Dacomitinib for Treatment of Patients in India With Metastatic Non Small Cell Lung Cancer With EGFR Activating Mutations

SINGLE ARM STUDY TO EVALUATE THE SAFETY OF DACOMITINIB FOR THE FIRST-LINE TREATMENT OF PARTICIPANTS IN INDIA WITH METASTATIC NON-SMALL CELL LUNG CANCER WITH EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR)-ACTIVATING MUTATIONS

This is a Phase 4, open label, single arm, multi-center, prospective clinical trial of dacomitinib that will be performed in India. This study will enroll a sufficient number of participants to ensure that 100 participants are treated with dacomitinib. The primary objective of this study is to assess the safety and tolerability of dacomitinib. The secondary objective is to evaluate antitumor activity of dacomitinib by objective response rate and duration of response.

Study Overview

• Status: Completed
• Conditions: Metastatic Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: Dacomitinib

Detailed Description

This is a Phase 4, open label, single arm, multi-center, prospective clinical trial of dacomitinib that will be performed in India. This study will enroll a sufficient number of participants to ensure that 100 participants are treated with dacomitinib. The primary objective of this study is to assess the safety and tolerability of dacomitinib. The secondary objective is to evaluate antitumor activity of dacomitinib by objective response rate and duration of response. Drug administration: Dacomitinib will be supplied by Pfizer and administered in accordance with the India Local Product Document (LPD). The recommended dosage of dacomitinib is 45 mg taken orally once a day at approximately the same time each day, until disease progression, participant refusal/lost to follow-up, or unacceptable toxicity occurs.

STUDY PROCEDURES:

Screening: Participants will be screened within 28 days prior to first dosing of dacomitinib to confirm that they meet the eligibility criteria for the study.

Follow-up Visit: All participants will return to the study site up to 28 days after the last dose of study drug administration for assessment of potential AEs, recording of concomitant treatment use and to confirm appropriate contraception usage.

ASSESSMENTS Tumor Assessments: Tumor assessments will include all known or suspected disease sites. Computerized tomography (CT) or Magnetic resonance imaging (MRI) scans of Chest Abdomen and Pelvis and MRI of the brain will be performed at Screening and repeated every 12 weeks ±1 week until the end of treatment. For all tumor assessments, the method of assessment that was used at Screening will be used throughout the study. Tumor assessment will be repeated at the end of treatment if more than 6 weeks have passed since the last evaluation. Assessment of response will be made using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Confirmation of response will be required ≥4 weeks after initial response is observed.

Safety Assessments: The following parameters will be assessed - Physical examination, vital signs, Eastern Cooperative Oncology Group Performance score (ECOG PS), safety lab data, 12 lead electrocardiogram (ECG). Unscheduled clinical laboratory measurements may be obtained at any time during the study to assess any perceived safety concerns.

Adverse event reporting: All observed or volunteered AEs regardless of treatment group or suspected causal relationship to the investigational product(s) will be reported as per regulatory requirements.

End of Study: The end of study is defined as 1 year after the last participant first visit (LPFV) date in the study. At the end of study, participants who are on treatment and benefiting from dacomitinib treatment will be switched to commercially available dacomitinib if considered appropriate by the investigator, as soon as feasible.

• Study Type: Interventional
• Enrollment (Actual): 101
• Phase: Phase 4

Contacts and Locations

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110085
      • Rajiv Gandhi Cancer Institute and Research Centre
  • Gujarat
    • Ahmedabad, Gujarat, India, 380016
      • The Gujarat Cancer and Research Institute
    • Ahmedabad, Gujarat, India, 380054
      • Hemato Oncology Clinic Ahmedabad Pvt. Ltd
    • Surat, Gujarat, India, 395009
      • Unity Trauma Center And ICU (Unity Hospital )
    • Surat, Gujarat, India, 395009
      • Gujarat Hospital - Gastro & Vascular Centre
  • Haryana
    • Gurugram, Haryana, India, 122001
      • Artemis hospital
  • Maharashtra
    • Nagpur, Maharashtra, India, 441108
      • National Cancer Institute
    • Nashik, Maharashtra, India, 422009
      • Apex Wellness Hospital
    • Pune, Maharashtra, India, 411004
      • Sahyadri Super Speciality Hospital
    • Pune, Maharashtra, India, 411001
      • Grant Medical Foundation, Ruby Hall Clinic
    • Pune, Maharashtra, India, 411004
      • Sahyadri Clinical Research and Development Center
    • Thane, Maharashtra, India, 401107
      • Bhaktivedanta Hospital and Research Institute
  • Telangana State
    • Hyderabad, Telangana State, India, 500082
      • Yashoda Hospital
  • WEST Bengal
    • Kolkata, WEST Bengal, India, 700160
      • Tata Medical Center
    • Kolkata, WEST Bengal, India, 700094
      • Netaji Subhas Chandra Bose Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Evidence of histologically or cytologically confirmed diagnosis of metastatic NSCLC with EGFR activating mutations as detected by an appropriate test.
2. No prior treatment with systemic therapy and EGFR/Other Tyrosine Kinase Inhibitors (TKIs) for metastatic NSCLC.
3. Participants with asymptomatic Central Nervous System (CNS) metastases (including participants controlled with stable or decreasing steroid use within the last 2 weeks prior to study entry) will be eligible.
4. Age >=18 years.
5. ECOG PS of 0-2.
6. Adequate . hematologic, renal, liver function: ANC >= 1000/mm3; Platelets>=50000/mm3; Hb >=8 g/dL; est. Cr.Cl >=30 mL/min; Total serum bilirubin <1.5 × ULN; AST,ALT <=2.5 × ULN; (<=5.0 × ULN, if liver metastases).
7. Acute effects of any prior therapy resolved to baseline severity or to Common Terminology Criteria for Adverse Events (CTCAE) Grade <1 except for AEs that in the investigator's judgment do not constitute a safety risk for the participant.
8. Serum or urine pregnancy test (for females of childbearing potential) negative at Screening.

