Itacitinib in Combination With Erlotinib in Non Small Cell Lung Cancer Patients With Epidermal Growth Factor Receptor (EGFR) Activating Mutations

Solid Tumors and Hematologic Malignancy Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02355431
• Other study ID #: INCB 39110-205
• Status: Withdrawn
• Phase: Phase 2
• Start date: December 2014
• Est. completion date: September 2015

Study information

• Verified date: March 2019
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: September 2015
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• NSCLC (Non-small Cell Lung Carcinoma)
• Solid Tumors and Hematologic Malignancy

Intervention

Drug:
• Itacitinib
tablets to be administered by mouth once daily at dose selected from safety run-in phase
• erlotinib
150 mg tablets administered by mouth once daily at total daily dose of 150 mg
• placebo
matching placebo tablets to be administered by mouth at dose selected from safety run-in phase

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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	Baseline through Day 21
Primary	Part 2: Overall Survival (OS)		Randomization until death. Approximately 31 months.
Primary	Part 2: Progression-free survival (PFS)	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.	Randomization to disease progression, or death due to any cause if sooner. Approximately 23 months.
Secondary	Part 2: Objective Response	Objective response determined by radiographic disease assessments per RECIST (v1.1), by investigator assessment	Baseline through end of study. Approximately 31 months.
Secondary	Part 2: Duration of Response	Duration of response determined by radiographic disease assessments per RECIST (v1.1), by investigator assessment Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.	Baseline through end of study. Approximately 31 months.
Secondary	Part 2: Safety and tolerability of the treatment regimens assessed by a summary of adverse events and clinical laboratory assessments.		Baseline through approximately 30 days post treatment discontinuation. Assessed after approximately 31 months.