Metastatic Non Small Cell Lung Cancer
Conditions
Keywords
Dacomitinib, Metastatic Non Small Cell Lung Cancer, EGFR-activating mutations, NSCLC
Brief summary
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.
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.
Interventions
DRUGDacomitinib
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.
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With All-Causality and Treatment-Related Treatment-Emergent Adverse Events (TEAEs) | From the first dose of study treatment up to 28 days after the last dose of study treatment (maximum treatment duration: 107.3 weeks) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Investigator Assessment | 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 | 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. |
| Duration of Response (DOR) as Per RECIST Version 1.1 Based on Investigator Assessment | 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 | 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. |
Countries
India
Participant flow
Pre-assignment details
A total of 106 participants were screened, 5 participants were screen failures, 101 participants were enrolled and assigned to treatment and all of them were treated.
Participants by arm
| Arm | Count |
|---|---|
| Dacomitinib Participants with metastatic non-small cell lung carcinoma (NSCLC) with epidermal growth factor receptor (EGFR) mutations received a starting dose of dacomitinib 45 mg once daily in each cycle of 28 days, until disease progression, participant refusal/lost to follow-up, or unacceptable toxicity occurred. The maximum treatment duration was approximately 107.3 weeks. | 101 |
| Total | 101 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Follow-Up | Death | 4 |
| Follow-Up | Lost to Follow-up | 2 |
| Follow-Up | Other | 7 |
| Follow-Up | Withdrawal by Subject | 5 |
| Treatment | Death | 5 |
| Treatment | Other | 2 |
| Treatment | Physician Decision | 1 |
| Treatment | Progressive Disease | 61 |
| Treatment | Withdrawal by Subject | 11 |
Baseline characteristics
| Characteristic | Dacomitinib |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 26 Participants |
| Age, Categorical Between 18 and 65 years | 75 Participants |
| Age, Continuous | 55.95 Years STANDARD_DEVIATION 10.89 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 101 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 47 Participants |
| Sex: Female, Male Male | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 9 / 101 |
| other Total, other adverse events | 93 / 101 |
| serious Total, serious adverse events | 16 / 101 |
Outcome results
Primary
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.
Time frame: From the first dose of study treatment up to 28 days after the last dose of study treatment (maximum treatment duration: 107.3 weeks)
Population: All participants who received at least 1 dose of dacomitinib.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dacomitinib | Number of Participants With All-Causality and Treatment-Related Treatment-Emergent Adverse Events (TEAEs) | Number of Participants with all-causality TEAEs | 94 Participants |
| Dacomitinib | Number of Participants With All-Causality and Treatment-Related Treatment-Emergent Adverse Events (TEAEs) | Number of Participants with all-causality SAEs | 16 Participants |
| Dacomitinib | Number of Participants With All-Causality and Treatment-Related Treatment-Emergent Adverse Events (TEAEs) | Number of Participants with treatment-related TEAEs | 92 Participants |
| Dacomitinib | Number of Participants With All-Causality and Treatment-Related Treatment-Emergent Adverse Events (TEAEs) | Number of Participants with treatment-related SAEs | 7 Participants |
Secondary
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.
Time frame: 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
Population: All participants who received at least 1 dose of dacomitinib. DOR was only for the subset participants with an objective response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dacomitinib | Duration of Response (DOR) as Per RECIST Version 1.1 Based on Investigator Assessment | 11.1 Months |
Secondary
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.
Time frame: 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
Population: All participants who received at least 1 dose of dacomitinib.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dacomitinib | Overall Response Rate (ORR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Investigator Assessment | 50.5 Percentage of participants |