Exclusion Criteria:

1. Any evidence of mixed histology that includes elements of small cell or carcinoid lung cancer.
2. Any other mutation other than exon 19 deletion or L858R in exon 21, with or without the presence of the exon 20 T790M mutation.
3. Radiation therapy (except palliative to relieve bone pain) within 2 weeks of study entry. Prior irradiation to >25% of the bone marrow.
4. Major surgery within 4 weeks prior to first dose of dacomitinib. Minor surgical procedures (eg, port insertion) are not excluded, but sufficient time should have passed for adequate wound healing.
5. Known prior or suspected severe hypersensitivity to dacomitinib or any component of its formulation.
6. History or known presence of interstitial fibrosis, interstitial lung disease, pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, obliterative bronchiolitis, and pulmonary fibrosis.
7. Other severe acute or chronic medical or psychiatric condition, that may interfere with the interpretation of study results and, would make the participant inappropriate for entry into this study.
8. Evidence of active malignancy (other than current NSCLC) within the last 3 years prior to first dose of dacomitinib.
9. Breastfeeding female participants.
10. Pregnant female participants; male participants able to father children and female participants of childbearing potential who are unwilling or unable to use contraception method per protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Arm; The recommended dosage of dacomitinib is 45 mg taken orally once a day at approximately the same time each day, until disease progression, participant refusal/lost to follow-up, or unacceptable toxicity occurs.	Drug: Dacomitinib; Dacomitinib is a kinase inhibitor indicated for the first line treatment of patients with metastatic NSCLC with EGFR exon 19 deletion or exon 21 L858R substitution mutations.; Other Names: DACOPLICE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With All-Causality and Treatment-Related Treatment-Emergent Adverse Events (TEAEs)	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Relatedness to study drug was assessed by the investigator. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to approximately 107.3 weeks that were absent before treatment or that worsened relative to pretreatment state.	From the first dose of study treatment up to 28 days after the last dose of study treatment (maximum treatment duration: 107.3 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Investigator Assessment	Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST. Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. Per RECIST v1.1: CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). No new lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. Stable disease was defined as not qualifying for CR, PR, Progressive Disease.	From time of first dose until disease progression, death or initiation of a new anticancer therapy, whichever occurs first, assessed for up to 26 months
Duration of Response (DOR) as Per RECIST Version 1.1 Based on Investigator Assessment	DOR: time from first documented occurrence of response (PR or CR) until date of first documented PD or death due to underlying cancer. RECIST 1.1. CR: disappearance of all non-nodal target lesions and of all non-target lesions. In addition, any pathological lymph nodes assigned as target lesions/ non-target lesions must have a reduction in short axis to <10 mm. PR: at least a 30% decrease in sum of diameter of all target lesions, taking as reference baseline sum of diameters. PD: at least a 20% increase in sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, sum must also demonstrate an absolute increase of at least 5 mm^2. Unequivocal progression of existing non-target lesions. Appearance of new lesions. Participants with no PD and were still alive, were censored at last adequate tumor assessment. Kaplan-Meier method was used for DOR analysis.	From time of first tumor response until disease progression, death or initiation of a new anticancer therapy, whichever occurs first, assessed for up to 26 months

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): August 27, 2020
• Primary Completion (Actual): October 15, 2022
• Study Completion (Actual): November 8, 2022

Study Registration Dates

• First Submitted: July 30, 2020
• First Submitted That Met QC Criteria: August 11, 2020
• First Posted (Actual): August 13, 2020

Study Record Updates

• Last Update Posted (Actual): April 5, 2024
• Last Update Submitted That Met QC Criteria: April 3, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: NSCLC; Dacomitinib; Metastatic Non Small Cell Lung Cancer; EGFR-activating mutations
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Tyrosine Kinase Inhibitors; Dacomitinib
• Other Study ID Numbers: A7471064

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No