Lung CancerPhase 1NCT01859026
A Phase I/IB Trial of MEK162 in Combination With Erlotinib in NSCLC Harboring KRAS or EGFR Mutation
A Phase 1 study testing MEK162 and Erlotinib in people with Lung Cancer and Non-Small Cell Lung Cancer, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
Trial summary
The main purpose of this study is to find out if the drugs MEK162 and erlotinib (Tarceva) given in combination are safe and have beneficial effects in patients who have NSCLC. The U.S. Food and Drug Administration (FDA) has not approved MEK162 for use to treat NSCLC. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Cancer, Non-Small Cell Lung Cancer
- What is being tested?
- MEK162 and Erlotinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Dec 2013to 22 Aug 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
- Eligible patients will have a histologic or cytologic diagnosis of NSCLC of the advanced stage (IV), with no known curative treatment options.
- Have a tissue or blood proven KRAS or EGFR mutation confirmed in a Clinical Laboratory Improvement Amendments (CLIA)certified lab (only required in the Phase IB expansion cohort).
- For Phase I/Ib enrollment, Patients with a CLIA confirmed EGFR mutation may be treatment naïve. All other patients must have received at least one previous line of therapy. There will be no limits to prior lines of treatment for the Phase 1 portion.
- Eastern Cooperative Oncology Group (ECOG) performance status of either 0 or 1
- There will be no limits to prior lines of treatment.
- At least one measurable site of disease (as defined by Response Evaluation Criteria in Solid Tumors), or other disease specific response assessment criteria, as appropriate (RECIST 1.1).
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- Have discontinued all previous systemic therapies and recovered from side effects due to systemic treatment for more than 14 days prior to starting on treatment.
- Have discontinued all previous biologic therapies and recovered from side effects due to biologic treatment for more than 14 days prior to starting on treatment.
- Have discontinued all previous external beam radiation therapy and recovered from side effects due to radiation therapy for more than 14 days prior to starting on treatment.
- Have archival tissue sample (if available) or be willing to undergo a repeat biopsy (if feasible).
- Negative serum pregnancy test within 72 hours prior to the first study dose in all women of childbearing potential (WOCBP).
- Adequate organ function and lab parameters
- Prior to any screening or invasive procedure, written informed consent must be obtained.
Who cannot join
- Does not have adequate cardiac function
- Patients with documented central nervous system or leptomeningeal metastasis (brain metastasis) at time of study entry. Patients with prior brain metastasis may be considered if they have completed their treatment for brain metastasis, no longer require corticosteroids, and are asymptomatic.
- Any other serious uncontrolled medical disorder or active infection that would impair the patient's ability to receive study treatment
- Prior use of MEK162 or concurrent use of other approved anticancer or investigational agents. Patients treated with prior EGFR TKI therapy (including erlotinib) are allowed to enroll.
- Gastrointestinal disease that precludes absorption
- History or current evidence of central serous retinopathy (CSR) or retinal vein occlusion (RVO)
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- Any ophthalmopathy visible at screening that would be considered a risk factor for CSR or RVO by the ophthalmologist
- History of another malignancy within 2 years, except cured basal cell carcinoma of the skin or excised carcinoma in situ of the cervix
- Patients who have received prior anti-cancer treatment within the following time frames: systemic therapies less than 14 days prior to starting on treatment; radiation therapy less than 14 days prior to starting on treatment; biologic therapy less than 14 days prior to starting on treatment.
- Patients who have not recovered from side effects of prior anti-cancer treatment to less than or equal to grade 1 toxicity according to Common Toxicity Criteria for Adverse Effects (CTCAE) v.4 within the following time frames: Received previous systemic therapy and has not recovered from side effects for more than 14 days prior to starting on treatment; Received previous radiation therapy and has not recovered from side effects for more than 14 days prior to starting on treatment; Received previous biologic therapy and has not recovered from side effects for more than 14 days prior to starting on treatment
- Have undergone major surgery < 4 weeks of initiation of study medication or who have not recovered from side effects of such procedure
- Patients with concurrent uncontrolled medical conditions that may interfere with their participation in the study or potentially affect the interpretation of the study data
- Women who are pregnant or nursing
- Women of child-bearing potential (WOCBP) and males who have not been sterilized by vasectomy or other means with partners who are WOCBP, UNLESS the women are using two birth control methods. The two methods can be a double barrier method or a barrier method plus a hormonal method.
- Unwilling or unable to comply with the protocol
- Known positive serology for HIV, active Hepatitis B, and/or active Hepatitis C infection
- History of Gilbert's syndrome
- Neuromuscular disorders that are associated with elevated creatinine kinase (CK)
- Patients who are planning on embarking on a new strenuous exercise regimen after first dose of study treatment. Muscular activities, such as strenuous exercise, that can result in significant increases in plasma CK levels should be avoided while on MEK162 treatment.
- Previous treatment with any substrate of CYP2B6 enzyme < 14 days prior to initiation of investigational products
Trial locations and contacts
1 site in 1 country.
