Brief Summary
The purpose of this study is to determine if Itacitinib in combination with erlotinib is safe and effective in the treatment of nonsquamous non-small cell lung cancer (NSCLC) that is Stage IIIB/Stage IV or recurrent whose tumors have EGFR activating mutations.
Brief Title
Itacitinib in Combination With Erlotinib in Non Small Cell Lung Cancer Patients With Epidermal Growth Factor Receptor (EGFR) Activating Mutations
Detailed Description
The study consists of an open-label, safety run-in to confirm the safety of Itacitinibin combination with erlotinib in subjects with nonsquamous non-small cell lung cancer (NSCLC) that is Stage IIIB, Stage IV, or recurrent whose tumors have EGFR activating mutations. Subjects in the safety run-in will receive open-label Itacitinib and erlotinib.
In the second part of the study, subjects will be enrolled and randomized to receive erlotinib (open-label) and either Itacitinib or placebo in a blinded manner. The dose of Itacitinib administered will be determined from the data produced in the safety run-in phase.
Treatment will consist of repeating 21-day cycles. Subjects will take erlotinib tablets daily and Itacitinib/placebo will be self-administered daily during the entire cycle.
In the second part of the study, subjects will be enrolled and randomized to receive erlotinib (open-label) and either Itacitinib or placebo in a blinded manner. The dose of Itacitinib administered will be determined from the data produced in the safety run-in phase.
Treatment will consist of repeating 21-day cycles. Subjects will take erlotinib tablets daily and Itacitinib/placebo will be self-administered daily during the entire cycle.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Solid Tumors and Hematologic Malignancy
NSCLC (Non-small Cell Lung Carcinoma)
Eligibility Criteria
Inclusion Criteria:
* Histologically or cytologically confirmed diagnosis of nonsquamous NSCLC that is Stage IIIB, Stage IV, or recurrent (including Stage II).
* Documented evidence of an activating mutation in EGFR in tumor samples (exon 19 deletions or point mutation L858R in exon 21 or point mutations at codon 719).
* A mGPS of 1 or 2 as defined below:
* Criteria: C-reactive protein \>10 mg/L AND albumin ≥35 g/L Score-1
* Criteria: C-reactive protein \>10 mg L AND albumin \<35 g/L Score-2
* Radiographically measurable or evaluable disease.
* Life expectancy of at least 12 weeks.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
* Adequate renal, hepatic, and bone marrow function demonstrated by protocol-specified laboratory parameters at the screening visit.
Exclusion Criteria:
* Known presence of the T790M mutation in EGFR in tumor samples
* Candidates for curative radiation therapy or surgery.
* Previous systemic chemotherapy for advanced disease, including EGFR inhibitor therapy, except subjects who received 1 cycle of chemotherapy while waiting to receive EGFR results, who may enroll provided that 21 days have elapsed from end of chemotherapy to the day to the baseline radiographic measurement prior to Cycle 1 Day 1.
* Distinct or suspected, or history of, pulmonary fibrosis or ILD.
* Current or previous other malignancy within 2 years of study entry, except cured basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive indolent or Stage I malignancy without sponsor approval.
* Histologically or cytologically confirmed diagnosis of nonsquamous NSCLC that is Stage IIIB, Stage IV, or recurrent (including Stage II).
* Documented evidence of an activating mutation in EGFR in tumor samples (exon 19 deletions or point mutation L858R in exon 21 or point mutations at codon 719).
* A mGPS of 1 or 2 as defined below:
* Criteria: C-reactive protein \>10 mg/L AND albumin ≥35 g/L Score-1
* Criteria: C-reactive protein \>10 mg L AND albumin \<35 g/L Score-2
* Radiographically measurable or evaluable disease.
* Life expectancy of at least 12 weeks.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
* Adequate renal, hepatic, and bone marrow function demonstrated by protocol-specified laboratory parameters at the screening visit.
Exclusion Criteria:
* Known presence of the T790M mutation in EGFR in tumor samples
* Candidates for curative radiation therapy or surgery.
* Previous systemic chemotherapy for advanced disease, including EGFR inhibitor therapy, except subjects who received 1 cycle of chemotherapy while waiting to receive EGFR results, who may enroll provided that 21 days have elapsed from end of chemotherapy to the day to the baseline radiographic measurement prior to Cycle 1 Day 1.
* Distinct or suspected, or history of, pulmonary fibrosis or ILD.
* Current or previous other malignancy within 2 years of study entry, except cured basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive indolent or Stage I malignancy without sponsor approval.
Inclusion Criteria
Inclusion Criteria:
* Histologically or cytologically confirmed diagnosis of nonsquamous NSCLC that is Stage IIIB, Stage IV, or recurrent (including Stage II).
* Documented evidence of an activating mutation in EGFR in tumor samples (exon 19 deletions or point mutation L858R in exon 21 or point mutations at codon 719).
* A mGPS of 1 or 2 as defined below:
* Criteria: C-reactive protein \>10 mg/L AND albumin ≥35 g/L Score-1
* Criteria: C-reactive protein \>10 mg L AND albumin \<35 g/L Score-2
* Radiographically measurable or evaluable disease.
* Life expectancy of at least 12 weeks.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
* Adequate renal, hepatic, and bone marrow function demonstrated by protocol-specified laboratory parameters at the screening visit.
