An Open Label, Multicenter, Phase II Study of Dacomitinib for EGFR Mutated Non-Small Cell Lung Cancer (NSCLC) With Brain Metastases

NCT04339829 | Unknown Phase 2

• 1 other identifier: CTONG2001
• Study Type: interventional
• Target: 50
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a multi-center, single-arm, open-label, Phase 2 clinical study of Dacomitinib for EGFR Mutated Non-Small Cell Lung Cancer (NSCLC) With Brain Metastases.

Conditions

Dacomitinib for EGFR Mutated Non-Small Cell Lung Cancer (NSCLC) With Brain Metastases

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival （PFS）

  Progression Free Survival （PFS）is defined as the time from start of treatment to the date of disease progression as defined by RECIST v1.1 per investigator review or death due to any cause, whichever occurred first.

  20 months

Secondary Outcomes (6)

• Intracranial Objective Response Rate

  20 months

• Objective Response Rate

  20 months

• Disease control rate

  20 months

• Duration of response

  20 months

• Intracranial Progression Free Survival

  20 months

Study Arms (1)

Dacomitinib 45mg PO ,QD

OTHER

Single arm

Drug: Dacomitinib

Interventions

Dacomitinib DRUG

Dacomitinib orally on a continuous daily basis at a starting dose of 45 mg QD

Dacomitinib 45mg PO ,QD

Eligibility Criteria

• Age: 18 Years - 80 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;
• Age≥18 years, 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. It is acceptable for subjects with the presence of the exon 20 T790M mutation together with either EGFR activating mutation (exon 19 deletion or the L858R mutation in exon 21) to be included in this study;
• Evidence of newly diagnosed stage IIIB/IV (based on Union for International Cancer Control (UICC) staging system version 7) 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 an EGFR-TKI or other TKIs is not allowed;
• Brain metastases lesions should be more than or equal to 3 metastatic lesions in the brain . At least one target lesion's diameter among these lesions should be more than 1 centimeter（ Patients with CNS metastases. whose condition was neurologically stable were eligible. Any previous definitive treatment or glucocorticoid therapy had to be completed at least 2 weeks before initiation of the trial treatment.）.
• 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);
• Urinary protein \<3+ by urine dipstick. If urine protein by dipstick is ≥3+, then a urine protein/creatinine ratio (UPC) should be obtained. The subject may enter only if UPC is \<2.0;
• Absolute neutrophil count (ANC) ≥1500 cells/mm3;
• Platelets ≥100,000 cells/mm3;

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;
• Any other mutation other than exon 19 deletion or L858R in exon 21, with or without the presence of the exon 20 T790M mutation. Both mutations (exon 19 deletion and L858R mutation in exon 21) within a tumor sample;
• Symptomatic brain or leptomeningeal metastases, who are neurologically unstable or require increasing doses of steroids 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, 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 an 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 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:
• Diagnosed or suspected congenital long QT syndrome;

Sponsors & Collaborators

• Guangdong Association of Clinical Trials: lead

Related Publications (13)

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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 Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice-chairman

Model Details: This is a multi-center, single-arm, open-label, Phase 2 clinical study of Dacomitinib for EGFR Mutated Non-Small Cell Lung Cancer (NSCLC) With Brain Metastases.

Study Record Dates

• First Submitted: April 7, 2020
• First Posted: April 9, 2020
• Study Start: August 1, 2020
• Primary Completion: July 1, 2022
• Study Completion: August 30, 2023
• Last Updated: April 9, 2020

Record last verified: 2020-04