United States1 site
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612
About this study
Official title: A Phase I/IB Trial of MEK162 in Combination With Erlotinib in Non-Small Cell Lung Cancer (NSCLC) Harboring KRAS or EGFR Mutation
The main purpose of this study is to find out if the drugs MEK162 and erlotinib (Tarceva) given in combination are safe and have beneficial effects in patients who have NSCLC.
The U.S. Food and Drug Administration (FDA) has not approved MEK162 for use to treat NSCLC. Erlotinib is an FDA approved drug for the treatment of Non-Small Cell Lung Cancer.
- Conditions
- Lung Cancer, Non-Small Cell Lung Cancer
- Being tested
- MEK162, Erlotinib
- Keywords
- Epidermal growth factor receptor (EGFR), EGFR mutation, Kirsten rat sarcoma 2 viral oncogene homolog(KRAS), KRAS mutation, Non-Small Cell Lung Cancer (NSCLC), Advanced-stage IV
- Medical subject headings
- Lung Neoplasms, Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MEK162Drug
Also called ARRY-162, ARRY-438162, Mitogen Activated Kinase (MEK) inhibitor
Treatment as outlined in study arms.
ErlotinibDrug
Also called Tarceva, CP-358,774, OSI-774, Reversible tyrosine kinase inhibitor
Treatment as outlined in study arms.
| Study group | Role | What they receive |
|---|---|---|
| Phase I - Dose Escalation | Experimental | For the Phase I portion, patients will start MEK162 by mouth (p.o.) on cycle 1, day 1 and erlotinib on cycle 1, day 2. The MEK162 will be dosed once daily (QD) or twice (b.i.d.), and erlotinib will be dosed daily (QD) on a 28-day cycle.
Phase I will be followed by an expansion Phase Ib. Receives: Drug: MEK162; Drug: Erlotinib |
| Arm A: Dose Expansion | Experimental | Phase Ib Arm A: EGFR Mutant Tumor Status. In the phase IB expansion cohort study there are 2 arms based on the presence of the EGFR (Arm A) or KRAS (Arm B) mutation.
The treatments for each arm are the same: MEK162 (2 time a day) and erlotinib (once) daily on 28 day cycles. Receives: Drug: MEK162; Drug: Erlotinib |
| Arm B: Dose Expansion | Experimental | Phase Ib Arm B: KRAS Mutant Tumor Status. In the phase IB expansion cohort study there are 2 arms based on the presence of the EGFR (Arm A) or KRAS (Arm B) mutation.
The treatments for each arm are the same: MEK162 (2 time a day) and erlotinib (once) daily on 28 day cycles. Receives: Drug: MEK162; Drug: Erlotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I: Maximum Tolerated Dose (MTD)
To evaluate the safety of MEK162 plus erlotinib in patients with advanced NSCLC by evaluating toxicities of therapy and establish a recommended phase IB dosing of MEK162 and erlotinib. Safety population: consists of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.
Measured: 6 months
Secondary outcomes (2)
Number of Participants with Progression Free Survival (PFS)
PFS is defined as the duration of time from the time of randomization to time of disease progression or death, whichever occurs first. Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Measured: 6 months
Number of Participants with Overall Survival (OS)
OS, defined as the time from study enrollment to death from any cause during the study duration.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2013 (estimated)
- Study start30 Dec 2013
- Primary completion22 Aug 2019
- Study completion22 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Lung CancerStudies of the same condition, open and under way.
- More trials run by H. Lee Moffitt Cancer Center and Research InstituteThe 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Array BioPharma
- Responsible party
- Sponsor
- Investigators
- Jhanelle Gray, M.D., Principal investigator, H. Lee Moffitt Cancer Center and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01859026
- Sponsor's protocol ID
- MCC-17361
- Status last verified
- Jan 2023
- First submitted
- 17 May 2013
- Last updated
- 19 Jan 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Saltos AN, Creelan BC, Tanvetyanon T, Chiappori AA, Antonia SJ, Shafique MR, Ugrenovic-Petrovic M, Sansil S, Neuger A, Ozakinci H, Boyle TA, Kim J, Haura EB, Gray JE. A phase I/IB trial of binimetinib in combination with erlotinib in NSCLC harboring activating KRAS or EGFR mutations. Lung Cancer. 2023 Sep;183:107313. doi: 10.1016/j.lungcan.2023.107313. Epub 2023 Jul 22.
PubMed 37499521
Study at a glance
From the registry record, last updated by the sponsor on 19 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/IB Trial of MEK162 in Combination With Erlotinib in Non-Small Cell Lung Cancer (NSCLC) Harboring KRAS or EGFR Mutation
- ClinicalTrials.gov ID
- NCT01859026
- Acronym / sponsor ID
- MCC-17361
- Conditions
- Lung Cancer, Non-Small Cell Lung Cancer
- Keywords
- Epidermal growth factor receptor (EGFR), EGFR mutation, Kirsten rat sarcoma 2 viral oncogene homolog(KRAS), KRAS mutation, Non-Small Cell Lung Cancer (NSCLC), Advanced-stage IV
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Collaborators
- Array BioPharma
- Study start
- 30 Dec 2013 (actual)
- Primary completion
- 22 Aug 2019 (actual)
- Study completion
- 22 Aug 2019 (actual)
- First posted
- 21 May 2013 (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.
