Clinical Trials /

Durvalumab vs Placebo With Stereotactic Body Radiation Therapy in Early Stage Unresected Non-small Cell Lung Cancer Patients

NCT03833154

Description:

This is a Phase III, randomized, placebo-controlled, double-blind, multi-center study assessing the efficacy and safety of durvalumab with SoC SBRT versus placebo with SoC SBRT in patients with unresected clinical Stage I/II lymph node-negative (T1 to T3N0M0) NSCLC.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Durvalumab vs Placebo Following Stereotactic Body Radiation Therapy in Early Stage Non-small Cell Lung Cancer Patients
  • Official Title: A Phase III, Randomized, Placebo-controlled, Double-blind, Multi-center, International Study of Durvalumab Following Stereotactic Body Radiation Therapy (SBRT) for the Treatment of Patients With Unresected Stage I/II, Lymph-node Negative Non-small Cell Lung Cancer (PACIFIC-4/RTOG-3515)

Clinical Trial IDs

  • ORG STUDY ID: D9103C00001
  • SECONDARY ID: 2018-002572-41
  • NCT ID: NCT03833154

Conditions

  • Carcinoma, Non-Small-Cell Lung

Interventions

DrugSynonymsArms
DurvalumabMEDI4736Durvalumab Therapy

Purpose

This is a Phase III, randomized, placebo-controlled, double-blind, multi-center study assessing the efficacy and safety of durvalumab versus placebo following SoC SBRT in patients with unresected clinical Stage I/II lymph node-negative (T1 to T3N0M0) NSCLC.

Detailed Description

      Patients who complete definitive treatment with SoC SBRT and are confirmed to meet all
      eligibility criteria will be randomized 1:1 to durvalumab or placebo.

      The primary objective of this study is to assess the efficacy of durvalumab monotherapy
      compared to placebo in terms of PFS. Key secondary is to assess the efficacy of Durvalumab
      monotherapy compared to placebo in terms of OS.
    

Trial Arms

NameTypeDescriptionInterventions
Durvalumab TherapyExperimentalDurvalumab (PD-L1 monoclonal antibody)1500 mg every 4 weeks [q4w] intravenously [iv] for up to 24 months or until progression or other discontinuation criteria are met.
  • Durvalumab
Placebo TherapyPlacebo ComparatorPlacebo (matching placebo for infusion every 4 weeks iv for up to 24 months or until progression or other discontinuation criteria are met.

    Eligibility Criteria

            Key Inclusion Criteria:
    
              1. Age ≥18 years
    
              2. Histologically or cytologically documented Stage I to II NSCLC, with clinical Stage
                 I/II lymph node-negative (T1 to T3N0M0) disease and planned to receive definitive
                 treatment with SBRT. Patients may be medically inoperable or are medically operable
                 and refusing surgery or choosing to have SBRT (Stereotactic Body Radiation Therapy) as
                 definitive therapy
    
              3. Completion of SoC SBRT as definitive treatment prior to randomization
    
              4. World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) PS of 0, 1,
                 or 2
    
              5. Life expectancy of at least 12 weeks
    
              6. Body weight >30 kg
    
              7. Tumor sample required
    
              8. Adequate organ and marrow function required
    
              9. Patients with central or peripheral lesions are eligible
    
             10. Staging studies must be done within 8 weeks before randomization
    
            Key Exclusion Criteria:
    
              1. Mixed small cell and non-small cell cancer histology
    
              2. History of allogeneic organ transplantation
    
              3. History of another primary malignancy with exceptions
    
              4. History of active primary immunodeficiency
    
              5. Any unresolved toxicity National Cancer Institute (NCI) CTCAE Grade ≥2 from SBRT
                 (Stereotactic Body Radiation Therapy)
          
    Maximum Eligible Age:130 Years
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Progression-Free Survival (PFS) assessed by BICR according to RECIST 1.1 in subpopulation of patients with Stage I/II NSCLC
    Time Frame:up to 5 years
    Safety Issue:
    Description:

    Secondary Outcome Measures

    Measure:Progression-Free Survival (PFS) assessed by BICR per RECIST 1.1 in all randomised patients with Stage I/II NSCLC
    Time Frame:up to 5 years
    Safety Issue:
    Description:
    Measure:Overall Survival (OS)
    Time Frame:up to 6 years
    Safety Issue:
    Description:
    Measure:Lung cancer-specific mortality
    Time Frame:up to 6 years
    Safety Issue:
    Description:
    Measure:Peak Plasma Concentration (Cmax)
    Time Frame:up to 27 months
    Safety Issue:
    Description:
    Measure:Detection of ADA neutralising antibodies titers
    Time Frame:up to 30 months
    Safety Issue:
    Description:
    Measure:Health-related quality of life in patients treated with durvalumab monotherapy compared to placebo using the EORTC QLQ-C30
    Time Frame:up to 6 years
    Safety Issue:
    Description:
    Measure:Proportion of patients alive and progression free at 24 months from randomisation (PFS24) assessed by BICR according to RECIST 1.1
    Time Frame:at 24 months following randomization
    Safety Issue:
    Description:
    Measure:Time to progression (TTP) assessed by BICR according to RECIST 1.1
    Time Frame:up to 5 years
    Safety Issue:
    Description:
    Measure:Time to death or distant metastasis (TTDM) assessed by BICR according to RECIST 1.1
    Time Frame:up to 5 years
    Safety Issue:
    Description:
    Measure:Time from randomisation to second progression (PFS2) as defined by local standard clinical practice
    Time Frame:up to 6 years
    Safety Issue:
    Description:
    Measure:Trough Concentration (Ctrough)
    Time Frame:up to 27 months
    Safety Issue:
    Description:
    Measure:Assessment of AEs by CTCAE v 5.0 as measures of the safety and tolerability of durvalumab compared to placebo after administration of SBRT
    Time Frame:up to 27 months
    Safety Issue:
    Description:

    Details

    Phase:Phase 3
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:AstraZeneca

    Trial Keywords

    • NSCLC
    • Double- Blind
    • PD-L1
    • MEDI4736
    • Durvalumab
    • PFS
    • OS

    Last Updated