Clinical Trials List
Protocol NumberD4191C00001
2014-08-01 - 2021-11-19
Phase III
Terminated6
ICD-10C34.90
Malignant neoplasm of unspecified part of unspecified bronchus or lung
ICD-10C34.91
Malignant neoplasm of unspecified part of right bronchus or lung
ICD-10C34.92
Malignant neoplasm of unspecified part of left bronchus or lung
ICD-10C7A.090
Malignant carcinoid tumor of the bronchus and lung
ICD-10Z51.12
Encounter for antineoplastic immunotherapy
ICD-9162.9
Malignant neoplasm of bronchus and lung, unspecified
A Phase III, Randomised, Double-blind, Placebo-controlled, Multi-centre, International Study of MEDI4736 as Sequential Therapy in Patients with Locally Advanced, Unresectable Non-Small Cell Lung Cancer (Stage III) Who Have Not Progressed Following Definitive, Platinum-based, Concurrent Chemoradiation Therapy (PACIFIC)
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Trial Applicant
IQVIA RDS Taiwan Ltd.
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Sponsor
AstraZeneca AB
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Jen-Fu Shih Division of Thoracic Medicine
- 吳杰鴻 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Po-Hao Feng Division of Thoracic Medicine
- Chih-Cheng Chang Division of Thoracic Medicine
- Tzu-Tao Chen Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- TSUNG -YING YANG Division of Thoracic Medicine
- 陳焜結 Division of Thoracic Medicine
- JENG-SEN TSENG Division of Thoracic Medicine
- KUO-HSUAN HSU Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- LAI-LEI TING Division of Radiation Therapy
- Chi-Li Chung Division of Thoracic Medicine
- CHIA-CHUN KUO Division of Radiation Therapy
- 林賜恩 Division of Others
- Shih-Hsin Hsiao Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Jih-Hsiang Lee Division of Hematology & Oncology
- 陳冠宇 Division of General Internal Medicine
- 林育麟 Division of Hematology & Oncology
- 廖唯昱 Division of General Internal Medicine
- Chia-Chi Lin Division of Hematology & Oncology
- JIN-YUAN SHIH Division of General Internal Medicine
- 蔡子修 Division of General Internal Medicine
- Chong-Jen Yu Division of General Internal Medicine
- CHAO-CHI HO CHAO-CHI HO Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Wei-Chun Chen Division of Thoracic Medicine
- Chih-Yen Tu Division of Thoracic Medicine
- Chen Chia-Hung Division of Thoracic Medicine
- 陳鴻仁 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
Non-Small Cell Lung Cancer
Objectives
Primary Objective:
- To assess the efficacy of MEDI4736 treatment compared with placebo in terms of OS and PFS.
Secondary Objective:
- To further assess the efficacy of MEDI4736 compared with placebo in terms of: OS24, ORR, DoR, APF12, APF18, PFS2 and DSR.
- To assess the safety and tolerability profile of MEDI4736 compared with placebo.
- To assess the PK of MEDI4736.
- To investigate the immunogenicity of MEDI4736.
- To assess symptoms and health-related quality of life in patients treated with MEDI4736 compared with placebo using EORTC QLQ-C30 v3 and LC13.
Exploratory Objective:
- To explore irRC criteria as an assessment methodology for clinical benefit of MEDI4736 compared with placebo by BICR.
- To investigate the relationship between MEDI4736 PK exposure and clinical outcomes, efficacy, AEs and/or safety parameters, if deemed appropriate.
- To describe and evaluate resource use associated with MEDI4736 treatment and underlying disease.
- To explore the impact of treatment and disease state on health state utility using the EQ-5D-5L.
- To investigate the relationship between a patient’s PD-L1 expression and spatial distribution within the tumour microenvironment and efficacy outcomes with MEDI4736.
- To collect blood and tissue samples for analysis of peripheral and tumoural biomarkers.
- To explore the relationship(s) between a patient’s biomarker status and MEDI4736 PK exposure and clinical outcomes before and after treatment.
- To explore potential biomarkers in residual biological samples (eg, tumour, plasma and/or serum), which may influence the progression of cancer (and associated clinical characteristics) and/or prospectively identify patients likely to respond to MEDI4736 treatment.
