Clinical Trials /

Phase 2 Study of Dacomitinib in NSCLC

NCT04027647

Description:

This is a multi-national, multi-centre, single-arm, open-label, Phase 2 clinical study of the efficacy and safety of first-line treatment with dacomitinib, with or without dose titration, in subjects with newly diagnosed stage IIIB/IV or recurrent EGFR-mutation-positive Non-small cell lung cancer (NSCLC).

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase 2 Study of Dacomitinib in NSCLC
  • Official Title: A Single-arm, Open-label, Phase 2 Study of Dacomitinib With or Without Dose Titration for the First-line Treatment of Locally Advanced or Metastatic Non-small Cell Lung Cancer in Subjects With Epidermal Growth Factor Receptor (EGFR) Activation Mutation

Clinical Trial IDs

  • ORG STUDY ID: ATORG003
  • NCT ID: NCT04027647

Conditions

  • NSCLC Stage IIIB
  • NSCLC Stage IV
  • Recurrent NSCLC
  • EGFR Positive Non-Small Cell Lung Cancer

Interventions

DrugSynonymsArms
DacomitinibVizimproTreatment

Purpose

This is a multi-national, multi-centre, single-arm, open-label, Phase 2 clinical study of the efficacy and safety of first-line treatment with dacomitinib, with or without dose titration, in subjects with newly diagnosed stage IIIB/IV or recurrent EGFR-mutation-positive Non-small cell lung cancer (NSCLC).

Trial Arms

NameTypeDescriptionInterventions
TreatmentExperimentalDaily administration of oral Dacomitinib
  • Dacomitinib

Eligibility Criteria

        Inclusion Criteria:

          -  Provision of a voluntarily given, personally signed and dated, written informed
             consent document;

          -  Age ≥20 years in Japan and Korea, and ≥18 years in other countries, male or female;

          -  The presence of an EGFR activating mutation (exon 19 deletion or the L858R mutation in
             exon 21) in tumor specimen determined by the local laboratory;

          -  Evidence of newly diagnosed stage IIIB/IV (based on Union for International Cancer
             Control (UICC) staging system version 8) or recurrent (minimum of 12 months disease
             free interval between completion of systemic therapy and recurrence of NSCLC required)
             NSCLC of adenocarcinoma histo- and/or cytopathology or its pathologically accepted
             variants using tumor specimen (assessed according to accepted standards by a local
             laboratory). For this purpose the World Health Organization/International Association
             of Study of Lung Cancer Histologic Classification of Lung Cancer Criteria will be used
             and the diagnosis of NSCLC NOS (not otherwise specified), squamous or mixed
             adeno-squamous lung carcinomas will not be allowed;

          -  Have an ECOG PS of 0 or 1;

          -  No prior treatment with systemic therapy for locally advanced or metastatic NSCLC.
             Completed neoadjuvant/adjuvant chemotherapy/immunotherapy and/or combined modality
             chemotherapy/radiation therapy permitted only in cases in which there is a minimum of
             12 months disease free interval between completion of systemic therapy and recurrence
             of NSCLC. Prior treatment with a EGFR-TKI or other TKIs is not allowed;

          -  Radiologically measurable disease by RECIST v1.1 criteria:

               1. At least one target lesion that has not previously been radiated, and is
                  measurable according to RECIST v1.1;

               2. Acceptable radiologic procedures for disease assessment include contrast enhanced
                  conventional or spiral computed tomography (CT), or contrast enhanced magnetic
                  resonance imaging (MRI); Non-contrast CT scan is acceptable only for subjects who
                  are both allergic to intravenous contrast and unable to cooperate with MRI, or
                  MRI is not available. The following are not allowed as sole documentation of
                  target lesions: CT component of positron emission tomography (PET)/CT, ultrasound
                  alone, nuclear scans (including bone or PET scans), chest X-ray or bone
                  radiographs, and tumor markers;

          -  Adequate organ function, including:

               1. Estimated creatinine clearance ≥30 mL/min (as determined by Cockcroft-Gault
                  formula or the study site's standard formula);

               2. Absolute neutrophil count (ANC) ≥1500 cells/mm3;

               3. Platelets ≥100,000 cells/mm3;

               4. Hemoglobin ≥10.0 g/dL;

               5. Bilirubin ≤1.5 x ULN;

               6. AST (also known as SGOT) and ALT (also known as SGPT) ≤2.5 x ULN (≤5.0 x ULN if
                  hepatic metastases).

          -  Female subjects must be postmenopausal (defined as 12 months of amenorrhea following
             last menses), or they or their partners must be surgically sterile, or must agree to
             use effective contraception while receiving study treatment and for at least 3 months
             thereafter. The definition of effective contraception will be based on the judgment of
             the investigator using following criteria:

             a. Acceptable contraception for women include implants, injectables, combined oral
             contraceptives, intrauterine devices (IUDs), sexual abstinence, or a partner who has
             been surgically sterile (e.g. by vasectomy) for at least 6 months. Acceptable
             contraception for a male includes surgical sterility (e.g. by vasectomy) for at least
             6 months, sexual abstinence, or condoms plus spermicide.

          -  All female subjects with reproductive potential must have a negative pregnancy test
             (serum or urine) prior to starting study treatment;

          -  Male subjects or their female partners must be surgically sterile or must agree to use
             effective contraception while receiving study treatment and for at least 3 months
             thereafter. The definition of effective contraception will be based on the judgment of
             the investigator. Or female partners must be postmenopausal (defined as 12 months of
             amenorrhea following last menses);

          -  Willing and able to comply with study scheduled visits, treatment plans, laboratory
             tests, and other study procedures.

