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Study of Dacomitinib and Osimertinib for Patients With Advanced EGFR Mutant Lung Cancer

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ClinicalTrials.gov Identifier: NCT03810807
Recruitment Status : Recruiting
First Posted : January 21, 2019
Last Update Posted : May 23, 2019
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Brief Summary:
The purpose of this study is to test the safety of dacomitinib and osimertinib, at increasing doses, to find out what effects, if any, this combination of drugs has on people with metastatic EGFR mutant lung cancer that has not been treated with an EGFR TKI.

Condition or disease Intervention/treatment Phase
Metastatic Non-small Cell Lung Cancer Drug: Dacomitinib Drug: Osimertinib Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 34 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1 Study of Combination Dacomitinib and Osimertinib for Patients With Metastatic EGFR Mutant Lung Cancers
Actual Study Start Date : January 17, 2019
Estimated Primary Completion Date : January 2021
Estimated Study Completion Date : January 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
Drug Information available for: Osimertinib

Arm Intervention/treatment
Experimental: Dacomitinib and Osimertinib

Patients will begin on combination dacomitinib and osimertinib at the prescribed doses.

A cycle will be 28 days in duration. The study will use a standard 3+3 dose escalation design.

Drug: Dacomitinib
Dose level 1 Dacomitinib, Dose level 2 Dacomitinib, Dose level 3 Dacomitinib, Dose level 4 Dacomitinib. Three patients will need to be enrolled at each dose level and assessed for DLT for 1 full cycle (28 days for cycle 1) before dose escalation decision is made.

Drug: Osimertinib
Dose level 1, 2 and 3 Osimertinib 40mg daily, Dose level 4 80mg BID. Three patients will need to be enrolled at each dose level and assessed for DLT for 1 full cycle (28 days for cycle 1) before dose escalation decision is made.




Primary Outcome Measures :
  1. maximum tolerated dose [ Time Frame: 1 year ]
    The MTD will be defined as the highest dose at which not more than 1/6 of the patients experience dose limiting toxicity (DLT). DLT is defined as any of the toxicity events described below that occurs within cycle 1 of treatment with the combination of dacomitinib and osimertinib.

  2. Best overall response rate [ Time Frame: 1 year ]
    Tumor response will be assessed using RECIST 1.1.The NCI Common Terminology Criteria for Adverse Events Version 5 (NCI-CTCAE) will be used to grade toxicities during the trial. Dose-limiting toxicities (DLT‟s) are defined as any of the following events occurring during the first cycle of treatment



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Ages Eligible for Study:   19 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent
  • Advanced biopsy-proven metastatic non-small cell lung cancer
  • Somatic activating mutation in EGFR in a tumor biopsy
  • No prior EGFR inhibitor treatment (gefitinib, afatinib, erlotinib, dacomitinib, osimertinib) however, prior treatment with other chemotherapies are allowed
  • Archival tissue available from a pre-treatment tumor biopsy or willing to undergo a tumor biopsy prior to study initiation.
  • Measurable (RECIST 1.1) indicator lesion not previously irradiated
  • Karnofsky performance status (KPS) ≥ 70%
  • Age >18 years old
  • Ability to swallow oral medication
  • Agree to use effective methods of contraception from the time of screening until 3 months after treatment discontinuation (for males and females of child-bearing potential)
  • Adequate organ function

    • AST, ALT ≤ 3 x ULN
    • Total bilirubin ≤1.5x ULN
    • Creatinine ≤ 1.5x ULN OR calculated creatinine clearance ≥ 60ml/min
    • Absolute neutrophil count (ANC) ≥ 1000 cells/mm^3
    • Hemoglobin≥9.0 g/dL
    • Platelets ≥100,000/mm^3

Exclusion Criteria:

  • Pregnant or lactating women
  • Any radiotherapy within 1 week of starting treatment on protocol.
  • Any major surgery within 1 weeks of starting treatment on protocol.
  • Any evidence of active clinically significant interstitial lung disease
  • A mean QTc >470ms (Fridericia‟s correction), clinically important arrhythmia, conduction or morphology of resting ECG (eg complete LBBB, 1st -3rd degree heart block, any factors that increase the risk of QTc prolongation or risk of arrhythmia)
  • Cardiovascular disease or cerebrovascular disease, CVA or MI < 6 months prior to study enrollment, unstable angina, NYHA >Grade II CHF, or serious cardiac arrhythmia uncontrolled by medication or with the potential to interfere with protocol treatment
  • History of pneumonitis or interstitial lung disease (ILD), drug induced ILD, radiation pneumonitits that required steroid treatment, and any evidence of clinically active ILD
  • Serious chronic GI conditions associated with diarrhea
  • Symptomatic, unstable brain metastases requiring escalating doses of steroids
  • Continue to have unresolved > CTCAE grade 1 toxicity from any previous treatment

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): NCT03810807


Contacts
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Contact: Helena Yu, MD 646-888-4274 yuh@mskcc.org
Contact: Gregory Riely, MD, PhD 646-888-4199

Locations
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United States, New Jersey
Memoral Sloan Kettering Basking Ridge Recruiting
Basking Ridge, New Jersey, United States, 07920
Contact: Helena Yu, MD    646-888-4274      
Memorial Sloan Kettering Monmouth Recruiting
Middletown, New Jersey, United States, 07748
Contact: Helena Yu, MD    646-888-4274      
Memorial Sloan Kettering Bergen Recruiting
Montvale, New Jersey, United States, 07645
Contact: Helena Yu, MD    646-888-4274      
United States, New York
Memorial Sloan Kettering Commack Recruiting
Commack, New York, United States, 11725
Contact: Helena Yu, MD    646-888-4274      
Memoral Sloan Kettering Westchester Recruiting
Harrison, New York, United States, 10604
Contact: Helena Yu, MD    646-888-4274      
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Helena Yu, MD    646-888-4274      
Contact: Gregory Riely, MD, PhD    646-888-4199      
Principal Investigator: Helena Yu, MD         
Memorial Sloan Kettering Nassau Recruiting
Uniondale, New York, United States, 11553
Contact: Helena Yu, MD    646-888-4274      
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Investigators
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Principal Investigator: Helena Yu, MD Memorial Sloan Kettering Cancer Center

Additional Information:
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Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT03810807     History of Changes
Other Study ID Numbers: 18-411
First Posted: January 21, 2019    Key Record Dates
Last Update Posted: May 23, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.
Supporting Materials: Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Memorial Sloan Kettering Cancer Center:
Dacomitinib
Osimertinib
EGFR Mutant Lung Cancers
18-411
Additional relevant MeSH terms:
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Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Osimertinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action