Non-Small Cell Lung CarcinomaPhase 1NCT03054038
Afatinib and Necitumumab in Patients With EGFR Mutation Positive Advanced or Metastatic Non-small Cell Lung Cancer
A Phase 1 study testing Afatinib, Necitumumab and Laboratory Biomarker Analysis in people with Non-Small Cell Lung Carcinoma, run by Vanderbilt-Ingram Cancer Center at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Small Cell Lung Carcinoma
- What is being tested?
- Afatinib, Necitumumab and Laboratory Biomarker Analysis
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 3 sitesUnited States
- Study dates
- 20 Jul 2017to 23 Mar 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
- Note: if a patient experiences elevated ALT > 5 x ULN and elevated total bilirubin > 2 x ULN, clinical and laboratory monitoring should be initiated by the investigator; for patients entering the study with ALT > 3 x ULN, monitoring should be triggered at ALT > 2 x baseline
- Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 14 days prior to receiving first dose of study medication; and additionally agree to use at least two methods of birth control or abstain from heterosexual intercourse from the time of signing consent, and until 6 months after patient's last dose of study drug
- WOCBP of childbearing potential are defined as those not surgically sterile or not post-menopausal (i.e. if a female patient has not had a bilateral tubal ligation, a bilateral oophorectomy, or a complete hysterectomy; or has not been amenorrheic for 24 months in the absence of an alternative medical cause, then patient will be considered a female of childbearing potential); postmenopausal status in females under 55 years of age should be confirmed with a serum follicle-stimulating hormone (FSH) level within laboratory reference range for postmenopausal women
- WOCBP must agree to follow instructions for method(s) of contraception from the time of signing consent and until 6 months after last dose of study therapy
- Men able to father children who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception from the time of signing consent and until 6 months after last dose of study therapy; men able to father children are defined as those who are not surgically sterile (i.e. patient has not had a vasectomy)
Who cannot join
- 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
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- 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
- The patient has any ongoing or active infection, including active tuberculosis; Note: a urinary tract infection controlled with oral antibiotics initiated at least 7 days prior to study entry is acceptable
- Known positive test for hepatitis B, hepatitis C, human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS)
- The patient has a known allergy/history of hypersensitivity reaction to any of the treatment components, including any ingredient used in the formulation of necitumumab, or any other contraindication to one of the administered treatments
- Known hypersensitivity to afatinib or the excipients of any of the trial drugs
- History of severe hypersensitivity reactions to other monoclonal antibodies
- Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g. infectious disease) illness
- Any other serious or uncontrolled medical disorder, active infection, physical exam finding, laboratory finding, altered mental status, or psychiatric condition that, in the opinion of the investigator, would limit a subject's ability to comply with the study requirements, substantially increase risk to the subject, or impact the interpretability of study results
Trial locations and contacts
3 sites in 1 country.
United States3 sites
City of Hope National Medical Center
Duarte, California, 91010
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232
Stanford Cancer Institute
Stanford, California, 94035
About this study
Official title: Phase I Trial of Combination Afatinib and Necitumumab in EGFR Mutation Positive NSCLC With Acquired Resistance to First or Third Generation EGFR TKIs
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.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the maximum tolerated dose of combination afatinib and necitumumab therapy in EGFR mutation positive non-small cell lung cancer (NSCLC) patients who have progressed following first- and third-generation EGFR tyrosine kinase inhibitors (TKIs).
II. To determine the efficacy and safety profile of afatinib and necitumumab combination therapy in patients with EGFR mutation positive NSCLC patients who have progressed following first- and third-generation EGFR TKIs.
OUTLINE: This is a dose-escalation study.
Patients receive afatinib orally (PO) once daily (QD) on days 1-28 and necitumumab intravenously (IV) over 60 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 28 days and then every 3 months for up to 1 year.