The main purpose of this study is to find out if the drugs MEK162 and erlotinib (Tarceva) given in combination are safe and have beneficial effects in patients who have NSCLC.
The U.S. Food and Drug Administration (FDA) has not approved MEK162 for use to treat NSCLC. Erlotinib is an FDA approved drug for the treatment of Non-Small Cell Lung Cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Phase I - Dose Escalation | Experimental | Drug: MEK162, Drug: ErlotinibFor the Phase I portion, patients will start MEK162 by mouth (p.o.) on cycle 1, day 1 and erlotinib on cycle 1, day 2. The MEK162 will be dosed once daily (QD) or twice (b.i.d.), and erlotinib will be dosed daily (QD) on a 28-day cycle. Phase I will be followed by an expansion Phase Ib. |
| Arm A: Dose Expansion | Experimental | Drug: MEK162, Drug: ErlotinibPhase Ib Arm A: EGFR Mutant Tumor Status. In the phase IB expansion cohort study there are 2 arms based on the presence of the EGFR (Arm A) or KRAS (Arm B) mutation. The treatments for each arm are the same: MEK162 (2 time a day) and erlotinib (once) daily on 28 day cycles. |
| Arm B: Dose Expansion | Experimental | Drug: MEK162, Drug: ErlotinibPhase Ib Arm B: KRAS Mutant Tumor Status. In the phase IB expansion cohort study there are 2 arms based on the presence of the EGFR (Arm A) or KRAS (Arm B) mutation. The treatments for each arm are the same: MEK162 (2 time a day) and erlotinib (once) daily on 28 day cycles. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Eligible patients will have a histologic or cytologic diagnosis of NSCLC of the advanced stage (IV), with no known curative treatment options.
- Have a tissue or blood proven KRAS or EGFR mutation confirmed in a Clinical Laboratory Improvement Amendments (CLIA)certified lab (only required in the Phase IB expansion cohort).
- For Phase I/Ib enrollment, Patients with a CLIA confirmed EGFR mutation may be treatment naïve. All other patients must have received at least one previous line of therapy. There will be no limits to prior lines of treatment for the Phase 1 portion.
- Eastern Cooperative Oncology Group (ECOG) performance status of either 0 or 1
- There will be no limits to prior lines of treatment.
Key exclusion criteria (20 listed)
- Does not have adequate cardiac function
- Patients with documented central nervous system or leptomeningeal metastasis (brain metastasis) at time of study entry. Patients with prior brain metastasis may be considered if they have completed their treatment for brain metastasis, no longer require corticosteroids, and are asymptomatic.
- Any other serious uncontrolled medical disorder or active infection that would impair the patient's ability to receive study treatment
- Prior use of MEK162 or concurrent use of other approved anticancer or investigational agents. Patients treated with prior EGFR TKI therapy (including erlotinib) are allowed to enroll.
- Gastrointestinal disease that precludes absorption
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 |
|---|---|---|
| MEK162Also: ARRY-162, ARRY-438162, Mitogen Activated Kinase (MEK) inhibitorTreatment as outlined in study arms. | Drug | Arm A: Dose Expansion, Arm B: Dose Expansion, Phase I - Dose Escalation |
| ErlotinibAlso: Tarceva, CP-358,774, OSI-774, Reversible tyrosine kinase inhibitorTreatment as outlined in study arms. | Drug | Arm A: Dose Expansion, Arm B: Dose Expansion, Phase I - Dose Escalation |
Primary outcome
Phase I: Maximum Tolerated Dose (MTD)
Time frame: 6 months
To evaluate the safety of MEK162 plus erlotinib in patients with advanced NSCLC by evaluating toxicities of therapy and establish a recommended phase IB dosing of MEK162 and erlotinib. Safety population: consists of all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.
2 secondary outcomes
Number of Participants with Progression Free Survival (PFS)
Time frame: 6 months
Number of Participants with Overall Survival (OS)
Time frame: 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jan 2023.
- Derived from this study: PubMed 37499521Saltos AN, Creelan BC, Tanvetyanon T, Chiappori AA, Antonia SJ, Shafique MR, Ugrenovic-Petrovic M, Sansil S, Neuger A, Ozakinci H, Boyle TA, Kim J, Haura EB, Gray JE. A phase I/IB trial of binimetinib in combination with erlotinib in NSCLC harboring activating KRAS or EGFR mutations. Lung Cancer. 2023 Sep;183:107313. doi: 10.1016/j.lungcan.2023.107313. Epub 2023 Jul 22.
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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.
Jhanelle Gray, M.D. principal investigator
H. Lee Moffitt Cancer Center and Research Institute
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 MEK162 and Erlotinib in people with Lung Cancer and Non-Small Cell Lung Cancer, run by H. Lee Moffitt Cancer Center and Research Institute 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 13 inclusion and 20 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: finished, as of the sponsor's last update on 19 Jan 2023. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Phase I: Maximum Tolerated Dose (MTD) (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01859026, which also lists 1 linked publication.
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 19 Jan 2023.