Recurrent Non-Small Cell Lung CarcinomaPhase 1NCT02451865
Binimetinib With Docetaxel in Treating Patients With Previously Treated, Stage IV Non-small Cell Lung Cancer
A Phase 1 study testing Binimetinib, Docetaxel and Laboratory Biomarker Analysis in people with Recurrent Non-Small Cell Lung Carcinoma and Stage IV Non-Small Cell Lung Cancer, run by Jonsson Comprehensive Cancer Center at 1 site in United States.
Trial summary
This phase Ib trial studies the safety and best dose of binimetinib when given in combination with docetaxel in treating patients with previously treated, stage IV non-small cell lung cancer. Binimetinib and docetaxel may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Non-Small Cell Lung Carcinoma, Stage IV Non-Small Cell Lung Cancer
- What is being tested?
- Binimetinib, Docetaxel and Laboratory Biomarker Analysis
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2016to Jun 2019
- 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 written informed consent
- A histologically or cytologically confirmed diagnosis of stage IV NSCLC
- Must have progressed on at least one prior line of platinum-based therapy for stage IV NSCLC (excluding docetaxel or mitogen activated protein kinase kinase [MEK] inhibitors)
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Measurable disease defined by RECIST criteria
- Ability to provide adequate tissue from archival tumor specimen; confirmation of adequate tissue is required prior to enrollment
Show all 17Show fewer
- In expansion cohort only: patient's kirsten rat sarcoma viral oncogene homolog (KRAS) mutational status must be known prior to enrollment
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
- Hemoglobin (Hgb) >= 9 g/dL without transfusions
- Platelets (PLT) >= 100 x 10^9/L without transfusions
- Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =< 1.5 x upper limit of normal (ULN)
- Total bilirubin =< 1.5 x ULN
- Creatinine =< 1.5 mg/dL
- Left ventricular ejection fraction (LVEF) >= 45% as determined by a multigated acquisition (MUGA) scan or echocardiogram, and QTc interval =< 480ms
- Able to take and retain oral medications
- Patient is deemed by the investigator to have the initiative and means to be compliant with the protocol (treatment and follow-up)
- Negative serum beta-human chorionic gonadotropin (HCG) test (female patient of childbearing potential only) performed locally within 72 hours (hrs) prior to first dose
Who cannot join
- History or current evidence of retinal vein occlusion (RVO) or current risk factors to RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes)
- History of Gilbert syndrome
- Previous or concurrent malignancy within the last 3 years with the exception of adequately treated skin basal or squamous cell with adequate wound healing
- Prior therapy with a MEK-inhibitor or docetaxel for metastatic non-small cell lung cancer (docetaxel in the adjuvant setting will be allowed)
- Epidermal growth factor receptor (EGFR) mutant and/or anaplastic lymphoma receptor tyrosine kinase (ALK) gene rearranged tumor
- Impaired cardiovascular function or clinically significant cardiovascular diseases, including any of the following within 6 months of enrollment: myocardial infarction, unstable angina, coronary artery bypass graft (CABG), coronary angioplasty, or stenting, symptomatic chronic heart failure, clinically significant cardiac arrhythmias and/or conduction (except atrial fibrillation and paroxysmal supraventricular tachycardia)
Show all 21Show fewer
- Uncontrolled arterial hypertension despite appropriate medical therapy
- Known positive serology for human immunodeficiency virus (HIV), active hepatitis B, and/or active hepatitis C infection
- Neuromuscular disorders that are associated with elevated creatine kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy)
- Subjects planning on embarking on a new strenuous exercise regimen after first dose of study treatment that can result in significant increases in plasma CK levels
- Impairment of gastrointestinal function or gastrointestinal disease (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption)
- Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to concerns regarding safety or compliance with clinical study procedures
- Patients who have undergone major surgery =< 3 weeks prior to starting study drug or who have not recovered from side effects of such procedure
- Pregnant or lactating women
- Women of child-bearing potential defined as all women physiologically capable of becoming pregnant who are unwilling to use highly effective methods of contraception throughout the study and 15 days after study drug discontinuation
- Sexually active males unless they are willing to use a condom during intercourse while taking the drug and for 15 days after stopping treatment and are willing to forego fathering a child in this period; a condom is required to be used also by vasectomized men
- Medical, psychiatric, cognitive or other conditions that may compromise the patient's ability to understand the patient information, give informed consent, comply with the study protocol or complete the study
- Grade II or greater neuropathy at baseline
- Symptomatic brain metastases (if a patient has brain metastases and is on steroids, the steroid dose must have been stable for at least 14 days) or brain metastases that have not been previously treated
- Treatment with prior chemotherapy, monoclonal antibodies, other protein or peptide therapeutics or anticancer immunotherapy within 21 days of the first dose of study drug
- Treatment with prior radiotherapy within 28 days of initiating study drug; however, if the radiation portal covered =< 10% of the bone marrow reserve, the patient may be enrolled without respect to the end date of radiotherapy
Trial locations and contacts
1 site in 1 country.