        Exclusion Criteria:

          -  Any evidence of mixed histo- and/or cytology that includes elements of small cell or
             carcinoid lung cancer. Variations of adenocarcinoma are allowed, however no squamous
             element can be present;

          -  Any other EGFR mutation other than exon 19 deletion or L858R in exon 21. Both
             mutations (exon 19 deletion and L858R mutation in exon 21) co-existing within a tumor
             sample is not allowed;

          -  Symptomatic brain or leptomeningeal metastases, who are neurologically unstable or
             require increasing doses of steroids and/or anti-seizure medications to manage CNS
             symptoms within two weeks prior to starting dacomitinib;

          -  Any previous anti-cancer systemic treatment of locally advanced, or metastatic NSCLC
             including but not limited to chemotherapy, targeted therapies, small molecules,
             EGFR-TKIs and other TKIs, monoclonal antibodies, anti-cancer vaccines, immunotherapy,
             radiotherapy (other than palliative radiotherapy to lesions that will not be followed
             for tumor assessment on this study, i.e., non-target lesions). Completed
             neoadjuvant/adjuvant chemotherapy/immunotherapy and/or combined modality chemotherapy/
             radiation therapy permitted only in cases in which there is a minimum of 12 months
             disease free interval between completion of systemic therapy and recurrence of NSCLC.
             Prior treatment with a EGFR-TKI or other TKIs is not allowed;

          -  Any surgery (not including minor procedures such as lymph node biopsy), palliative
             radiotherapy or pleurodesis within 2 weeks of first dose of study treatment;

          -  Any clinically significant gastrointestinal abnormalities that may impair intake,
             transit or absorption of the study drug, such as the inability to take oral
             medication;

          -  Current enrollment in another therapeutic clinical study;

          -  Any psychiatric or cognitive disorder that would limit the understanding or rendering
             of informed consent and/or compromise compliance with the requirements of this study;
             or known drug abuse/alcohol abuse;

          -  History of, or currently suspected, diffuse non-infectious pneumonitis or interstitial
             lung disease including:

               1. Past medical history of interstitial lung disease, drug-induced interstitial
                  disease, radiation pneumonitis which required steroid treatment or any evidence
                  of clinically active interstitial lung disease;

               2. Pre-existing idiopathic pulmonary fibrosis evidenced by CT scan at screening;

               3. Insufficient lung function as determined by either clinical examination or an
                  arterial oxygen tension of <70 Torr.

          -  Any history of galactose intolerance, Lapp lactase deficiency or glucose-galactose
             malabsorption

          -  Clinically important abnormalities in cardiac rhythm, conduction or morphology of
             resting ECG (e.g. complete left bundle branch block, second degree heart block, third
             degree heart block) OR:

               1. Diagnosed or suspected congenital long QT syndrome;

               2. Any history of clinically significant ventricular arrhythmias (such as
                  ventricular tachycardia, ventricular fibrillation, or Torsades de pointes);

               3. Prolonged QTc interval on ECG; QTc must be less than CTCAE v5.0 Grade 2 (≤480
                  msec) using Fridericia's or Bazett's correction formula with a manual reading by
                  the investigator if required. The ECG may be repeated for evaluation of
                  eligibility after management of correctable causes for observed QTc prolongation;

               4. Any history of second or third degree heart block;

               5. Heart rate <45 beats per minute on ECG in the presence of clinical symptoms
                  (e.g., hypotension, evidence of hypoperfusion);

          -  Severely impaired (defined as Child-Pugh Class C) hepatic dysfunction;

          -  Prior malignancy: Subjects will not be eligible if they have history of, or evidence
             of active disease of another concurrent malignancy within the previous five years.
             Exception would be effectively treated past history of non-melanoma skin cancer or
             in-situ cervical cancer with no evidence of active disease;

          -  Other severe acute or chronic medical condition that may increase the risk associated
             with study participation or investigational drug administration or may interfere with
             the interpretation of study results and, in the judgment of the investigator, would
             make the subject inappropriate for entry into this study;

          -  Use of narrow therapeutic index drugs that are CYP2D6 substrates (procainamide,
             pimozide, and thioridazine etc.) from screening to randomization.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-Free Survival
Time Frame:From the start of treatment to the date of disease progression or death due to any cause, up to 2 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Overall Survival
Time Frame:From the start of treatment to the date of death for any cause, up to 2 years
Safety Issue:
Description:
Measure:Objective Response Rate
Time Frame:From the start of treatment until disease progression, up to 2 years
Safety Issue:
Description:Proportion of subjects with a best overall response of either complete response (CR) or partial response (PR)
Measure:Time to Treatment Failure
Time Frame:From the start of treatment to the last dose of treatment, up to 2 years
Safety Issue:
Description:
Measure:Intracranial Objective Response Rate
Time Frame:From the start of treatment until disease progression, up to 2 years
Safety Issue:
Description:Proportion of subjects with a best overall response of either CR or PR of intracranial disease
Measure:Intracranial Progression-Free Survival
Time Frame:From the start of treatment to the date of intracranial progression or death due to any cause, up to 2 years
Safety Issue:
Description:
Measure:Number of incidences of adverse events
Time Frame:From start of treatment to 28 days after end of treatment
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:National Cancer Centre, Singapore

Trial Keywords

  • Stage 3B NSCLC
  • Stage 4 NSCLC
  • Vizimpro
  • EGFR TKI
  • Tyrosine Kinase Inhibitor

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