- To collect and store DNA according to each country’s local and ethical procedures for future exploratory research into genes/genetic variation that may influence response (ie, distribution, safety, tolerability and efficacy) to study drugs and/or susceptibility to disease (optional)
Test Drug
MEDI4736
Active Ingredient
MEDI4736
Dosage Form
lyophilised powder for infusion
Dosage
200 mg/vial
Endpoints
1.ORR using investigator site assessments according to RECIST 1.1
2.To further assess the efficacy of MEDI4736 compared with placebo in terms of: OS24, ORR, DoR, APF12, APF18, PFS2 and DSR according to RECIST 1.1
3.AEs, physical examinations, vital signs including blood pressure, pulse, electrocardiograms, and laboratory findings including clinical chemistry, haematology and
urinalysis.
4.Concentration of MEDI4736 in blood and non-compartmental PK parameters.
5.ADA
6.Tumoural expression of PD-L1 and spatial distribution within the tumour microenvironment relative to efficacy outcomes.
2.To further assess the efficacy of MEDI4736 compared with placebo in terms of: OS24, ORR, DoR, APF12, APF18, PFS2 and DSR according to RECIST 1.1
3.AEs, physical examinations, vital signs including blood pressure, pulse, electrocardiograms, and laboratory findings including clinical chemistry, haematology and
urinalysis.
4.Concentration of MEDI4736 in blood and non-compartmental PK parameters.
5.ADA
6.Tumoural expression of PD-L1 and spatial distribution within the tumour microenvironment relative to efficacy outcomes.
Inclution Criteria
Inclusion criteria:
1.Provision of signed, written and dated informed consent prior to any study specific procedures.
2.Male or female aged 18 years or older.
3.Patients must have histologically- or cytologically-documented NSCLC who present with locally advanced, unresectable (Stage III) disease. (according to Version 7 of the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology [IASLC Staging Manual in Thoracic Oncology]), OR
4.Patients must have received at least 2 cycles of platinum-based chemotherapy concurrent with radiation therapy, which must be completed within 5 to 10 days prior to randomisation in the study.
5.Patients must have not progressed following definitive, platinum-based, concurrent
chemoradiation therapy.
6.Tumour sample requirements:
- Mandatory provision of an unstained, archived tumour tissue sample in a quantity
sufficient to allow for analysis.
- A recent tumour biopsy (taken following completion of the most recent therapy) is an optional requirement, provided that a biopsy procedure is technically feasible and the procedure is not associated with unacceptable clinical risk.
7.Life expectancy ≥12 weeks
8.World Health Organization (WHO) Performance Status of 0 or 1.
9.Evidence of post-menopausal status, or negative urinary or serum pregnancy test for
female pre-menopausal patients.
10.Adequate organ and marrow function.
1.Provision of signed, written and dated informed consent prior to any study specific procedures.
2.Male or female aged 18 years or older.
3.Patients must have histologically- or cytologically-documented NSCLC who present with locally advanced, unresectable (Stage III) disease. (according to Version 7 of the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology [IASLC Staging Manual in Thoracic Oncology]), OR
4.Patients must have received at least 2 cycles of platinum-based chemotherapy concurrent with radiation therapy, which must be completed within 5 to 10 days prior to randomisation in the study.
5.Patients must have not progressed following definitive, platinum-based, concurrent
chemoradiation therapy.
6.Tumour sample requirements:
- Mandatory provision of an unstained, archived tumour tissue sample in a quantity
sufficient to allow for analysis.
- A recent tumour biopsy (taken following completion of the most recent therapy) is an optional requirement, provided that a biopsy procedure is technically feasible and the procedure is not associated with unacceptable clinical risk.
7.Life expectancy ≥12 weeks
8.World Health Organization (WHO) Performance Status of 0 or 1.
9.Evidence of post-menopausal status, or negative urinary or serum pregnancy test for
female pre-menopausal patients.
10.Adequate organ and marrow function.
Exclusion Criteria
Exclusion criteria:
Patients should not enter the study if any of the following exclusion criteria are fulfilled:
1.Involvement in the planning and/or conduct of the study.
2.Previous enrolment or randomisation in the present study.
