Erlotinib Hydrochloride and Onalespib Lactate in Treating Patients With Recurrent or Metastatic EGFR-Mutant Non-small Cell Lung Cancer
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|ClinicalTrials.gov Identifier: NCT02535338|
Recruitment Status : Active, not recruiting
First Posted : August 28, 2015
Last Update Posted : February 6, 2019
|Condition or disease||Intervention/treatment||Phase|
|EGFR Activating Mutation EGFR Exon 20 Insertion Mutation Recurrent Lung Non-Small Cell Carcinoma Stage IV Non-Small Cell Lung Cancer AJCC v7||Drug: Erlotinib Hydrochloride Other: Laboratory Biomarker Analysis Drug: Onalespib Lactate Other: Pharmacological Study||Phase 1 Phase 2|
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)
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).
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||46 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1/2 Trial of Erlotinib and Onalespib Lactate in EGFR-Mutant Non-Small Cell Lung Cancer|
|Actual Study Start Date :||January 21, 2016|
|Estimated Primary Completion Date :||June 30, 2019|
Experimental: Treatment (erlotinib hydrochloride, onalespib lactate)
Patients receive erlotinib hydrochloride PO daily and onalespib lactate 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.
Drug: Erlotinib Hydrochloride
Other: Laboratory Biomarker Analysis
Drug: Onalespib Lactate
Other: Pharmacological Study
- Incidence of dose-limiting toxicities from onalespib lactate in combination with erlotinib hydrochloride (Phase I) [ Time Frame: Up to 28 days ]Will be graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0
- Tumor response by Response Evaluation Criteria in Solid Tumors version 1.1 (Phase II) [ Time Frame: Up to at least 1 year ]Each cohort will be independently governed by Simon's two-stage minimax design, implemented to distinguish a 25% response rate from an assumed background rate of 5%, with 10% type I and type II error rates.
- Tumor response by Response Evaluation Criteria in Solid Tumors version 1.1 (Phase I) [ Time Frame: Up to at least 1 year ]Each cohort will be independently governed by Simon's two-stage minimax design, implemented to distinguish a 25% response rate from an assumed background rate of 5%, with 10% type I and type II error rates.
- Progression-free survival [ Time Frame: From start of treatment to time of progression or death, whichever occurs first, assessed up to at least 1 year ]Progression-free survival will be summarized for both cohorts as time from first protocol treatment, using the product-limit, Kaplan-Meier, estimator.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02535338
|United States, California|
|City of Hope Comprehensive Cancer Center|
|Duarte, California, United States, 91010|
|Los Angeles County-USC Medical Center|
|Los Angeles, California, United States, 90033|
|USC / Norris Comprehensive Cancer Center|
|Los Angeles, California, United States, 90033|
|Keck Medical Center of USC Pasadena|
|Pasadena, California, United States, 91105|
|University of California Davis Comprehensive Cancer Center|
|Sacramento, California, United States, 95817|
|City of Hope South Pasadena|
|South Pasadena, California, United States, 91030|
|Principal Investigator:||Jonathan W Riess||City of Hope Comprehensive Cancer Center LAO|