Evaluation of Combination Checkpoint Inhibitor Plus Targeted Inhibitor (Erlotinib or Crizotinib) for EGFR or ALK Mutated Stage IV Non-small Cell Lung Cancer: Phase Ib With Expansion Cohorts
Overview
- Phase
- Phase 1
- Intervention
- Erlotinib
- Conditions
- Non-small Cell Lung Cancer
- Sponsor
- University of Utah
- Enrollment
- 14
- Locations
- 1
- Primary Endpoint
- toxicity of ipilimumab and erlotinib in EGFR mutated patients
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Diagnosis of Stage IV Non-Small Cell Lung Cancer (NSCLC), or Stages II - III NSCLC that cannot be treated curatively with standard techniques.
- •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.
- •ECOG performance status 0, 1 or
- •Prior chemotherapy is allowed if \> one month from the end of treatment. 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 in the protocol
- •Serum bilirubin levels \< 1.5 mg/dL except for patients with Gilbert's syndrome.
- •Adequate organ function as defined in the protocol
- •If female and of childbearing potential, documentation of negative pregnancy test (serum or urine) within 7 days prior to first dose.
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)
Arms & Interventions
EGFR patients with nivolumab
nivolumab and erlotinib in EGFR mutated patients
Intervention: Erlotinib
EGFR patients with ipilimumab
ipilimumab and erlotinib in EGFR mutated patients
Intervention: Ipilimumab
EGFR patients with ipilimumab
ipilimumab and erlotinib in EGFR mutated patients
Intervention: Erlotinib
ALK patients plus ipilimumab
ipilimumab and crizotinib in ALK mutated patients
Intervention: Ipilimumab
ALK patients plus ipilimumab
ipilimumab and crizotinib in ALK mutated patients
Intervention: Crizotinib
EGFR patients with nivolumab
nivolumab and erlotinib in EGFR mutated patients
Intervention: Nivolumab
ALK patients plus nivolumab
nivolumab and crizotinib in ALK mutated patients
Intervention: Crizotinib
ALK patients plus nivolumab
nivolumab and crizotinib in ALK mutated patients
Intervention: Nivolumab
Outcomes
Primary Outcomes
toxicity of ipilimumab and erlotinib in EGFR mutated patients
Time Frame: 36 months
The immune-related response criteria (irRC) incorporate several elements reflecting the complex tumor dynamics of ipilimumab/nivolumab treatment. Under these criteria, a measure of tumor volume is used that incorporates the contribution of new measurable lesions. Each net percentage change in tumor burden per assessment using irRC accounts for the size and growth kinetics of both old and new lesions as they appear. New lesions alone do not qualify as immune-related progressive disease.
toxicity of nivolumab and erlotinib in EGFR mutated patients
Time Frame: 36 months
The immune-related response criteria (irRC) incorporate several elements reflecting the complex tumor dynamics of ipilimumab/nivolumab treatment. Under these criteria, a measure of tumor volume is used that incorporates the contribution of new measurable lesions. Each net percentage change in tumor burden per assessment using irRC accounts for the size and growth kinetics of both old and new lesions as they appear. New lesions alone do not qualify as immune-related progressive disease.
toxicity of ipilimumab and crizotinib in ALK mutated patients
Time Frame: 36 months
The immune-related response criteria (irRC) incorporate several elements reflecting the complex tumor dynamics of ipilimumab/nivolumab treatment. Under these criteria, a measure of tumor volume is used that incorporates the contribution of new measurable lesions. Each net percentage change in tumor burden per assessment using irRC accounts for the size and growth kinetics of both old and new lesions as they appear. New lesions alone do not qualify as immune-related progressive disease.
toxicity of nivolumab and crizotinib in ALK mutated patients
Time Frame: 36 months
The immune-related response criteria (irRC) incorporate several elements reflecting the complex tumor dynamics of ipilimumab/nivolumab treatment. Under these criteria, a measure of tumor volume is used that incorporates the contribution of new measurable lesions. Each net percentage change in tumor burden per assessment using irRC accounts for the size and growth kinetics of both old and new lesions as they appear. New lesions alone do not qualify as immune-related progressive disease.
Secondary Outcomes
- Response rate(36 months)
- Progression Free Survival (PFS)(36 months)
- Overall Survival(36 months)
- immune function pre and post immune therapy(36 months)