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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
14
Ipilimumab 3 mg/kg x 4 (given with standard Erlotinib or Crizotinib based on mutation)
Erlotinib 150 mg once daily or current tolerable dose (given with Ipilimumab)
Crizotinib 250 mg twice daily or current tolerable dose (given with Ipilimumab)
Huntsman Cancer Institute
Salt Lake City, Utah, United States
toxicity of ipilimumab and erlotinib in EGFR mutated patients
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.
Time frame: 36 months
toxicity of ipilimumab and crizotinib in ALK mutated patients
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.
Time frame: 36 months
toxicity of nivolumab and erlotinib in EGFR mutated patients
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.
Time frame: 36 months
toxicity of nivolumab and crizotinib in ALK mutated patients
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.
Time frame: 36 months
Response rate
Time frame: 36 months
Progression Free Survival (PFS)
Time frame: 36 months
Overall Survival
Time frame: 36 months
immune function pre and post immune therapy
The immune-related response criteria (irRC) incorporate several elements reflecting the complex tumor dynamics of ipilimumab 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. In this study, immune-related response criteria (irRC) will be used to assess subject response to study treatment per investigator assessment. The secondary endpoint irPFS will be determined based on investigator assessment. In order to adequately address this secondary objective, investigators will follow the clinical practice guidelines to obtain additional tumor assessments beyond mWHO PD and follow the instructions in this section for the determination of immune-related response.
Time frame: 36 months
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