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Trial record 1 of 1 for:    NCT02864992
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Tepotinib Phase II Study in Lung Adenocarcinoma Harbouring MET Exon 14 (METex14) Skipping Alterations

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2017 by EMD Serono
Sponsor:
Collaborator:
Merck KGaA
Information provided by (Responsible Party):
EMD Serono ( EMD Serono Research & Development Institute, Inc. )
ClinicalTrials.gov Identifier:
NCT02864992
First received: July 29, 2016
Last updated: February 27, 2017
Last verified: February 2017
  Purpose
This study will look at how effective the study drug (tepotinib) is at stopping the growth and spread of lung cancer that carries a specific genetic alteration (MET exon 14 skipping alterations) and that did not respond to standard of care treatment such as chemotherapy (platinum doublet containing regimen). This study will also measure a number of other things including safety of the study drug and the side effects, how body processes the study drug, or how the study drug affects your quality of life. The study also has an optional pharmacogenetic research part. Pharmacogenetic research is an important way to try to understand the role of genetics in human disease and how genes impact the effectiveness of drugs, because differences in genes can change the way a person responds to a particular drug

Condition Intervention Phase
Lung Adenocarcinoma Stage IIIB/IV
Drug: tepotinib
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase II Single-arm Trial to Investigate Tepotinib in Stage IIIB/IV Adenocarcinoma of the Lung With MET Exon 14 (METex14) Skipping Alterations After Failure of at Least One Prior Active Therapy, Including a Platinum-doublet-containing Regimen

Resource links provided by NLM:


Further study details as provided by EMD Serono:

Primary Outcome Measures:
  • Objective response as assessed by independent review committee [ Time Frame: Baseline up to 20 months ]
    Objective response will be determined according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and as adjudicated by an Independent review committee. Objective response is defined as either a confirmed complete response (CR) or partial response (PR) from first administration of trial treatment to first observation of progressive disease (PD). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD is defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.


Secondary Outcome Measures:
  • Objective response assessed as per Investigator [ Time Frame: Baseline up to 20 months ]
    Objective response will be determined according to RECIST 1.1 and as per investigator's discretion. Objective response is defined as either a confirmed complete response (CR) or partial response (PR) from first administration of trial treatment to first observation of progressive disease (PD) .CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD is defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.

  • Duration of response as assessed by independent review committee [ Time Frame: Baseline until PD/ death within 84 days of last tumor assessment; assessed up to 20 months ]
    Duration of response according to RECIST 1.1 and as adjudicated by an Independent review committee is the time from when the CR/PR (whichever is first) criteria are first met until progression of disease (PD) or death due to any cause within 84 days of the last tumor assessment, whichever occurs first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD is defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.

  • Duration of response as assessed by investigator [ Time Frame: Baseline until PD/ death within 84 days of last tumor assessment; assessed up to 20 months ]
    Duration of response according to RECIST 1.1 and as per investigator's discretion is the time from when the CR/PR (whichever is first) criteria are first met until progression of disease (PD) or death due to any cause within 84 days of the last tumor assessment, whichever occurs first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD is defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.

  • Objective disease control as assessed by independent review committee [ Time Frame: Baseline up to 20 months ]
    Objective disease control will be determined according to RECIST 1.1 and as adjudicated by an Independent review committee. Objective disease control is defined as either a confirmed CR or PR, or stable disease (SD) lasting at least 12 weeks (84 days) as assessed by independent review committee. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Stable disease (SD)=Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD is defined as at least a 20 % increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.

  • Objective disease control as assessed by investigator [ Time Frame: Baseline up to 20 months ]
    Objective disease control will be determined according to RECIST 1.1 and as per investigator's discretion. Objective disease control is defined as either a confirmed CR or PR, or stable disease (SD) lasting at least 12 weeks (84 days) as assessed by investigator. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Stable disease (SD)=Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD is defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.