United States1 site
UCLA / Jonsson Comprehensive Cancer Center
Los Angeles, California, 90095
About this study
Official title: A Phase IB Dose Escalation and Expansion Trial of MEK 162 With Docetaxel in Previously Treated Stage IV, Non-small Cell Lung Cancer (NSCLC)
This phase Ib trial studies the safety and best dose of binimetinib when given in combination with docetaxel in treating patients with previously treated, stage IV non-small cell lung cancer. Binimetinib and docetaxel may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Read the detailed description
PRIMARY OBJECTIVES:
- Evaluate the safety and tolerability of increasing doses of MEK162 (binimetinib) with docetaxel 75 mg/m2 every 21 days in patients with stage IV non-small cell lung cancer (NSCLC) that have progressed after at least one prior systemic therapy.
SECONDARY OBJECTIVES:
- Determine objective tumor response rate (RR) as defined by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 with MEK162 and standard doses of docetaxel in stage IV NSCLC.
II. Determine progression free survival (PFS) of MEK162 and standard doses of docetaxel.
III. Evaluate the pharmacokinetic profile of MEK162 when given along with docetaxel.
TERTIARY OBJECTIVES:
- Evaluate tissue biomarkers in baseline tumors and at the time of progression to correlate with clinical outcome II. Assess the activation status of extracellular signal-regulated kinase (ERK), protein kinase B (Akt) and ribosomal protein S6 kinase (S6K) in tumor biopsy samples at baseline and at the time of progression.
III. Determine the cytokine profile before and after treatment in patients.
OUTLINE: This is a dose-escalation study of binimetinib.
Patients receive binimetinib orally (PO) twice daily (BID) on days 1-21 and docetaxel intravenously (IV) on day 21. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who have stable disease or better after completing 6 courses of binimetinib and docetaxel may continue receiving binimetinib PO BID in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then annually for up to 5 years.
- Being tested
- Binimetinib, Docetaxel, 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.
BinimetinibDrug
Also called ARRY-162, ARRY-438162, MEK162
Given PO
DocetaxelDrug
Also called RP56976, Taxotere, Taxotere Injection Concentrate
Given IV
Laboratory Biomarker AnalysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (binimetinib and docetaxel) | Experimental | Patients receive binimetinib PO BID on days 1-21 and docetaxel IV on day 21. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who have stable disease or better after completing 6 courses of binimetinib and docetaxel may continue receiving binimetinib PO BID in the absence of disease progression or unacceptable toxicity. Receives: Drug: Binimetinib; Drug: Docetaxel; Other: Laboratory Biomarker Analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events, graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.03
Side effects will be tabulated according to grade and will do sub-analysis based on patient demographic categories such as age and ECOG performance status.
Measured: Up to 30 days post-treatment
Incidence of dose-limiting toxicities, graded according to the CTCAE v4.03
Side effects will be tabulated according to grade and will do sub-analysis based on patient demographic categories such as age and ECOG performance status.
Measured: 21 days
Maximum tolerated dose of binimetinib in combination with docetaxel
Measured: 21 days
Secondary outcomes (5)
Biomarker analyses
Will determine if there is a correlation of baseline biomarkers and objective tumor response. For categorical markers will use Fisher's exact test to examine the relationship with response and different categorical variables at specific time points. For quantitative markers will use one-way analysis of variance to compare the marker levels between response categories. Correlations between pairs of quantitative markers will be performed using Pearson correlations if the marker distributions are approximately normal. For non-normality will use the Kendall correlation coefficients.
