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A Phase I/II, Multicenter, Open-label Study of EGFRmut-TKI EGF816, Administered Orally in Adult Patients With EGFRmut Solid Malignancies

This study is currently recruiting participants.
See Contacts and Locations
Verified June 2017 by Novartis ( Novartis Pharmaceuticals )
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT02108964
First received: April 7, 2014
Last updated: June 15, 2017
Last verified: June 2017
  Purpose
To estimate the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) (Phase l part) of EGF816 and to investigate the anti-tumor activity of EGF816 (Phase II part).

Condition Intervention Phase
Advanced Non-small Cell Lung Cancer Drug: EGF816 Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase I/II, Multicenter, Open-label Study of EGFRmut-TKI EGF816, Administered Orally in Adult Patients With EGFRmut Solid Malignancies

Resource links provided by NLM:


Further study details as provided by Novartis ( Novartis Pharmaceuticals ):

Primary Outcome Measures:
  • Incidence of Dose Limiting Toxicity (DLT) Phase I Part [ Time Frame: First 28 days of dosing ]
    Maximum tolerated dose (MTD) or Recommended Phase II dose (RP2D)

  • Overall Response Rate (ORR) Phase II Part [ Time Frame: At least 24 weeks ]
    ORR is defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR) determined by Blinded Independent Review Committee (BIRC) assessment in accordance to Response Evaluation Criteria in Solid Tumors (RECIST 1.1).


Secondary Outcome Measures:
  • Progression-free survival (Phase I & Phase II Parts) [ Time Frame: At least 24 weeks ]
    PFS is defined as time from date of first dose of study treatment to date of first documented disease progression or death due to any cause determined by by Investigator assessment in accordance to RECIST 1.1

  • Duration of Response (Phase I & II Parts) [ Time Frame: At least 24 weeks ]
    DOR is defined as the time from first documented response (PR or CR) to the date of first documented disease progression or death due to any cause determined by Investigator assessment in accordance to RECIST 1.1

  • Plasma concentration vs. time profiles, plasma PK parameters (Phase I Part & Phase II part) [ Time Frame: 12 weeks (Cycle 1 Day 1,2,8, 15; Cycle 2 Day 1, 2; Cycle 3 Day 1; Cycle 4 Day 1 ]
    To characterize the PK properties of EGF816 and metabolite LMI258 (Phase I & II parts)

  • Pre- and on-treatment immunohistochemistry of EGFR pathway molecules (prior to PA05) [ Time Frame: 15 days (Pre-screening, screening and Cycle 1 Day 15) ]
    To assess the tumor EGFR signaling inhibition by EGF816

  • Overall Response Rate (Phase I & II Parts) [ Time Frame: At least 24 weeks ]
    ORR is defined as proportion of patients with best overall response of (PR+CR) determined by Investigator assessment assessment in accordance to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

  • Disease Control Rate (Phase I & II Parts) [ Time Frame: At least 24 weeks ]
    DCR is defined as the proportion of patients with best overall response of CR, PR, or SD determined by Investigator assessment assessment in accordance to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

  • Time to Response (Phase I & II Parts) [ Time Frame: At least 24 weeks ]
    TTR is defined as the time from the date of the first dose to the date of first documented response (CR or PR) determined by Investigator assessment assessment in accordance to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

  • Safety: Incidence and severity of AEs, changes in laboratory values, vital signs & ECGs. Tolerability: Dose interruptions & reductions (Phase I & II Parts) [ Time Frame: At least 24 weeks ]
    Assessment of the safety and tolerability of EGF816 will be performed continuously during the treatment phase and 30 days after discontinuation of the study treatment

  • Duration of Response (Phase II Part) [ Time Frame: At least 24 weeks ]
    DOR is defined as the time from first documented response (PR or CR) to the date of first documented disease progression or death due to any cause determined by Blinded Independent Review Committee in accordance to RECIST 1.1

  • Disease Control Rate (Phase II Part) [ Time Frame: At least 24 weeks ]
    DCR is defined as the proportion of patients with best overall response of CR, PR, or SD determined by Blinded Independent Review Committee (BIRC) in accordance to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

  • Progression-Free Survival (Phase II Part) [ Time Frame: At least 24 weeks ]
    Progression-free survival (PFS). PFS is defined as time from date of first dose of study treatment to date of first documented disease progression or death due to any cause determined by Blinded Independent Review Committee in accordance to RECIST 1.1

  • Time to Response (Phase II Part) [ Time Frame: At least 24 weeks ]
    TTR is defined as as the time from the date of first dose of study treatment to the date of first documented response (CR or PR) determined by Blinded Independent Review Committee (BIRC) in accordance to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

  • Overall Survival (Phase II Part) [ Time Frame: At least 24 weeks ]
    OS is defined as the time from first dose of the study treatment to the date of death due to any cause.


Estimated Enrollment: 220
Actual Study Start Date: June 6, 2014
Estimated Study Completion Date: July 25, 2019
Estimated Primary Completion Date: February 11, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase I part
180 patients with EGFR mutations (Recruitment is completed)
Drug: EGF816
EGF816 will be dosed once daily. On the first day of each treatment Cycle, the patient receives an adequate drug supply for self-administration at home. The investigator must emphasize compliance with the study treatment and will instruct the patient to take EGF816 exactly as prescribed.
Experimental: Phase II part
At least 40 patients who have advanced NSCLC and EGFR activating mutations (i.e. L858R and/or ex19del). These patients must be treatment naïve and must have not received any systemic antineoplastic therapy for advanced NSCLC. Note: patients who have received no more than 1 cycle of antineoplastic therapy in the advanced setting are allowed.
Drug: EGF816
EGF816 will be dosed once daily. On the first day of each treatment Cycle, the patient receives an adequate drug supply for self-administration at home. The investigator must emphasize compliance with the study treatment and will instruct the patient to take EGF816 exactly as prescribed.

