Afatinib and Necitumumab in Patients With EGFR Mutation Positive Advanced or Metastatic Non-small Cell Lung Cancer

NCT03054038 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: VICC THO 1684NCI-2016-01532
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 3

Brief Summary

This phase I trial studies the side effects and best dose of afatinib and necitumumab and to see how well they work in treating patients with EGFR mutation positive non-small cell lung cancer that has spread to other places in the body. Afatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as necitumumab, may interfere with the ability of tumor cells to grow and spread. Giving afatinib and necitumumab may work better in treating patients with EGFR mutation positive non-small cell lung cancer.

Conditions

Non-Small Cell Lung Carcinoma

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose experience a dose-limiting toxicity

  Highest dosage at which 0 or 1/6 patients

  Up to 28 days

Secondary Outcomes (5)

• Objective response rate

  Up to one year

• Objective response rate

  Up to one year

• Overall survival

  From the first dose of study treatment to the time of death from any cause on study, assessed up to 1 year

• Duration of response

  Up to 1 year

• Incidence of adverse events

  Up to 1 year

Study Arms (1)

Experimental

EXPERIMENTAL

Patients receive afatinib PO QD on days 1-28 and necitumumab IV over 60 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Afatinib; Biological: Necitumumab; Other: Laboratory Biomarker Analysis

Interventions

Afatinib DRUG

Given by mouth

Experimental

Necitumumab BIOLOGICAL

Given IV

Experimental

Laboratory Biomarker Analysis OTHER

Correlative studies

Experimental

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed and dated written informed consent
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
• Histologically or cytologically-confirmed advanced or metastatic non-small cell lung cancer (NSCLC) that is EGFR mutation positive; rare sensitizing mutations allowed
• Progression on a first generation EGFR TKI (T790M negative), or progression on a third generation TKI (if T790M positive at time of progression on a first or second generation TKI)
• At least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 that can be followed by computed tomography (CT) or magnetic resonance imaging (MRI)
• Patient consents to undergo a medically safe tumor biopsy at time of disease progression for mutation analysis
• Leukocytes \>= 3,000/uL
• Absolute neutrophil count (ANC) \>= 1,500/uL
• Platelets \>= 100,000/uL
• Hemoglobin \>= 9 g/dL
• Serum albumin \>= 2.5 g/dL
• Calculated creatinine clearance \> 50 mL/min (per the Cockcroft-Gault formula)
• Total bilirubin =\< 1.5 times upper limit of normal (ULN)
• Alkaline phosphatase (ALP) =\< 3.0 x ULN
• Alanine aminotransferase (ALT) and aspartate transaminase (AST) =\< 3.0 x ULN; for patients with hepatic metastases, ALT and AST =\< 5.0 x ULN are acceptable

You may not qualify if:

• Prior treatment against NSCLC with an EGFR monoclonal antibody
• Prior afatinib therapy, unless patient received an intervening third generation EGFR TKI after concluding prior afatinib and before enrollment on this clinical study
• Less than 3 days from prior treatment with EGFR TKI; patients with adverse events related to prior EGFR TKI must recover to Common Terminology Criteria for Adverse Events (CTCAE) =\< grade 1 to be eligible
• History of arterial or venous thromboembolism within 3 months prior to study enrollment; patients with a history of venous thromboembolism beyond 3 months prior to study enrollment can be enrolled if they are appropriately treated with low molecular weight heparin
• Subjects with a history of interstitial lung disease (e.g., sarcoidosis) that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity; subjects with chronic obstructive pulmonary disease (COPD) whose disease is controlled at study entry are allowed
• Symptomatic brain metastases; stable and treated central nervous system (CNS) disease allowed; patients with treated, asymptomatic brain metastases are eligible if there has been no change in brain disease status for at least two (2) weeks prior to initiating study treatment; anticonvulsant therapy will be allowed if patient is on a stable or decreasing dose of anticonvulsant treatment for at least two (2) weeks prior to initiating study treatment
• Subjects with carcinomatous meningitis
• Prior radiotherapy or radiosurgery \< 2 weeks prior to starting study treatment
• Current symptomatic congestive heart failure (New York Heart Association classification \>= grade III), unstable cardiac arrhythmia requiring therapy (e.g. medication or pacemaker), unstable angina (e.g. new, worsening or persistent chest discomfort), or uncontrolled hypertension (systolic \> 160 mmHg or diastolic \> 100 mmHg); or any of the following occurring within 6 months (180 days) prior to first dose of study treatment: myocardial infarction, coronary/peripheral artery bypass graft, cerebrovascular accident or transient ischemic attack; use of antihypertensive medication to control blood pressure is allowed
• Patient is pregnant or breastfeeding, or plans to become pregnant or father children from time of signing consent and lasting until 6 months after the last dose of trial treatment
• Previous or concomitant malignancies at other sites, except effectively treated non-melanoma skin cancers, carcinoma in situ of the cervix, ductal carcinoma in situ or effectively treated malignancy that has been in remission for more than 3 years and is considered to be cured AND no additional therapy is ongoing and required during the study period with the exception of bisphosphonates and anti-androgens and/or gonadorelin analogues for the treatment of prostate cancer are permitted; subjects with other active malignancy requiring concurrent intervention are excluded
• Requiring treatment with any of the prohibited concomitant medications listed that cannot be stopped for the duration of trial participation
• Any history or presence of poorly controlled gastrointestinal disorders that could affect the absorption of the study drug (e.g. Crohn's disease, ulcerative colitis, chronic diarrhea, malabsorption)
• Recent (within 30 days before enrollment) or concurrent yellow fever vaccination
• All toxicities attributed to prior anti-cancer therapy other than alopecia, fatigue, or peripheral neuropathy must have resolved to grade 1 (National Cancer Institute \[NCI\] CTCAE version 4) or baseline before administration of study drug

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead
• National Cancer Institute (NCI): collaborator
• National Comprehensive Cancer Network: collaborator

Study Sites (3)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

Stanford Cancer Institute

Stanford, California, 94035, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Afatinib; necitumumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Sally York, M.D.

  Vanderbilt-Ingram Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 25, 2016
• First Posted: February 15, 2017
• Study Start: July 20, 2017
• Primary Completion: March 23, 2022
• Study Completion: March 23, 2022
• Last Updated: April 14, 2022

Record last verified: 2022-04

Locations

US (3)