Measured: Up to 30 days post-treatment
Mutations in KRAS and NRAS
Will determine if there is a correlation of response in patients treated with docetaxel and binimetinib with mutations in KRAS and NRAS.
Measured: Up to 30 days post-treatment
Objective tumor response rate (the rate of complete response or partial response), as defined by RECIST 1.1
The proportion ever achieving a clinical and objective tumor response will be estimated and will construct an exact one-sided 90% confidence interval to identify the likely range for the underlying tumor response rate. Tumor response will be correlated with biomarkers as well as other patient characteristics such as ECOG performance status, k-ras and neuroblastoma RAS viral oncogene homolog (n-ras) mutational status using a variety of analytic techniques.
Measured: Up to 5 years
Pharmacokinetic (PK) profile will assess binimetinib (MEK162) levels during treatment cycles
Analyzed by tabulation of PK values with mean and standard deviation at each time point.
Measured: On days 1 and 8 of course 1 and on day 1 of course 2
Progression free survival
Cox-proportional hazards regression models will be used to correlate time to disease progression to both quantitative and categorical variables. Survival distributions will be estimated with the Kaplan-Meier method and significant differences between survival rates will be calculated with the log-rank test.
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 May 2015 (estimated)
- Study startJun 2016
- Primary completionJun 2018 (estimated)
- Study completionJun 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent Non-Small Cell Lung CarcinomaStudies of the same condition, open and under way.
- More trials run by Jonsson Comprehensive Cancer CenterThe sponsor's other registered studies.
- 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
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jonsson Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Edward Garon, Principal investigator, UCLA / Jonsson Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02451865
- Sponsor's protocol ID
- 14-001595
- Other IDs
- NCI-2015-00618, Garon MEK162 NSCLC, 14-001595
- Status last verified
- Jul 2016
- First submitted
- 20 May 2015
- Last updated
- 24 Jul 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IB Dose Escalation and Expansion Trial of MEK 162 With Docetaxel in Previously Treated Stage IV, Non-small Cell Lung Cancer (NSCLC)
- ClinicalTrials.gov ID
- NCT02451865
- Acronym / sponsor ID
- 14-001595
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Jonsson Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Study start
- Jun 2016
- Primary completion
- Jun 2018 (estimated)
- Study completion
- Jun 2019 (estimated)
- First posted
- 22 May 2015 (estimated)
- 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 Ib trial studies the safety and best dose of binimetinib when given in combination with docetaxel in treating patients with previously treated, stage IV non-small cell lung cancer. Binimetinib and docetaxel may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed description
PRIMARY OBJECTIVES:
- Evaluate the safety and tolerability of increasing doses of MEK162 (binimetinib) with docetaxel 75 mg/m2 every 21 days in patients with stage IV non-small cell lung cancer (NSCLC) that have progressed after at least one prior systemic therapy.
SECONDARY OBJECTIVES:
- Determine objective tumor response rate (RR) as defined by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 with MEK162 and standard doses of docetaxel in stage IV NSCLC.
II. Determine progression free survival (PFS) of MEK162 and standard doses of docetaxel.
III. Evaluate the pharmacokinetic profile of MEK162 when given along with docetaxel.
TERTIARY OBJECTIVES:
- Evaluate tissue biomarkers in baseline tumors and at the time of progression to correlate with clinical outcome II. Assess the activation status of extracellular signal-regulated kinase (ERK), protein kinase B (Akt) and ribosomal protein S6 kinase (S6K) in tumor biopsy samples at baseline and at the time of progression.
III. Determine the cytokine profile before and after treatment in patients.
OUTLINE: This is a dose-escalation study of binimetinib.