  Eligibility

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

Inclusion Criteria: (For all patients unless otherwise specified)

  • Histologically or cytologically confirmed locally advanced (stage IIIB not amenable to definitive multi-modality therapy including surgery) or metastatic (stage IV) EGFR mutant NSCLC.
  • Patients with controlled brain metastases
  • ECOG performance status: Phase I part: 0, 1, or 2; Phase II part: 0 or 1
  • Presence of at least one measurable lesion according to RECIST 1.1
  • Patients who are either HBsAg positive or HBV-DNA positive must be willing and able to take antiviral therapy 1-2 weeks prior to 1st dose of EGF816 treatment and continue on antiviral therapy for at least 4 weeks after the last dose of EGF816
  • Patients must have negative hepatitis C antibody (HCV-Ab) or positive HCV-Ab but undetectable level of HCV-RNA. Note: patients with detectable HCV-RNA are not eligible for the study.
  • For Phase I: patients must have failed no more than 3 lines of any systemic antineoplastic therapy for advanced NSCLC, including EGFR-TKI
  • For Phase II: patients must be naïve from any systemic antineoplastic therapy in the advanced setting. Patients who have failed no more than 1 cycle of systemic antineoplastic therapy in the advanced setting are allowed.

Exclusion criteria: (Applies to all patients unless otherwise specified)

  • Patients with a history or presence of ILD or interstitial pneumonitis, including clinically significant radiation pneumonitis (i.e. affecting activities of daily living or requiring therapeutic intervention)
  • Presence or history of another malignancy
  • Undergone a bone marrow or solid organ transplant
  • Known history of human immunodeficiency virus (HIV) seropositivity (HIV testing is not mandatory)
  • Patients receiving concomitant immunosuppressive agents or chronic corticosteroids use at the time of study entry except for control of brain metastases, topical applications, inhaled sprays, eye drops or local injections
  • Patients with clinically significant, uncontrolled heart disease
  • Any prior therapies ≤ 4 weeks prior to the first dose of study treatment
  • Patients who are receiving treatment with medications that are known to be strong inhibitors or inducers of CYP3A4/5 and cannot be discontinued 1 week prior to the start of EGF816 treatment and for the duration of the study.
  • Patients who have impairment of GI function or GI disease that may significantly alter the absorption of EGF816 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome)
  • Patients who are receiving treatment with any enzyme-inducing anticonvulsant that cannot be discontinued at least 1 week before first dose of study treatment, and for the duration of the study
  • Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception
  • Sexually active males unless they use a condom during intercourse while taking drug and for 3 months after stopping treatment Other protocol-defined inclusion and exclusion criteria may apply.
  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: NCT02108964

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111 novartis.email@novartis.com

Locations
United States, Massachusetts
Massachusetts General Hospital Mass General Recruiting
Boston, Massachusetts, United States, 02114
Contact: Marianela E. Oser    617-724-1223    MOSER@mgh.harvard.edu   
Principal Investigator: Lecia Sequist         
United States, New York
Memorial Sloan Kettering Cancer Center Oncology Department Recruiting
New York, New York, United States, 10065
Contact: Murielle Georges    646-888-4337    georgesm@mskcc.org   
Principal Investigator: Gregory J. Riely         
Canada, Ontario
Novartis Investigative Site Recruiting
Toronto, Ontario, Canada, M5G 2M9
Germany
Novartis Investigative Site Recruiting
Koeln, Nordrhein-Westfalen, Germany, 50937
Italy
Novartis Investigative Site Recruiting
Milano, MI, Italy, 20133
Japan
Novartis Investigative Site Recruiting
Nagoya, Aichi, Japan, 464-8681
Novartis Investigative Site Recruiting
Fukuoka, Japan, 811-1395
Korea, Republic of
Novartis Investigative Site Recruiting
Seoul, Korea, Korea, Republic of, 03080
Novartis Investigative Site Recruiting
Seoul, Korea, Korea, Republic of, 05505
Netherlands
Novartis Investigative Site Recruiting
Amsterdam, Netherlands, 1066
Singapore
Novartis Investigative Site Recruiting
Singapore, Singapore, 169610
Spain
Novartis Investigative Site Recruiting
Barcelona, Catalunya, Spain, 08035
Novartis Investigative Site Recruiting
Madrid, Spain, 28041
Taiwan
Novartis Investigative Site Recruiting
Taipei, Taiwan ROC, Taiwan, 10041
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02108964     History of Changes
Other Study ID Numbers: CEGF816X2101
2013-004482-14 ( EudraCT Number )
Study First Received: April 7, 2014
Last Updated: June 15, 2017
Individual Participant Data  
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com


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

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
NSCLC
Non-small Cell Lung Cancer EGFRmut
EGFR TKIs (EGF816)
acquired T790M mutation
de novo T790M mutation
EGFR TKI activating mutation (i.e. L858R or ex19del)
Treatment naive advanced NSCLC with EGFR activating mutations
Locally advanced NSCLC (Stage IIIB NSCLC not amenable to definitive multi-modality therapy including surgery)
Metastatic NSCLC refers to Stage IV NSCLC
1st line

Additional relevant MeSH terms:
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

ClinicalTrials.gov processed this record on June 22, 2017