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A Study of Durvalumab as Consolidation Therapy in Non-Small Cell Lung Cancer Patients (PACIFIC-5)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03706690
Recruitment Status : Recruiting
First Posted : October 16, 2018
Last Update Posted : January 6, 2020
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
This is a Phase III, randomised, double-blind, placebo-controlled, multicentre study assessing the efficacy and safety of durvalumab compared with placebo, as consolidation therapy in patients with locally advanced, unresectable, non-small cell lung cancer (Stage III), who have not progressed following definitive, platinum-based, chemoradiation therapy.

Condition or disease Intervention/treatment Phase
Carcinoma, Non-Small-Cell Lung Drug: Durvalumab Other: Placebo Phase 3

Detailed Description:
Approximately 360 patients will be randomized in a 2:1 to receive treatment with durvalumab or placebo therapy. EGFR or ALK mutation randomised will be capped at approximately 15%. The primary objective of this study is to assess the efficacy of durvalumab treatment compared with placebo in terms of PFS(according to Blinded Independent Central Review).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 360 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Sponsor, excluding supply chain management personnel and unblinded monitors of site pharmacies, will remain blinded.
Primary Purpose: Treatment
Official Title: A Phase III, Randomised,Double-Blind,Placebo-Controlled,Study of Durvalumab as Consolidation Therapy in Patients With Locally Advanced,Unresectable NSCLC, Who Have Not Progressed Following Definitive, Platinum-Based Chemoradiation Therapy
Actual Study Start Date : November 27, 2018
Estimated Primary Completion Date : March 25, 2021
Estimated Study Completion Date : January 31, 2025

Resource links provided by the National Library of Medicine

Drug Information available for: Durvalumab

Arm Intervention/treatment
Experimental: Durvalumab Therapy
Durvalumab (PD-L1 monoclonal antibody)1500 mg every 4 weeks [q4w] intravenously [iv] until clinical progression/deterioration or confirmed radiological progression)
Drug: Durvalumab
Durvalumab 1500 mg every 4 weeks [q4w] intravenously [iv] until clinical progression/ deterioration or confirmed radiological progression.
Other Name: MEDI4736

Placebo Comparator: Placebo Therapy
Placebo (matching placebo for infusion every 4 weeks iv until clinical progression/deterioration or confirmed radiological progression)
Other: Placebo
Matching placebo for infusion every 4 weeks iv until clinical progression/deterioration or confirmed radiological progression




Primary Outcome Measures :
  1. Progression-Free Survival (PFS) assessed by BICR according to RECIST 1.1 in randomised patients [ Time Frame: from date of randomisation until disease progression, assessed up to 29months ]
    To assess the efficacy of durvalumab treatment compared with placebo in terms of PFS


Secondary Outcome Measures :
  1. The efficacy of durvalumab treatment compared to placebo in terms of Overall Survival (OS) in randomised patients [ Time Frame: from date of randomisation until the date of death, assessed up to 65 months ]
    To further assess the efficacy of durvalumab compared with placebo in terms of OS

  2. The efficacy of durvalumab treatment compared to placebo in terms of proportion of patients alive at 24 months (OS24) from randomisation. [ Time Frame: at 24 months from participants' randomisation. ]
    To further assess the efficacy of durvalumab compared with placebo in terms of OS24

  3. Objective Response Rate (ORR) assessed by BICR according to RECIST 1.1 in randomised patients [ Time Frame: from date of randomisation until progression, or the last evaluable assessment in the absence of progression, assessed up to 29months ]
    To further assess the efficacy of durvalumab compared with placebo in terms of ORR.

  4. Duration of Response (DoR) assessed by BICR according to RECIST 1.1 in randomised patients [ Time Frame: from date of randomisation until progression, or the last evaluable assessment in the absence of progression, assessed up to 29months ]
    To further assess the efficacy of durvalumab compared with placebo in terms of DOR

  5. Proportion of patients alive and progression free from randomisation to second progression (PFS2) as defined by local standard clinical practice [ Time Frame: from randomisation to second progression. assessed up to 65months ]
    The date of PFS2 assessment and Investigator opinion of progression status (progressed or non-progressed) at each assessment will be recorded in the PFS2 eCRF.

  6. Proportion of patients alive and progression free at 12 months from randomisation (PFS12) assessed by BICR according to RECIST 1.1 in randomised patients [ Time Frame: at 12 months from participants' randomisation. ]
    To further assess the efficacy of durvalumab compared with placebo in terms of PFS12

  7. Proportion of patients alive and progression free at 18 months from randomisation (PFS18) assessed by BICR according to RECIST 1.1. [ Time Frame: at 18 months from participants' randomisation. ]
    To further assess the efficacy of durvalumab compared with placebo in terms of PFS18

  8. Proportion of patients at time to death or distant metastasis (TTDM) assessed by BICR according to RECIST 1.1 in randomised patients [ Time Frame: date of randomisation until the first date of distant metastasis or death in the absence of distant metastasis, assessed up to 65months ]
    To further assess the efficacy of durvalumab compared with placebo in terms of TTDM.