Patients receive binimetinib orally (PO) twice daily (BID) on days 1-21 and docetaxel intravenously (IV) on day 21. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who have stable disease or better after completing 6 courses of binimetinib and docetaxel may continue receiving binimetinib PO BID in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then annually for up to 5 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (binimetinib and docetaxel) | Experimental | Drug: Binimetinib, Drug: Docetaxel, Other: Laboratory Biomarker AnalysisPatients receive binimetinib PO BID on days 1-21 and docetaxel IV on day 21. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who have stable disease or better after completing 6 courses of binimetinib and docetaxel may continue receiving binimetinib PO BID 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 (17 listed)
- Signed written informed consent
- A histologically or cytologically confirmed diagnosis of stage IV NSCLC
- Must have progressed on at least one prior line of platinum-based therapy for stage IV NSCLC (excluding docetaxel or mitogen activated protein kinase kinase [MEK] inhibitors)
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Measurable disease defined by RECIST criteria
Key exclusion criteria (21 listed)
- History or current evidence of retinal vein occlusion (RVO) or current risk factors to RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes)
- History of Gilbert syndrome
- Previous or concurrent malignancy within the last 3 years with the exception of adequately treated skin basal or squamous cell with adequate wound healing
- Prior therapy with a MEK-inhibitor or docetaxel for metastatic non-small cell lung cancer (docetaxel in the adjuvant setting will be allowed)
- Epidermal growth factor receptor (EGFR) mutant and/or anaplastic lymphoma receptor tyrosine kinase (ALK) gene rearranged tumor
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 |
|---|---|---|
| BinimetinibAlso: ARRY-162, ARRY-438162, MEK162Given PO | Drug | Treatment (binimetinib and docetaxel) |
| DocetaxelAlso: RP56976, Taxotere, Taxotere Injection ConcentrateGiven IV | Drug | Treatment (binimetinib and docetaxel) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (binimetinib and docetaxel) |
Primary outcome
Incidence of adverse events, graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.03
Time frame: Up to 30 days post-treatment
Side effects will be tabulated according to grade and will do sub-analysis based on patient demographic categories such as age and ECOG performance status.
Incidence of dose-limiting toxicities, graded according to the CTCAE v4.03
Time frame: 21 days
Side effects will be tabulated according to grade and will do sub-analysis based on patient demographic categories such as age and ECOG performance status.
Maximum tolerated dose of binimetinib in combination with docetaxel
Time frame: 21 days
5 secondary outcomes
Biomarker analyses
Time frame: Up to 30 days post-treatment
Mutations in KRAS and NRAS
Time frame: Up to 30 days post-treatment
Objective tumor response rate (the rate of complete response or partial response), as defined by RECIST 1.1
Time frame: Up to 5 years
Pharmacokinetic (PK) profile will assess binimetinib (MEK162) levels during treatment cycles
Time frame: On days 1 and 8 of course 1 and on day 1 of course 2
Progression free survival
Time frame: Up to 5 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2020.
Related trials for Recurrent Non-Small Cell Lung Carcinoma
RecruitingObservational study
A Prospective ,Multicenter ,Non-interventional ,Real-world Study Observing Changes in Molecular Markers Osimertinib Targeted Therapy in EGFRm NSCLC
Non Small Cell Lung Cancer
RecruitingObservational study
Patient-Specific MRD Liquid Biopsy in Resected NSCLC: Plasma and Bronchial Washing ctDNA
Non-Small Cell Lung Cancer, Minimal Residual Disease
RecruitingPhase 3
Testing the Impact of an Anti-Cancer Drug, Atezolizumab, After Surgery to Prevent Early Stage Non-small Cell Lung Cancer From Returning, AASI-NSCLC Trial
Lung Non-Small Cell Carcinoma
RecruitingPhase 3
Osimertinib With or Without Bevacizumab as Initial Treatment for Patients With EGFR-Mutant Lung Cancer
Advanced Lung Non-Squamous Non-Small Cell Carcinoma, Metastatic Lung Non-Squamous Non-Small Cell Carcinoma
RecruitingPhase 1
A Study of LY4052031 in Participants With Advanced or Metastatic Urothelial Cancer or Other Solid Tumors
Metastatic Solid Tumor, Recurrent Solid Tumor
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.
Edward Garon principal investigator
UCLA / Jonsson Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Binimetinib, Docetaxel and Laboratory Biomarker Analysis in people with Recurrent Non-Small Cell Lung Carcinoma and Stage IV Non-Small Cell Lung Cancer, run by Jonsson Comprehensive Cancer Center at 1 site 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 17 inclusion and 21 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: withdrawn, as of the sponsor's last update on 24 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 withdrawn before enrolling participants, so there are no results.
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?
Incidence of adverse events, graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.03 (time frame: Up to 30 days post-treatment). The study lists 3 primary outcomes in all. 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 24 Jul 2020.