- Conditions
- Non-Small Cell Lung Carcinoma
- Being tested
- Afatinib, Necitumumab, Laboratory Biomarker Analysis
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AfatinibDrug
Given by mouth
NecitumumabBiological
Given IV
Laboratory Biomarker AnalysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Afatinib; Biological: Necitumumab; Other: Laboratory Biomarker Analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose experience a dose-limiting toxicity
Highest dosage at which 0 or 1/6 patients
Measured: Up to 28 days
Secondary outcomes (5)
Objective response rate
Complete response assessed by RECIST version (v) 1.1
Measured: Up to one year
Objective response rate
Partial response assessed by RECIST version (v) 1.1
Measured: Up to one year
Overall survival
Assessed by RECIST v1.1
Measured: 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
Assessed by RECIST v1.1
Measured: Up to 1 year
Incidence of adverse events
Assessed by NCI CTCAE
Measured: Up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2017
- Study start20 Jul 2017
- Primary completion23 Mar 2022
- Study completion23 Mar 2022
Why it stopped: Low accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Small Cell Lung CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt-Ingram Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), National Comprehensive Cancer Network
- Responsible party
- Principal investigator, Sally York, Vanderbilt-Ingram Cancer Center
- Investigators
- Sally York, M.D., Principal investigator, Vanderbilt-Ingram Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03054038
- Sponsor's protocol ID
- VICC THO 1684
- Other IDs
- NCI-2016-01532
- Status last verified
- Apr 2022
- First submitted
- 25 Oct 2016
- Last updated
- 14 Apr 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial of Combination Afatinib and Necitumumab in EGFR Mutation Positive NSCLC With Acquired Resistance to First or Third Generation EGFR TKIs
- ClinicalTrials.gov ID
- NCT03054038
- Acronym / sponsor ID
- VICC THO 1684
- Conditions
- Non-Small Cell Lung Carcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low accrual
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Vanderbilt-Ingram Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), National Comprehensive Cancer Network
- Study start
- 20 Jul 2017 (actual)
- Primary completion
- 23 Mar 2022 (actual)
- Study completion
- 23 Mar 2022 (actual)
- First posted
- 15 Feb 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVES:
- To determine the maximum tolerated dose of combination afatinib and necitumumab therapy in EGFR mutation positive non-small cell lung cancer (NSCLC) patients who have progressed following first- and third-generation EGFR tyrosine kinase inhibitors (TKIs).
II. To determine the efficacy and safety profile of afatinib and necitumumab combination therapy in patients with EGFR mutation positive NSCLC patients who have progressed following first- and third-generation EGFR TKIs.
OUTLINE: This is a dose-escalation study.
Patients receive afatinib orally (PO) once daily (QD) on days 1-28 and necitumumab intravenously (IV) over 60 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 28 days and then every 3 months for up to 1 year.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental | Experimental | Drug: Afatinib, Biological: Necitumumab, Other: Laboratory Biomarker AnalysisPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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)
Key exclusion criteria (22 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AfatinibGiven by mouth | Drug | Experimental |
| NecitumumabGiven IV | Biological | Experimental |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Experimental |
Primary outcome
Maximum tolerated dose experience a dose-limiting toxicity
Time frame: Up to 28 days
Highest dosage at which 0 or 1/6 patients
5 secondary outcomes
Objective response rate
Time frame: Up to one year
Objective response rate
Time frame: Up to one year
Overall survival
Time frame: 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
Time frame: Up to 1 year
Incidence of adverse events
Time frame: Up to 1 year
Results and safety
The study was stopped early (reason given: Low accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2022.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sally York, M.D. principal investigator
Vanderbilt-Ingram Cancer Center
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Afatinib, Necitumumab and Laboratory Biomarker Analysis in people with Non-Small Cell Lung Carcinoma, run by Vanderbilt-Ingram Cancer Center at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 14 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Low accrual). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose experience a dose-limiting toxicity (time frame: Up to 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Apr 2022.