  • Progression free survival as assessed by independent review committee [ Time Frame: Baseline until PD or death within 84 days of last tumor assessment; assessed up to 20 months ]
    Progression free survival as assessed by independent review committee is defined as the time (in months) from the first administration of trial treatment to the date of the first documentation of PD (based on independent review) or death due to any cause within 84 days of the last tumor assessment, whichever occurs first. PD is defined as at least a 20 % increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.

  • Progression free survival as assessed by investigator [ Time Frame: Baseline until PD or death within 84 days of last tumor assessment; assessed up to 20 months ]
    Progression free survival as assessed by investigator is defined as the time (in months) from the first administration of trial treatment to the date of the first documentation of PD (as assessed by investigator) or death due to any cause within 84 days of the last tumor assessment, whichever occurs first. PD is defined as at least a 20 % increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.

  • Overall survival [ Time Frame: Baseline until death, assessed up to 20 months ]
    Overall survival is defined as the time (in months) from first trial treatment administration to the date of death.

  • Occurrence of Treatment emergent adverse event (TEAEs) and deaths [ Time Frame: From the first dose of study drug administration until 33 days after the last dose of study drug administration, assessed up to 20 Months ]
    This outcome measure will be presented as the percentage of subjects with any (serious) adverse event (AE). Percentages are calculated using total number of subjects per treatment cohort as the denominator.

  • Percentage of subjects with of markedly abnormal clinical laboratory tests (hematology and coagulation, biochemistry and urinalysis), vital signs, Electrocardiogram (ECG), and Eastern Cooperative Oncology Group Performance Status (ECOG PS) [ Time Frame: Baseline up to 20 months ]
    This outcome measure will be presented as the percentage of subjects with markedly abnormal vital sign measurements. Percentages are calculated using total number of subjects per treatment cohort as the denominator. Abnormalities in Systolic blood pressure, diastolic blood pressure, pulse rate, respiratory rate, body temperature as a part of vital signs; electrocardiogram (ECG) wave, body weight, and Eastern Cooperative Oncology Group (ECOG) Performance Status (PS), and clinical laboratory tests (hematology and coagulation, biochemistry and urinalysis) will be assessed.

  • European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) [ Time Frame: Baseline up to 20 months ]
  • European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13) [ Time Frame: Baseline up to 20 months ]
  • EuroQol Five Dimension Five Level Scale (EQ5D5L) [ Time Frame: Baseline up to 20 months ]
  • Maximum Plasma concentration (Cmax) of drug [ Time Frame: pre-dose, at 1.5 hours post-dose and at 4 hours post-dose on Cycle 1, Day 1 and on Cycle 2, Day 1 ]
  • Trough plasma concentration (Ctrough) of drug [ Time Frame: pre-dose, at 1.5 hours post-dose and at 4 hours post-dose on Cycle 1, Day 1 and on Cycle 2, Day 1 ]
  • Number of subjects with markedly abnormal clinical laboratory tests (hematology and coagulation, biochemistry and urinalysis). [ Time Frame: Baseline up to 20 months ]

Estimated Enrollment: 60
Study Start Date: September 2016
Estimated Study Completion Date: September 2018
Estimated Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: tepotinib Drug: tepotinib
Subjects received 500 mg of tepotinib tablet once daily orally during each 21 day cycle until disease progression, adverse event or withdrawal by the subject.

  Eligibility

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

Inclusion Criteria:

