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
Results First Posted : June 22, 2022
Last Update Posted : June 29, 2022
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Lung Non-Small Cell Carcinoma Stage IV Lung Non-Small Cell 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)|
|Actual Enrollment :||11 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|
|Actual Primary Completion Date :||September 3, 2021|
|Estimated Study Completion Date :||September 7, 2022|
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
- Number of Participants With at Least One Dose Limiting Toxicity (DLT) [ Time Frame: 28 days from the start of treatment. ]Adverse events were graded by CTCAE, v4. DLTs deﬁned as ≥Gr 3 non-hematologic toxicity except nausea, vomiting, or diarrhea that could be controlled by appropriate medical intervention or prophylaxis and that resolved within 48 hours, except electrolyte toxicities that can be corrected within 48 hours. Gr 3 rash attributed to the combination was considered a DLT if it remained Gr 3 despite maximal medical management for > 72 hours. Hematologic toxicities qualifying as DLTs included febrile neutropenia; Gr 4 neutropenia for > 7 days or thrombocytopenia < 25,000/mm3 (Gr 4) if associated with a bleeding event that did not result in hemodynamic instability but required an elective platelet transfusion; or a life-threatening bleeding event that resulted in urgent intervention and admission to an intensive care unit. Delay in starting cycle 2 of ≥14 days due to toxicity related to one or more protocol drugs was also considered a DLT. The ﬁrst 28-day cycle was considered the DLT period.
- Recommended Phase II Dose [ Time Frame: 28 days from start of treatment. ]The maximum tolerated dose (MTD) of Onalespib IV in combination with 150 mg Erlotinib PO daily is based on toxicities observed during the first cycle and is defined as the highest dose tested in which fewer than 33% of patients experience an attributable DLT to the study drug, when at least 6 patients are treated at that dose and are evaluable for toxicity. Dose escalations proceeded according to a standard 3+3 design.
- Number of Participants With Dose Limiting Toxicities. [ Time Frame: Up to 4 weeks ]During the first course of therapy patients will be monitored for dose-limiting toxicities (DLT). Dose escalation will follow a 3+3 design, motivated by the desire to limit the incidence of dose-limiting toxicity to the lowest feasible levels and determine the recommended phase II dose. This outcome measure has been addressed in primary outcome measures 1 & 2.
- Number of Subject With Overall Response [ Time Frame: Up to at least 1 year ]Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
- Progression-free Survival [ Time Frame: From start of treatment to time of progression or death from any cause, whichever occurs first, assessed up to at least 1 year ]Progression-free survival will be summarized as time from first protocol treatment until progression or death from any cause, using the product-limit Kaplan-Meier estimator. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
- Number of Subject With Overall Response (Recommended Phase II Dose) [ Time Frame: Up to at least 1 year ]
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI:
Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
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|