Necitumumab and Trastuzumab in Combination With Osimertinib for the Treatment of Refractory Epidermal Growth Factor Receptor (EGFR)-Mutated Stage IV Non-small Cell Lung Cancer
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|ClinicalTrials.gov Identifier: NCT04285671|
Recruitment Status : Not yet recruiting
First Posted : February 26, 2020
Last Update Posted : September 18, 2020
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Lung Non-Small Cell Carcinoma Refractory Lung Non-Small Cell Carcinoma Stage IV Lung Cancer American Joint Committee on Cancer (AJCC) v8 Stage IVA Lung Cancer AJCC v8 Stage IVB Lung Cancer AJCC v8||Biological: Necitumumab Drug: Osimertinib Other: Quality-of-Life Assessment Other: Questionnaire Administration Biological: Trastuzumab||Phase 1 Phase 2|
I. Determine the recommended phase II dose (RP2D) of osimertinib and necitumumab in combination with trastuzumab. (Phase Ib) II. Evaluate the efficacy of osimertinib, necitumumab, and trastuzumab (ONT) as measured by objective response rate (ORR), which is defined as complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. (Phase II)
I. To evaluate the efficacy of ONT as measured progression free survival (PFS), duration of response (DoR), and overall survival (OS).
II. To evaluate the safety and tolerability of ONT as measured by adverse events (AEs) defined by Common Terminology Criteria for Adverse Events version 5.0 (CTCAE V 5.0).
I. To assess patient-reported outcomes on health-related quality of life and adverse events.
II. Assess potential biomarkers associated with response from liquid biopsies and optional but recommended baseline tissue biopsy.
IIa. Correlate pre-and post-treatment biopsies molecular changes with response. III. Correlate mutant allele fraction in circulating tumor deoxyribonucleic acid (DNA) (ctDNA) via liquid biopsy with response.
OUTLINE: This is a phase Ib, dose-escalation study of osimertinib and necitumumab followed by a phase II study.
Patients receive necitumumab intravenously (IV) over 60 minutes and trastuzumab IV over 30-90 minutes on days 1 and 15. Patients also receive osimertinib orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After the completion of study treatment, patients are followed up at 30 days, every 8 weeks through week 24, then every 12 weeks up to 1 year.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||26 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||UCLA L-08: A Phase Ib/II Study of Combined HER Inhibition Adding Necitumumab and Trastuzumab to Osimertinib in Patients With Refractory EGFR-Mutated Lung Cancer|
|Estimated Study Start Date :||December 1, 2020|
|Estimated Primary Completion Date :||December 2, 2022|
|Estimated Study Completion Date :||December 2, 2023|
Experimental: Treatment (necitumumab, trastuzumab, osimertinib)
Patients receive necitumumab IV over 60 minutes and trastuzumab IV over 30-90 minutes on days 1 and 15. Patients also receive osimertinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other: Quality-of-Life Assessment
Other Name: Quality of Life Assessment
Other: Questionnaire Administration
- Identification of the recommended phase II dose (R2PD) regimen for combination osimertinib, necitumumab, trastuzumab (ONT) therapy (Phase Ib) [ Time Frame: Up to 1 year ]
- Incidence of adverse events (Phase Ib) [ Time Frame: Up to 1 year ]Will be defined by the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE V5.0).
- Objective response rate (ORR) (Phase II) [ Time Frame: Up to 1 year ]Will be based on the Full Analysis Set (FAS) of the phase II portion of the trial and the phase Ib patients treated at the recommended phase II dose (RP2D). ORR is defined as defined as complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Will be determined by the investigator. A Cox proportional hazards model will be used to estimate the hazard ratio and its 95% confidence interval (CI).
- Progression free survival (PFS) (Phase II) [ Time Frame: Up to 1 year ]PFS is defined as the time from trial initiation to cancer progression per RECIST 1.1 based on investigator assessment or death due to any cause.
- Duration of response (DoR) (Phase II) [ Time Frame: Up to 1 year ]DoR is time from documentation of tumor response to disease progression.
- Overall survival (OS) (Phase II) [ Time Frame: Up to 1 year ]OS is defined as time from randomization to death by any cause.
- Time to response (TTR) [ Time Frame: Up to 1 year ]
- Patient reported outcomes (PROs) [ Time Frame: Up to 1 year ]Will be assessed using Patient Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE).
- Quality of life data questionnaire [ Time Frame: Up to 1 year ]Will be obtained from the Functional Assessment of Cancer Therapy - Lung (FACT-L) questionnaire. Will be analyzed by the clinical biostatisticians in the University of California, Los Angeles (UCLA) Department of Medicine Medical Statistics Core.
- Potential biomarkers associated with response from liquid biopsies [ Time Frame: Up to 1 year ]Will be assessed using response from liquid biopsies and optional but recommended baseline tissue biopsy. Will correlate pre-and post-treatment biopsies molecular changes (i.e. expression of HER2, HER3, AXL, MET) with response.
- Mutant allele fraction in circulating tumor deoxyribonucleic acid (DNA) (ctDNA) [ Time Frame: Up to 1 year ]Will be assessed using liquid biopsy with response.
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): NCT04285671
|Contact: Karla Russell||310 firstname.lastname@example.org|
|United States, California|
|UCLA / Jonsson Comprehensive Cancer Center|
|Los Angeles, California, United States, 90095|
|Contact: Jonathan W. Goldman 310-633-8400 Jwgoldman@mednet.ucla.edu|
|Principal Investigator: Jonathan W. Goldman|
|Principal Investigator:||Jonathan W Goldman||UCLA / Jonsson Comprehensive Cancer Center|