keyword">Mutated</span> Stage IV Non-small Cell <span class="go-doc-concept go-doc-disease">Lung Cancer</span>: Phase Ib With Expansion Cohorts

Title

  • Brief Title: Ipilimumab Plus Targeted Inhibitor (Erlotinib or Crizotinib) for EGFR or ALK Mutated Stage IV Non-small Cell Lung Cancer: Phase Ib With Expansion Cohorts
  • Official Title: Ipilimumab Plus Targeted Inhibitor (Erlotinib or Crizotinib) for EGFR or ALK Mutated Stage IV Non-small Cell Lung Cancer: Phase Ib With Expansion Cohorts
  • Clinical Trial IDs

    NCT ID: NCT01998126

    ORG ID: HCI66705

    Trial Conditions

    Non-small Cell Lung Cancer

    Trial Interventions

    Drug Synonyms Arms
    Ipilimumab Yervoy EGFR patients, ALK patients
    Erlotinib EGFR patients
    Crizotinib ALK patients

    Trial Purpose

    This is a modified phase I trial of ipilimumab in combination with mutation - specific
    targeted therapy (crizotinib or erlotinib) at conventional doses stratified for presence of
    ALK (Anaplastic lymphoma kinase) or EGFR (epidermal growth factor receptor) mutation.
    Ipilimumab will be tested at a single level of 3 mg/kg for both ALK and EGFR mutated groups
    with expansion cohorts for each group to better characterize long term effects of
    combination therapy.

    The goals of the overall study are to evaluate a recommended phase 2 dose and the short and
    long term toxicities of the combinations.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    EGFR patients Experimental ipilimumab and erlotinib in EGFR mutated patients Ipilimumab, Erlotinib
    ALK patients Experimental ipilimumab and crizotinib in ALK mutated patients Ipilimumab, Crizotinib

    Eligibility Criteria

    Inclusion Criteria:

    - Histological or cytological diagnosis of Stage IV Non-Small Cell Lung Cancer (NSCLC)
    that is either EGFR or ALK mutated.

    - Untreated with/or actively treated with specific inhibitor for less than 6 months if
    not progressing on active therapy.

    - Age > 18.

    - ECOG performance status 0, 1 or 2.

    - Prior chemotherapy is allowed if > one month. Patients must not have received
    chemotherapy within 4 weeks of the start of study drug.

    - Brain metastases are allowed if the patient is asymptomatic or previous steroid
    treatment was discontinued > 6 weeks.

    - Adequate bone marrow function as defined by:

    - White Blood Count (WBC) > 2.0 g/dL

    - Hemoglobin > 9.0 g/dL

    - Absolute neutrophil count (ANC) > 1,000/mm3

    - Platelets > 100,000/mm3

    - Serum bilirubin levels < 1.5 mg/dL except for patients with Gilbert's syndrome.

    - Adequate organ function as defined by:

    - Serum aspartate transaminase (AST) < 2.5 X upper limit of normal.

    - Serum alanine transaminase (ALT) < 2.5 X upper limit of normal.

    - If female and of childbearing potential, documentation of negative pregnancy test
    (serum or urine) within 7 days prior to first dose.

    - Able to provide informed consent and have signed an approved consent form that
    conforms to federal and institutional guidelines.

    Exclusion Criteria:

    - Concurrent therapy with any other non-protocol anti-cancer therapy.

    - History of any other malignancy requiring active treatment.

    - Patients who have had a history of acute diverticulitis, intra-abdominal abscess,
    Gastrointestical obstruction and abdominal carcinomatosis which are known risk
    factors for bowel perforation.

    - History of symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic
    progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune
    vasculitis [e.g., Wegener's Granulomatosis]); motor neuropathy considered of
    autoimmune origin (e.g., Guillain-Barre Syndrome). History of vitiligo and adequately
    controlled endocrine deficiencies such as hypothyroidism are allowed.

    - Significant cardiovascular disease including:

    - Active, clinically symptomatic left ventricular failure.

    - Uncontrolled symptomatic hypertension that cannot be controlled with
    anti-hypertensive agents.

    - Myocardial infarction, severe angina, or unstable angina within 6 months prior
    to administration of first dose of study drug.

    - History of serious ventricular arrhythmia (i.e., ventricular tachycardia or
    ventricular fibrillation)

    - Cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial
    fibrillation that is well controlled with anti-arrhythmic medication)

    - Coronary or peripheral artery bypass graft within 6 months of screening.

    - Uncontrolled CNS metastases are not allowed; subjects with previously treated brain
    metastases will be allowed if the brain metastases have been treated, toxicities have
    resolved to grade 1 or baseline and steroids are no longer required. Leptomeningeal
    metastases are not allowed.

    - Serious/active infection or infection requiring parenteral antibiotics.

    - Pregnant or lactating females.

    - HIV infection or chronic hepatitis B or C. Negative Screening tests for HIV,
    Hepatitis B, and Hepatitis C are required.

    - The presence of any other medical or psychiatric disorder that, in the opinion of the
    treating physician, would contraindicate the use of the drugs in this protocol or
    place the subject at undue risk for treatment complications.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    toxicity of ipilimumab and erlotinib in EGFR mutated patients and toxicity of ipilimumab and crizotinib in ALK mutated patients with Non-small cell lung cancer

    Secondary Outcome Measures

    Response rate

    Progression Free Survival (PFS)

    Overall Survival

    immune function pre and post immune therapy

    Trial Keywords