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Erlotinib and Momelotinib for the Treatment of Epidermal Growth Factor Receptor (EGFR) Mutated EGFR Tyrosine Kinase Inhibitor (TKI) Naive Metastatic Non-Small Cell Lung Cancer (NSCLC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02206763
Recruitment Status : Terminated
First Posted : August 1, 2014
Last Update Posted : February 1, 2019
Sponsor:
Information provided by (Responsible Party):
Sierra Oncology, Inc.

Brief Summary:
This study will evaluate the safety, preliminary efficacy, and pharmacokinetics (PK) of momelotinib (MMB) and erlotinib, as well as define the maximum tolerated dose (MTD) of momelotinib (MMB) combined with erlotinib in adults with epidermal growth factor receptor (EGFR)-mutated, EGFR tyrosine kinase inhibitor (TKI) naive metastatic non-small cell lung cancer (NSCLC). Participants will be sequentially enrolled to receive progressively increasing doses of momelotinib (MMB) in combination with erlotinib. Escalation of momelotinib (MMB) doses will proceed to the MTD, defined as the highest tested dose associated with dose-limiting toxicities (DLT) during the first 28 days of combined erlotinib and momelotinib (MMB) treatment. There will be four dose levels and each treatment cycle will consist of 28 days.

Condition or disease Intervention/treatment Phase
EGFR Mutated EGFR TKI Naive Metastatic NSCLC Drug: Momelotinib (MMB) Drug: Erlotinib Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 11 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b Study of Erlotinib and Momelotinib for the Treatment of Epidermal Growth Factor Receptor (EGFR) Mutated EGFR Tyrosine Kinase Inhibitor (TKI) Naïve Metastatic Non-Small Cell Lung Cancer (NSCLC)
Actual Study Start Date : October 16, 2014
Actual Primary Completion Date : January 12, 2017
Actual Study Completion Date : February 16, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Momelotinib (MMB)+erlotinib
Participants will receive momelotinib (MMB) plus erlotinib.
Drug: Momelotinib (MMB)
Tablet(s) administered orally once or twice daily
Other Names:
  • GS-0387
  • CYT387

Drug: Erlotinib
Tablet(s) administered orally once daily.
Other Name: Tarceva®




Primary Outcome Measures :
  1. Incidence of Dose Limiting Toxicities (DLTs) [ Time Frame: Up to 28 days ]
    Dose limiting toxicities refer to toxicities experienced during the first 28 days of combined erlotinib and momelotinib (MMB) treatment that have been judged to be clinically significant and related to study treatment.

  2. Safety as Assessed by the Incidence of Adverse Events (AEs) [ Time Frame: Up to 2 years plus 30 days ]
  3. Safety as Assessed by the Percentage of Participants Experiencing Treatment-Emergent Graded Lab Abnormalities (including Chemistry, Coagulation, Hematology, and Urinalysis) [ Time Frame: Up to 2 years plus 30 days ]
  4. Change from Baseline in Vital Signs [ Time Frame: Up to 2 years ]

Secondary Outcome Measures :
  1. Progression-Free Survival [ Time Frame: Until disease progression (up to 2 years) ]
    Progression-free survival is defined as the interval from first dose date of study drug (MMB/erlotinib) to the earlier of the first documentation of definitive disease progression or death from any cause; definitive disease progression is progression based on RECIST criteria v1.1.

  2. Overall Survival [ Time Frame: Until disease progression (up to 2 years) ]
    Overall survival is defined as the interval from first dose date of study drug (MMB/erlotinib) to death from any cause.

  3. Overall Response Rate [ Time Frame: Until disease progression (up to 2 years) ]
    Overall response rate is defined as the proportion of participants who achieve a complete response or partial response.

  4. Pharmacokinetic (PK) Parameter: Cmax of momelotinib (MMB) [ Time Frame: Predose and up to 24 hours postdose ]
    Cmax is defined as the maximum observed concentration of drug.

  5. PK Parameter: AUCtau of momelotinib (MMB) [ Time Frame: Predose and up to 24 hours postdose ]
    AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

  6. PK Parameter: Cmax of Erlotinib [ Time Frame: Predose and up to 24 hours postdose ]
    Cmax is defined as the maximum observed concentration of drug.

  7. PK Parameter: AUCtau of Erlotinib [ Time Frame: Predose and up to 24 hours postdose ]
    AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).



Information from the National Library of Medicine

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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

Key Inclusion Criteria:

  • Metastatic NSCLC with documented EGFR exon 19 deletion or exon 21 (L858R) substitution mutation
  • Treatment naive OR one prior standard chemotherapy that is platinum-based
  • Adequate organ function defined as follows:

    • Hepatic: Total bilirubin < upper limit of the normal range (ULN); aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x ULN
    • Hematological: absolute neutrophil count (ANC) ≥1500 cells/mm^3, platelet ≥ 100,000 cells/mm^3, hemoglobin ≥ 9.0 g/dL
    • Renal: Serum creatinine < ULN OR calculated creatinine clearance (CLcr) of ≥ 60 ml/min
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2

Key Exclusion Criteria:

  • Known positive status for human immunodeficiency virus (HIV)
  • Chronic active or acute viral hepatitis A, B, or C infection (testing required for hepatitis B and C)
  • Presence of > Grade 1 peripheral neuropathy
  • Symptomatic leptomeningeal, brain metastases, or spinal cord compression.
  • History of interstitial pneumonitis

Note: Other protocol defined Inclusion/Exclusion criteria may apply.


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): NCT02206763


Locations
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United States, California
Duarte, California, United States
Palo Alto, California, United States
Whittier, California, United States
Sponsors and Collaborators
Sierra Oncology, Inc.
Investigators
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Study Director: Gilead Study Director Gilead Sciences
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Responsible Party: Sierra Oncology, Inc.
ClinicalTrials.gov Identifier: NCT02206763    
Other Study ID Numbers: GS-US-370-1298
First Posted: August 1, 2014    Key Record Dates
Last Update Posted: February 1, 2019
Last Verified: January 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Erlotinib Hydrochloride
N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action