Phase 2 Study of Dacomitinib in NSCLC

NCT04027647

Last updated date
Study Location
Chinese University of Hong Kong
Hong Kong, , , Hong Kong
Contact
+65 6436 8000

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
NSCLC Stage IIIB, NSCLC Stage IV, Recurrent NSCLC, EGFR Positive Non-Small Cell Lung Cancer
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- 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
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- 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;


- An EGFR exon 20 T790M or exon 20 insertion mutation;


- 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 baseline assessments;


- 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 baseline;


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


- Any history of rare hereditary problems of galactose intolerance, total 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 study 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 CYP2D6 substrates where minimal increases in concentration of the CYP2D6
substrate may lead to serious or life-threatening toxicities, including but not
limited to procainamide, pimozide, and thioridazine from screening to randomization.

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NSCLC Stage IIIB, NSCLC Stage IV, Recurrent NSCLC, EGFR Positive Non-Small Cell Lung CancerPhase 2 Study of Dacomitinib in NSCLC
NCT04027647
  1. Hong Kong,
  2. Hong Kong,
  3. Busan,
  4. Seoul,
  5. Kuching, Sarawak
  6. Kuala Lumpur,
  7. Taipei,
  8. Bangkok,
  9. Bangkok,
  10. Singapore,
ALL GENDERS
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE Phase 2 Study of Dacomitinib in NSCLC
Official Title  ICMJE 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 an Epidermal Growth Factor Receptor (EGFR) Activation Mutation
Brief Summary

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).

National Cancer Centre Singapore will be the lead sponsor acting in a coordinating capacity and the rest of the participating sites are sponsors of their own individual sites.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • NSCLC Stage IIIB
  • NSCLC Stage IV
  • Recurrent NSCLC
  • EGFR Positive Non-Small Cell Lung Cancer
Intervention  ICMJE Drug: Dacomitinib
30mg of oral dacomitinib is administered daily for one cycle. After one cycle, a toxicity assessment will be conducted. Subjects will then continue dacomitinib at either 30mg or 45mg.
Other Name: Vizimpro
Study Arms  ICMJE Experimental: Treatment
Daily administration of oral Dacomitinib
Intervention: Drug: Dacomitinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 18, 2019)
118
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 28, 2024
Estimated Primary Completion Date June 30, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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;
  • An EGFR exon 20 T790M or exon 20 insertion mutation;
  • 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 baseline assessments;
  • 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 baseline;
    3. Insufficient lung function as determined by either clinical examination or an arterial oxygen tension of <70 Torr.
  • Any history of rare hereditary problems of galactose intolerance, total 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 study 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 CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities, including but not limited to procainamide, pimozide, and thioridazine from screening to randomization.
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Daniel Tan, BSc, MBBS, PhD+65 6436 8000[email protected]
Listed Location Countries  ICMJE Hong Kong,   Korea, Republic of,   Malaysia,   Singapore,   Thailand
Removed Location Countries Taiwan
 
Administrative Information
NCT Number  ICMJE NCT04027647
Other Study ID Numbers  ICMJE ATORG-003
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD:Yes
Responsible Party National Cancer Centre, Singapore
Study Sponsor  ICMJE National Cancer Centre, Singapore
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Principal Investigator:Daniel Tan, BSc, MBBS, PhDNational Cancer Centre Singapore (Lead Sponsor)
PRS Account National Cancer Centre, Singapore
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP