NCT02535338

Erlotinib Hydrochloride and Onalespib Lactate in Treating Patients With Recurrent or Metastatic EGFR-Mutant Non-small Cell Lung Cancer

A Phase 1/2 Trial of Erlotinib and Onalespib Lactate in EGFR-Mutant Non-Small Cell Lung Cancer

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 11 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I/II trial studies the side effects and best dose of onalespib lactate when given together with erlotinib hydrochloride and to see how well they work in treating patients with EGFR-mutant non-small cell lung cancer that has come back (recurrent) or has spread to other places in the body (metastatic). Erlotinib hydrochloride and onalespib lactate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed description

PRIMARY OBJECTIVES: I. To determine the safety and tolerability of erlotinib hydrochloride (erlotinib) and onalespib lactate (onalespib) in patients with EGFR-mutant non-small cell lung cancer (NSCLC). (PHASE I) II. To preliminarily assess efficacy of combination erlotinib and onalespib at the recommended phase II dose (RP2D) determined in the phase I portion of the study in EGFR-mutant NSCLC patients who have not had a complete or partial response by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 to frontline erlotinib after a minimum of 12 weeks on erlotinib. (PHASE II, COHORT A) III. To preliminarily assess efficacy of combination erlotinib and onalespib at the RP2D in NSCLC patients whose tumor harbors an EGFR exon 20 insertion (an EGFR mutation not typically responsive to single agent erlotinib). (PHASE II, COHORT B) SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity (primary aim phase II, secondary aim phase I). II. To evaluate in a preliminary manner the progression-free survival (PFS) and disease control rate (DCR) of patients treated with erlotinib/onalespib. III. To characterize the pharmacokinetics of the above drug combinations at the recommended phase II dose (RP2D). TERTIARY OBJECTIVES: I. To explore plasma EGFR-mutant deoxyribonucleic acid (DNA) as a biomarker by detecting changes in plasma EGFR-mutant DNA levels (including plasma EGFR-T790M) and new mutations that may represent resistance to treatment. II. To demonstrate knockdown of Hsp90 client oncoproteins via treatment with erlotinib and onalespib by multiplexed immunofluorescence in serial tumor biopsies. III. To establish patient derived xenotransplant models in EGFR-mutated NSCLC with a focus on tumors that lack response to single agent erlotinib and in patients with tumors harboring EGFR exon 20 insertions. OUTLINE: This is a phase I, dose-escalation study of onalespib lactate followed by a phase II study. Patients receive erlotinib hydrochloride orally (PO) daily and onalespib lactate intravenously (IV) over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for at least 3 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 12 weeks for 1 year and then annually thereafter.

Conditions

• Recurrent Lung Non-Small Cell Carcinoma
• Stage IV Lung Non-Small Cell Cancer AJCC v7

Interventions

Type	Name	Description
DRUG	Erlotinib Hydrochloride	Given PO
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	Onalespib Lactate	Given IV
OTHER	Pharmacological Study	Correlative studies

Timeline

• Start date: 2016-04-11
• Primary completion: 2021-09-03
• Completion: 2021-09-08
• First posted: 2015-08-28
• Last updated: 2025-03-03
• Results posted: 2022-06-22

Locations

6 sites across 1 country: United States