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A Phase I/IB Trial of MEK162 in Combination With Erlotinib in NSCLC Harboring KRAS or EGFR Mutation

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ClinicalTrials.gov Identifier: NCT01859026
Recruitment Status : Recruiting
First Posted : May 21, 2013
Last Update Posted : October 3, 2018
Sponsor:
Collaborator:
Array BioPharma
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute

Brief 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. Erlotinib is an FDA approved drug for the treatment of Non-Small Cell Lung Cancer.


Condition or disease Intervention/treatment Phase
Lung Cancer Non-Small Cell Lung Cancer Drug: MEK162 Drug: Erlotinib Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 44 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : December 10, 2013
Estimated Primary Completion Date : March 31, 2019
Estimated Study Completion Date : March 31, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: Phase I - Dose Escalation

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.

Drug: MEK162
Treatment as outlined in study arms.
Other Names:
  • ARRY-162
  • ARRY-438162
  • Mitogen Activated Kinase (MEK) inhibitor

Drug: Erlotinib
Treatment as outlined in study arms.
Other Names:
  • Tarceva
  • CP-358,774
  • OSI-774
  • Reversible tyrosine kinase inhibitor
  • Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor

Experimental: Arm A: Dose Expansion

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.

Drug: MEK162
Treatment as outlined in study arms.
Other Names:
  • ARRY-162
  • ARRY-438162
  • Mitogen Activated Kinase (MEK) inhibitor

Drug: Erlotinib
Treatment as outlined in study arms.
Other Names:
  • Tarceva
  • CP-358,774
  • OSI-774
  • Reversible tyrosine kinase inhibitor
  • Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor

Experimental: Arm B: Dose Expansion

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.

Drug: MEK162
Treatment as outlined in study arms.
Other Names:
  • ARRY-162
  • ARRY-438162
  • Mitogen Activated Kinase (MEK) inhibitor

Drug: Erlotinib
Treatment as outlined in study arms.
Other Names:
  • Tarceva
  • CP-358,774
  • OSI-774
  • Reversible tyrosine kinase inhibitor
  • Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Number of Participants with Progression Free Survival (PFS) [ Time Frame: 6 months ]
    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).

  2. Number of Participants with Overall Survival (OS) [ Time Frame: 3 years ]
    OS, defined as the time from study enrollment to death from any cause during the study duration.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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).
  • 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.

Exclusion Criteria:

  • 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)
  • 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

Information from the National Library of Medicine

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): NCT01859026


Locations
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute Recruiting
Tampa, Florida, United States, 33612
Contact: Germaine Gonzalez-Vazquez    813-745-6636    germaine.gonzalezvazquez@moffitt.org   
Sub-Investigator: Scott Antonia, M.D.         
Sub-Investigator: Eric Haura, M.D.         
Sub-Investigator: Charles Williams, M.D.         
Principal Investigator: Jhanelle Gray, M.D.         
Sub-Investigator: Tawee Tanvetyanon, M.D.         
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Array BioPharma
Investigators
Principal Investigator: Jhanelle Gray, M.D. H. Lee Moffitt Cancer Center and Research Institute

Additional Information:
Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT01859026     History of Changes
Other Study ID Numbers: MCC-17361
First Posted: May 21, 2013    Key Record Dates
Last Update Posted: October 3, 2018
Last Verified: October 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
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

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Erlotinib Hydrochloride
Mitogens
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Mitosis Modulators