3. Participation in another clinical study with an investigational product during the last 4 weeks.
4.Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study.
5.Mixed small cell and non-small cell lung cancer histology.
6.Patients who receive sequential chemoradiation therapy for locally advanced NSCLC.
7. Patients with locally advanced NSCLC who have progressed whilst definitive platinum based, concurrent chemoradiation therapy.
8.Receipt of any immunotherapy, or investigational drug within 4 weeks prior to the
first dose of study drug; and in the case of monoclonal antibodies 6 weeks prior to
the first dose of study drug.
9.Current or prior use of immunosuppressive medication within 28 days before the
first dose of study drug.
10.Prior exposure to any anti-PD-1 or anti-PD-L1 antibody.
11.Any unresolved toxicity CTCAE >Grade 2 from the prior chemoradiation therapy. Patients with irreversible toxicity that is not reasonably expected to be exacerbated by study drug may be included (eg, hearing loss) after consultation with the AstraZeneca/MedImmune medical monitor.
12.Patients with any grade pneumonitis from prior chemoradiation therapy.
13.Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1.
14.Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for
cancer treatment.
15.Recent major surgery within 4 weeks prior to entry into the study (excluding the placement of vascular access) that would prevent administration of study drug.
16.Active or prior documented autoimmune disease within the past 2 years.
17.Active or prior documented inflammatory bowel disease.
18.History of primary immunodeficiency.
19.History of organ transplant that requires therapeutic immunosuppression.
20.History of hypersensitivity to MEDI4736 or any excipient.
21. History of leptomeningeal carcinomatosis.
22. Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Bazett’s Correction.
23. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any patient known to have hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the patient to give written informed consent.
24. Known history of tuberculosis.
25. Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving study drug.
26. History of another primary malignancy within 5 years prior to starting study drug, except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ and the disease under study.
27. Female patients who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control.
28. Any condition that, in the opinion of the investigator, would interfere with evaluation of the study drug or interpretation of patient safety or study results.
Patients should not enter the study if any of the following exclusion criteria are fulfilled:
1.Involvement in the planning and/or conduct of the study.
2.Previous enrolment or randomisation in the present study.
3. Participation in another clinical study with an investigational product during the last 4 weeks.
4.Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study.
5.Mixed small cell and non-small cell lung cancer histology.
6.Patients who receive sequential chemoradiation therapy for locally advanced NSCLC.
7. Patients with locally advanced NSCLC who have progressed whilst definitive platinum based, concurrent chemoradiation therapy.
8.Receipt of any immunotherapy, or investigational drug within 4 weeks prior to the
first dose of study drug; and in the case of monoclonal antibodies 6 weeks prior to
the first dose of study drug.
9.Current or prior use of immunosuppressive medication within 28 days before the
first dose of study drug.
10.Prior exposure to any anti-PD-1 or anti-PD-L1 antibody.
11.Any unresolved toxicity CTCAE >Grade 2 from the prior chemoradiation therapy. Patients with irreversible toxicity that is not reasonably expected to be exacerbated by study drug may be included (eg, hearing loss) after consultation with the AstraZeneca/MedImmune medical monitor.
12.Patients with any grade pneumonitis from prior chemoradiation therapy.
13.Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1.
14.Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for
cancer treatment.
15.Recent major surgery within 4 weeks prior to entry into the study (excluding the placement of vascular access) that would prevent administration of study drug.
16.Active or prior documented autoimmune disease within the past 2 years.
17.Active or prior documented inflammatory bowel disease.
18.History of primary immunodeficiency.
19.History of organ transplant that requires therapeutic immunosuppression.
20.History of hypersensitivity to MEDI4736 or any excipient.
21. History of leptomeningeal carcinomatosis.
22. Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Bazett’s Correction.
23. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any patient known to have hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the patient to give written informed consent.
24. Known history of tuberculosis.
25. Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving study drug.
26. History of another primary malignancy within 5 years prior to starting study drug, except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ and the disease under study.
27. Female patients who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control.
28. Any condition that, in the opinion of the investigator, would interfere with evaluation of the study drug or interpretation of patient safety or study results.
The Estimated Number of Participants
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Taiwan
25 participants
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Global
1000 participants