* Histologically or cytologically confirmed diagnosis of nonsquamous NSCLC that is Stage IIIB, Stage IV, or recurrent (including Stage II).
* Documented evidence of an activating mutation in EGFR in tumor samples (exon 19 deletions or point mutation L858R in exon 21 or point mutations at codon 719).
* A mGPS of 1 or 2 as defined below:
* Criteria: C-reactive protein \>10 mg/L AND albumin ≥35 g/L Score-1
* Criteria: C-reactive protein \>10 mg L AND albumin \<35 g/L Score-2
* Radiographically measurable or evaluable disease.
* Life expectancy of at least 12 weeks.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
* Adequate renal, hepatic, and bone marrow function demonstrated by protocol-specified laboratory parameters at the screening visit.
Gender
All
Gender Based
false
Keywords
EGFR
mutation
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02355431
Org Class
Industry
Org Full Name
Incyte Corporation
Org Study Id
INCB 39110-205
Overall Status
Withdrawn
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Randomized, Double-blind Phase 2 Study of Itacitinib in Combination With Erlotinib Versus Erlotinib Alone in Subjects With Stage IIIB/ IV or Recurrent Non-Small Cell Lung Cancer (NSCLC) Whose Tumors Have Epidermal Growth Factor Receptor (EGFR) Activating Mutations
Primary Outcomes
Outcome Description
Subjects will take erlotinib daily and begin dosing with itacitinib once daily (QD) on Cycle 1, Day 1. The safety and tolerability of the regimen will be assessed during the first 21 days of therapy
Outcome Measure
Part 1: Determination of the dose of itacitinib that is safe and tolerable in combination with erlotinib as measured by the number of dose-limiting toxicities (DLTs) observed in the evaluation cohort.
Outcome Time Frame
Baseline through Day 21
Outcome Measure
Part 2: Overall Survival (OS)
Outcome Time Frame
Randomization until death. Approximately 31 months.
Outcome Description
PFS is defined as the time from randomization until the earliest date of disease progression determined by investigator assessment of objective radiographic disease assessments per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death due to any cause if sooner.
Outcome Measure
Part 2: Progression-free survival (PFS)
Outcome Time Frame
Randomization to disease progression, or death due to any cause if sooner. Approximately 23 months.
Secondary Outcomes
Outcome Description
Objective response determined by radiographic disease assessments per RECIST (v1.1), by investigator assessment
Outcome Time Frame
Baseline through end of study. Approximately 31 months.
Outcome Measure
Part 2: Objective Response
Outcome Description
Duration of response determined by radiographic disease assessments per RECIST (v1.1), by investigator assessment Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Outcome Time Frame
Baseline through end of study. Approximately 31 months.
Outcome Measure
Part 2: Duration of Response
Outcome Time Frame
Baseline through approximately 30 days post treatment discontinuation. Assessed after approximately 31 months.
Outcome Measure
Part 2: Safety and tolerability of the treatment regimens assessed by a summary of adverse events and clinical laboratory assessments.
Start Date
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Balazs Halmos
Investigator Email
bahalmos@montefiore.org
Investigator Phone
Categories Mesh Debug
Blood & Bone Marrow Cancers --- HEMATOLOGIC NEOPLASMS
Lung & Chest Cancers --- CARCINOMA, NON-SMALL-CELL LUNG
Cancer --- NEOPLASMS BY SITE
Cancer --- NEOPLASMS
Blood Disorders --- HEMATOLOGIC DISEASES
Blood & Bone Marrow Cancers --- HEMATOLOGIC DISEASES
Lung & Chest Cancers --- CARCINOMA, BRONCHOGENIC
Lung & Chest Cancers --- BRONCHIAL NEOPLASMS
Lung & Chest Cancers --- LUNG NEOPLASMS
Lung & Chest Cancers --- RESPIRATORY TRACT NEOPLASMS
Lung & Chest Cancers --- THORACIC NEOPLASMS
Lung & Chest Cancers --- LUNG DISEASES
COVID-19 --- LUNG DISEASES
Lung --- LUNG DISEASES
Asthma and Other Respiratory Diseases --- RESPIRATORY TRACT DISEASES
Lung & Chest Cancers --- RESPIRATORY TRACT DISEASES
COVID-19 --- RESPIRATORY TRACT DISEASES
Lung --- RESPIRATORY TRACT DISEASES
MeSH Terms
HEMATOLOGIC NEOPLASMS
CARCINOMA, NON-SMALL-CELL LUNG
NEOPLASMS BY SITE
NEOPLASMS
HEMATOLOGIC DISEASES
HEMIC AND LYMPHATIC DISEASES
CARCINOMA, BRONCHOGENIC
BRONCHIAL NEOPLASMS
LUNG NEOPLASMS
RESPIRATORY TRACT NEOPLASMS
THORACIC NEOPLASMS
LUNG DISEASES
RESPIRATORY TRACT DISEASES
ITACITINIB
INCB039110
ERLOTINIB HYDROCHLORIDE
COUNTERFEIT DRUGS
QUINAZOLINES
HETEROCYCLIC COMPOUNDS, 2-RING
HETEROCYCLIC COMPOUNDS, FUSED-RING
HETEROCYCLIC COMPOUNDS
SUBSTANDARD DRUGS
PHARMACEUTICAL PREPARATIONS