  • Histologically confirmed advanced adenocarcinoma of the lung, having failed at least one bot not more than 2 lines of systemic therapy, including a platinum-doublet-containing regimen, but having failed a maximum of 2 lines of active therapy
  • MET Exon 14 (METex14) skipping alterations, as determined by the central laboratory. Both, archival and fresh biopsies are acceptable; In case METex14 skipping alteration has been observed in a subject in a pre-trial setting, it should be ensured that sufficient tissue is available for re-testing before trial entry. Only subjects with METex14 skipping mutation based on trial central testing will be enrolled into the trial
  • Signed, written informed consent by subject or legal representative prior to any trial-specific screening procedure
  • Male or female, greater than or equal to (>=) 18 years of age (or having reached the age of majority according to local laws and regulations, if the age of majority is > 18 years of age); [i.e. >= 20 years of age in Japan])
  • Measurable disease in accordance with RECIST version 1.1
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
  • A female subjects is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
  • Not a woman of childbearing potential as defined in Appendix VIII OR
  • A woman of childbearing potential who agrees to use a highly effective contraception (i.e., methods with a failure rate of less than 1 % per year) as detailed in in Appendix VII of this protocol 2 weeks before start of first dose of study treatment, during the treatment period and for at least 4 weeks after the last dose of study treatment. Women of childbearing potential must have a negative pregnancy test (β-HCG test in serum) prior to enrollment.
  • A male subject must agree to use and to have their female partners of childbearing potential to use a highly effective contraception (i.e., methods with a failure rate of less than 1 % per year) as detailed in Appendix VII of this protocol from the first dose of study treatment, during the treatment period and for at least 3 months after the last dose of study treatment and refrain from donating sperm during this period. Male subjects should always use a barrier method such as condom concomitantly.

Exclusion Criteria:

  • Subjects with characterized Epidermal Growth Factor Receptor (EGFR) (documented results; local testing acceptable) that predict sensitivity to EGFR-therapy, including, but not limited to exon 19 deletions and exon 21 alterations
  • Subjects with characterized Anaplastic Lymphoma Kinase (ALK) rearrangements (documented results; local testing acceptable)
  • Active brain metastases (defined as neurologically stable for less than (<) 4 weeks and/or symptomatic and/or requiring treatment with steroids and/or leptomeningeal disease) Subjects must have completed any prior treatment for brain metastases >= 4 weeks prior to start of therapy (>= 2 weeks for stereotactic radiosurgery/gamma knife). Subjects who are neurologically stable on symptomatic therapy with anticonvulsants with low drug interaction risk or whose steroids are being tapered are eligible. Asymptomatic untreated brain metastases less than or equal to (<=) 1 cm are eligible
  • Any unresolved toxicity Grade 2 or more according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) from previous anticancer therapy
  • Need for transfusion within 14 days prior to the first dose of trial treatment
  • Prior chemotherapy, biological therapy, radiation therapy, or other investigational anticancer therapy (not including palliative radiotherapy at focal sites) within 21 days prior to the first dose of trial treatment
  • Subjects who have brain metastasis as the only measureable lesion
  • Inadequate hematological, liver, renal, cardiac function
  • Prior treatment with other agents targeting the HGF/c-Met pathway
  • Past or current history of neoplasm other than Non-small Cell Lung Cancer (NSCLC), except for curatively treated non-melanoma skin cancer, in situ carcinoma of the cervix, or other cancer curatively treated and with no evidence of disease for at least 5 years
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02864992

Contacts
Contact: US Medical Information 888-275-7376
Contact: Merck KGaA Communication Center +49 6151 72 5200 service@merckgroup.com

  Show 36 Study Locations
Sponsors and Collaborators
EMD Serono Research & Development Institute, Inc.
Merck KGaA
Investigators
Study Director: Medical Responsible EMD Serono Research & Development Institute, Inc, a business of Merck KGaA, Darmstadt, Germany
  More Information

Responsible Party: EMD Serono Research & Development Institute, Inc.
ClinicalTrials.gov Identifier: NCT02864992     History of Changes
Other Study ID Numbers: MS200095-0022
2015-005696-24 ( EudraCT Number )
Study First Received: July 29, 2016
Last Updated: February 27, 2017

Keywords provided by EMD Serono:
lung
neoplasm
cancer
tumor
adenocarcinoma
MET exon 14
METex14
pulmonary
stage III
stage IV
c-Met
cMET
NSCLC
non-small cell lung cancer

Additional relevant MeSH terms:
Adenocarcinoma
Lung Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on April 28, 2017