  9. Peak Plasma Concentration (Cmax) in randomised patients [ Time Frame: at scheduled visits from randomisation to 3months after treatment discontinuation. ]
    To assess the PK of durvalumab

  10. Trough Concentration (Ctrough) in randomised patients [ Time Frame: at scheduled visits from randomisation to 3months after treatment discontinuation. ]
    To assess the PK of durvalumab

  11. Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [ Time Frame: from randomisation until 3 months after treatment discontinuation. ]
    All AE data will be listed and the treatment-emergence status will be flagged in the listing.

  12. Detection of ADA neutralising antibodies titres for all randomised patients [ Time Frame: at scheduled visits from randomisation to 6months after treatment discontinuation. ]
    To investigate the immunogenicity of durvalumab

  13. IHC analysis of tumoural PD-L1 expression and spatial distribution within the tumour microenvironment relative to efficacy outcome OS [ Time Frame: from date of randomisation until the date of death from any cause, whichever came first, assessed up to 65months ]
    To investigate the relationship between a patient's baseline tumour PD-L1 expression and OS with durvalumab compared with placebo

  14. IHC analysis of tumoural PD-L1 expression and spatial distribution within the tumour microenvironment relative to efficacy outcome PFS [ Time Frame: from date of randomisation until disease progression, assessed up to 29months ]
    To investigate the relationship between a patient's baseline tumour PD-L1 expression and PFS with durvalumab compared with placebo

  15. IHC analysis of tumoural PD-L1 expression and spatial distribution within the tumour microenvironment relative to efficacy outcome ORR [ Time Frame: from date of randomisation until progression, or the last evaluable assessment in the absence of progression, assessed up to 29months ]
    To investigate the relationship between a patient's baseline tumour PD-L1 expression and ORR with durvalumab compared with placebo

  16. Number of participants with abnormal findings with physical examination [ Time Frame: At scheduled visits from screening to 30days after treatment discontinuation ]
    To assess physical examination as variable of safety and tolerability of durvalumab in participants

  17. vital sign (blood pressure [BP]) [ Time Frame: change from baseline up to follow up/early termination visits (30days after treatment discontinuation) ]
    To assess blood pressure as variable of safety and tolerability of durvalumab in participants.

  18. vital sign (pulse rate) [ Time Frame: change from baseline up to follow up/early termination visits (30days after treatment discontinuation) ]
    To assess pulse rate as variable of safety and tolerability of durvalumab in participants.

  19. vital sign (temperature) [ Time Frame: change from baseline up to follow up/early termination visits (30days after treatment discontinuation) ]
    To assess temperature as variable of safety and tolerability of durvalumab in participants.

  20. vital sign (respiration rate) [ Time Frame: change from baseline up to follow up/early termination visits (30days after treatment discontinuation) ]
    To assess respiration rate as variable of safety and tolerability of durvalumab in participants.

  21. vital sign (12-lead electrocardiogram) [ Time Frame: change from baseline up to follow up/early termination visits (30days after treatment discontinuation) ]
    To assess 12-lead electrocardiogram as variable of safety and tolerability of durvalumab in participants.

  22. Change in Albumin (g/L) [ Time Frame: at scheduled visits from randomisation to 3months after treatment discontinuation. ]
    Data for Albumin recorded in the eCRF will be listed and summarized by treatment group and visit.

  23. Change in Alkaline phosphatase (U/L) [ Time Frame: at scheduled visits from randomisation to 3months after treatment discontinuation. ]
    Data for Alkaline phosphatase recorded in the eCRF will be listed and summarized by treatment group and visit.

  24. Change in Alanine aminotransferase (U/L) [ Time Frame: at scheduled visits from randomisation to 3months after treatment discontinuation. ]
    Data for Alanine aminotransferase recorded in the eCRF will be listed and summarized by treatment group and visit.

  25. Change in Aspartate aminotransferase (U/L) [ Time Frame: at scheduled visits from randomisation to 3months after treatment discontinuation. ]
    Data for Aspartate aminotrasnferase recorded in the eCRF will be listed and summarized by treatment group and visit.

  26. Change in Amylase (U/L) [ Time Frame: at scheduled visits from randomisation to 3months after treatment discontinuation. ]
    Data for Amylase recorded in the eCRF will be listed and summarized by treatment group and visit.

  27. Change in Bicarbonate (mmol/L) [ Time Frame: at scheduled visits from randomisation to 3months after treatment discontinuation. ]
    Data for Bicarbonate recorded in the eCRF will be listed and summarized by treatment group and visit.

