Phase 2 Study of Dacomitinib in NSCLC

NCT04027647 | Active Not Recruiting Phase 2

• 1 other identifier: ATORG-003
• Study Type: interventional
• Target: 118
• Locations: 5 countries
• Sites: 9

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/IIIC/IV or recurrent EGFR-mutation-positive non-small cell lung cancer (NSCLC). National Cancer Centre Singapore is the lead sponsor acting in a coordinating capacity and the rest of the participating sites are sponsors of their own individual sites.

Conditions

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

Keywords

Stage III NSCLC; Stage IV NSCLC; Vizimpro; EGFR TKI; Tyrosine Kinase Inhibitor

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  Percentage of subjects with PFS at 12 months

  From the start of treatment to the date of disease progression or death due to any cause at 12 months

Secondary Outcomes (6)

• Overall Survival

  From the start of treatment to the date of death for any cause, up to 3 years

• Objective Response Rate

  From the start of treatment until disease progression, up to 3 years

• Time to Treatment Failure

  From the start of treatment to the last dose of treatment, up to 3 years

• Intracranial Objective Response Rate

  From the start of treatment until disease progression, up to 3 years

• Intracranial Progression-Free Survival

  From the start of treatment to the date of intracranial progression or death due to any cause, up to 3 years

Study Arms (1)

Treatment

EXPERIMENTAL

Daily administration of oral Dacomitinib

Drug: Dacomitinib

Interventions

Dacomitinib DRUG

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.

Also known as: Vizimpro

Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of a voluntarily given, personally signed and dated, written informed consent document;
• Male or female adult as defined by local regulation;
• 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/IIIC/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:
• At least one target lesion that has not previously been radiated, and is measurable according to RECIST v1.1;
• 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:
• Estimated creatinine clearance ≥30 mL/min (as determined by Cockcroft-Gault formula or the study site's standard formula);
• Absolute neutrophil count (ANC) ≥1500 cells/mm3;
• Platelets ≥100,000 cells/mm3;
• Hemoglobin ≥10.0 g/dL;
• Bilirubin ≤1.5 x ULN;

You may not qualify if:

• 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:
• 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;
• Pre-existing idiopathic pulmonary fibrosis evidenced by CT scan at baseline;
• 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:
• Diagnosed or suspected congenital long QT syndrome;

Sponsors & Collaborators

• National Cancer Centre, Singapore: lead
• Pfizer: collaborator

Study Sites (9)

Prince of Wales Hospital

Hong Kong, Hong Kong

Location

Sarawak General Hospital

Kuching, Sarawak, Malaysia

Location

University Malaya Medical Centre

Kuala Lumpur, Malaysia

Location

Beacon Hospital

Petaling Jaya, Malaysia

Location

National Cancer Centre Singapore

Singapore, Singapore

Location

Dong-A University Hospital

Busan, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

Phramongkutklao Hospital

Bangkok, Thailand

Location

Ramathibodi Hospital

Bangkok, Thailand

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

dacomitinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Daniel Tan, BSc, MBBS, PhD

  National Cancer Centre Singapore (Lead Sponsor)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2019
• First Posted: July 22, 2019
• Study Start: September 11, 2019
• Primary Completion: March 31, 2026
• Study Completion: March 31, 2026
• Last Updated: June 12, 2025

Record last verified: 2025-06

Locations

HK (1); KR (2); TH (2); SG (1); MY (3)