  28. Change in Calcium (mmol/L) [ Time Frame: at scheduled visits from randomisation to 3months after treatment discontinuation. ]
    Data for Calcium recorded in the eCRF will be listed and summarized by treatment group and visit.

  29. Change in Chloride (mmol/L) [ Time Frame: at scheduled visits from randomisation to 3months after treatment discontinuation. ]
    Data for Chloride recorded in the eCRF will be listed and summarized by treatment group and visit.

  30. Change in Creatinine (μmol/L) [ Time Frame: at scheduled visits from randomisation to 3months after treatment discontinuation. ]
    Data for Creatinine recorded in the eCRF will be listed and summarized by treatment group and visit.

  31. Change in Gamma glutamyltransferase (U/L) [ Time Frame: at scheduled visits from randomisation to 3months after treatment discontinuation. ]
    Data for Gamma glutamyltransferase recorded in the eCRF will be listed and summarized by treatment group and visit.

  32. Change in Glucose (mmol/L) [ Time Frame: at scheduled visits from randomisation to 3months after treatment discontinuation. ]
    Data for Glucose recorded in the eCRF will be listed and summarized by treatment group and visit.

  33. Change in Lactate dehydrogenase (U/L) [ Time Frame: at scheduled visits from randomisation to 3months after treatment discontinuation. ]
    Data for Lactate dehydrogenase recorded in the eCRF will be listed and summarized by treatment group and visit.

  34. Change in Lipase (U/L) [ Time Frame: at scheduled visits from randomisation to 3months after treatment discontinuation. ]
    Data for Lipase recorded in the eCRF will be listed and summarized by treatment group and visit.

  35. Change in Magnesium (mmol/L) [ Time Frame: at scheduled visits from randomisation to 3months after treatment discontinuation. ]
    Data for Magnesium recorded in the eCRF will be listed and summarized by treatment group and visit.

  36. Change in Potassium (mmol/L) [ Time Frame: at scheduled visits from randomisation to 3months after treatment discontinuation. ]
    Data for Potassium recorded in the eCRF will be listed and summarized by treatment group and visit.

  37. Change in Sodium (mmol/L) [ Time Frame: at scheduled visits from randomisation to 3months after treatment discontinuation. ]
    Data for Sodium recorded in the eCRF will be listed and summarized by treatment group and visit.

  38. Change in Total bilirubin (μmol/L) [ Time Frame: at scheduled visits from randomisation to 3months after treatment discontinuation. ]
    Data for total bilirubin recorded in the eCRF will be listed and summarized by treatment group and visit.

  39. Change in total protein (g/L) [ Time Frame: at scheduled visits from randomisation to 3months after treatment discontinuation. ]
    Data for protein recorded in the eCRF will be listed and summarized by treatment group and visit.

  40. Change in TSH (mIU/L) [ Time Frame: at scheduled visits from randomisation to 3months after treatment discontinuation. ]
    Data for TSH recorded in the eCRF will be listed and summarized by treatment group and visit.

  41. Change in T3 free (reflex) (mIU/L) [ Time Frame: at scheduled visits from randomisation to 3months after treatment discontinuation. ]
    Data for free T3 recorded in the eCRF will be listed and summarized by treatment group and visit.

  42. Change in T4 free (reflex) (mIU/L) [ Time Frame: at scheduled visits from randomisation to 3months after treatment discontinuation. ]
    Data for free T4 recorded in the eCRF will be listed and summarized by treatment group and visit.

  43. Change in Urea or blood urea nitrogen, depending on the local practice (mmol/L) [ Time Frame: at scheduled visits from randomisation to 3months after treatment discontinuation. ]
    Data for urea nitrogen recorded in the eCRF will be listed and summarized by treatment group and visit.

  44. Change in Uric acid (mmol/L) [ Time Frame: at scheduled visits from randomisation to 3months after treatment discontinuation. ]
    Data for uric acid recorded in the eCRF will be listed and summarized by treatment group and visit.

  45. Change in absolute neutrophil count (/L) [ Time Frame: at scheduled visits from randomisation to 3months after treatment discontinuation. ]
    Data for absolute neutrophil recorded in the eCRF will be listed and summarized by treatment group and visit.

  46. Change in absolute lymphocyte count (/L) [ Time Frame: at scheduled visits from randomisation to 3months after treatment discontinuation. ]
    Data for absolute lymphocyte recorded in the eCRF will be listed and summarized by treatment group and visit.

  47. Change in haemoglobin (g/L) [ Time Frame: at scheduled visits from randomisation to 3months after treatment discontinuation. ]
    Data for haemoglobin recorded in the eCRF will be listed and summarized by treatment group and visit.

  48. Change in platelet count (/L) [ Time Frame: at scheduled visits from randomisation to 3months after treatment discontinuation. ]
    Data for platelet count recorded in the eCRF will be listed and summarized by treatment group and visit.

  49. Change in total white blood cell count (/L) [ Time Frame: at scheduled visits from randomisation to 3months after treatment discontinuation. ]
    Data for WBC count recorded in the eCRF will be listed and summarized by treatment group and visit.

  50. Change in activated partial thromboplastin time [ Time Frame: at screening and as clinical needed before treatment disocontinuation, assessed up to 65months ]
    Data for active partial thromboplastin recorded in the eCRF will be listed and summarized by treatment group and visit.

  51. Change in international normalised ratio [ Time Frame: at screening and as clinical needed before treatment disocontinuation, assessed up to 65months ]
    Data for international normalised ratio recorded in the eCRF will be listed and summarized by treatment group and visit.

  52. Urinalysis: Change in bilirubin (μmol/L) [ Time Frame: at screening and as clinical needed before treatment disocontinuation, assessed up to 65months ]
    Data for bilirubin recorded in the eCRF will be listed and summarized by treatment group and visit.

  53. Urinalysis: Change in blood [ Time Frame: at screening and as clinical needed before treatment disocontinuation, assessed up to 65months ]
    Data for blood testing recorded in the eCRF will be listed and summarized by treatment group and visit.

  54. Urinalysis: Change in color and apprearance [ Time Frame: at screening and as clinical needed before treatment disocontinuation, assessed up to 65months ]
    color and apprearance of urine recorded in the eCRF will be listed and summarized by treatment group and visit.

  55. Urinalysis: Change in ketones (mmol/L) [ Time Frame: at screening and as clinical needed before treatment disocontinuation, assessed up to 65months ]
    Data for ketones in urine recorded in the eCRF will be listed and summarized by treatment group and visit.

  56. Urinalysis: Change in pH [ Time Frame: at screening and as clinical needed before treatment disocontinuation, assessed up to 65months ]
    Data for urine pH recorded in the eCRF will be listed and summarized by treatment group and visit.

  57. Urinalysis: Change in protein (g/L) [ Time Frame: at screening and as clinical needed before treatment disocontinuation, assessed up to 65months ]
    Data for protein recorded in the eCRF will be listed and summarized by treatment group and visit.

  58. Urinalysis: Change in specific gravity [ Time Frame: at screening and as clinical needed before treatment disocontinuation, assessed up to 65months ]
    Data for gravity recorded in the eCRF will be listed and summarized by treatment group and visit.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age≥18 years
  2. Documented NSCLC and present with locally advanced, unresectable (Stage III) disease;
  3. Receipt of concurrent or sequential chemoradiation therapy,
  4. No progression following definitive, platinum-based, concurrent or sequential chemoradiation therapy
  5. World Health Organization (WHO) PS of 0 or 1;
  6. No prior exposure to any anti CTLA-4, anti-PD-1, anti-PD-L1, or anti PD L2 antibodies, excluding therapeutic anticancer vaccines
  7. Adequate organ and marrow function required
  8. Life expectancy of at least 12 weeks
  9. Tumor PD-L1 status, with the Ventana SP263 PD-L1 IHC assay determined by a reference laboratory, must be known prior to randomization.
  10. Tumour sample requirements are as follows: Provision of a tumour tissue sample (newly acquired sample <=3 months old is preferred, but an archived sample <=6 months old is acceptable) in a quantity sufficient to allow for analysis.

Exclusion Criteria:

  1. History of allogeneic organ transplantation, or another primary malignancy, or active primary immunodeficiency.
  2. Active or prior documented autoimmune or inflammatory disorders
  3. Uncontrolled intercurrent illness that would limit compliance with study requirement, substantially increase risk of incurring AEs, or compromise the ability of the patient to give written informed consent
  4. Active infection including tuberculosis hepatitis B hepatitis C (HCV), or human immunodeficiency virus (positive human immunodeficiency virus [HIV] 1/2 antibodies).
  5. Mixed small cell and NSCLC histology
  6. Any unresolved toxicity National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥2 from the prior chemoradiation therapy.
  7. Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.
  8. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03706690


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Contact: Astrazeneca Cancer Study Locator Service 1-877-400-4656 AstraZeneca@emergingmed.com

Locations
Show Show 90 study locations
Sponsors and Collaborators
AstraZeneca
Investigators
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Principal Investigator: Yilong Wu, MD Guangdong General Hospital, Guangdong Lung Cancer Institute

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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03706690    
Other Study ID Numbers: D933YC00001
First Posted: October 16, 2018    Key Record Dates
Last Update Posted: January 6, 2020
Last Verified: January 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by AstraZeneca:
NSCLC
Double-Blind
PD-L1
MEDI4736
Durvalumab
PFS
OS
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Durvalumab
Antibodies, Monoclonal
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs