Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Durvalumab vs Placebo With Stereotactic Body Radiation Therapy in Early Stage Unresected Non-small Cell Lung Cancer Patients (PACIFIC-4)

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: NCT03833154
Recruitment Status : Recruiting
First Posted : February 6, 2019
Last Update Posted : April 19, 2021
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE January 25, 2019
First Posted Date  ICMJE February 6, 2019
Last Update Posted Date April 19, 2021
Actual Study Start Date  ICMJE March 6, 2019
Estimated Primary Completion Date June 28, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 4, 2020)
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 6 years ]
Original Primary Outcome Measures  ICMJE
 (submitted: February 5, 2019)
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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 4, 2020)
  • Progression-Free Survival (PFS) assessed by BICR per RECIST 1.1 in all randomised patients with Stage I/II NSCLC [ Time Frame: up to 6 years ]
  • Overall Survival (OS) [ Time Frame: up to 7 years ]
  • Lung cancer-specific mortality [ Time Frame: up to 7 years ]
  • Peak Plasma Concentration (Cmax) [ Time Frame: up to 27 months ]
  • Detection of ADA neutralising antibodies titers [ Time Frame: up to 30 months ]
  • Health-related quality of life in patients treated with durvalumab with SoC SBRT compared to placebo with SoC SBRT using the EORTC QLQ-C30 [ Time Frame: up to 7 years ]
  • 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 ]
  • Time to progression (TTP) assessed by BICR according to RECIST 1.1 [ Time Frame: up to 6 years ]
  • Time to death or distant metastasis (TTDM) assessed by BICR according to RECIST 1.1 [ Time Frame: up to 6 years ]
  • Time from randomisation to second progression (PFS2) as defined by local standard clinical practice [ Time Frame: up to 7 years ]
  • Trough Concentration (Ctrough) [ Time Frame: up to 27 months ]
  • Assessment of AEs by CTCAE v 5.0 as measures of the safety and tolerability of durvalumab with SoC SBRT compared to placebo with SoC SBRT [ Time Frame: up to 27 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: February 5, 2019)
  • 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 ]
  • Overall Survival (OS) [ Time Frame: up to 6 years ]
  • Lung cancer-specific mortality [ Time Frame: up to 6 years ]
  • Peak Plasma Concentration (Cmax) [ Time Frame: up to 27 months ]
  • Detection of ADA neutralising antibodies titers [ Time Frame: up to 30 months ]
  • 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 ]
  • 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 ]
  • Time to progression (TTP) assessed by BICR according to RECIST 1.1 [ Time Frame: up to 5 years ]
  • Time to death or distant metastasis (TTDM) assessed by BICR according to RECIST 1.1 [ Time Frame: up to 5 years ]
  • Time from randomisation to second progression (PFS2) as defined by local standard clinical practice [ Time Frame: up to 6 years ]
  • Trough Concentration (Ctrough) [ Time Frame: up to 27 months ]
  • 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Durvalumab vs Placebo With Stereotactic Body Radiation Therapy in Early Stage Unresected Non-small Cell Lung Cancer Patients
Official Title  ICMJE A Phase III, Randomized, Placebo-controlled, Double-blind, Multi-center, International Study of Durvalumab With 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)
Brief Summary 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.
Detailed Description

Patients who are to receive SoC SBRT as definitive treatment of stage I-II lymph node-negative NSCLC and 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 with SoC SBRT compared to placebo with SoC SBRT in terms of PFS. Key secondary is to assess the efficacy of Durvalumab with SoC SBRT compared to placebo with SoC SBRT in terms of OS.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Double- Blind
Primary Purpose: Treatment
Condition  ICMJE Carcinoma, Non-Small-Cell Lung
Intervention  ICMJE
  • Drug: Durvalumab
    Durvalumab 1500 mg every 4 weeks [q4w] intravenously [iv] for up to 24 months or until progression or other discontinuation criteria are met.
    Other Name: MEDI4736
  • Other: Placebo
    Matching placebo for infusion every 4 weeks iv for up to 24 months or until progression or other discontinuation criteria are met.
  • Radiation: SBRT
    Delivered in 3, 4, 5 or 8 fractions.
Study Arms  ICMJE
  • Experimental: SoC SBRT + Durvalumab Therapy

    SBRT - delivered in 3, 4, 5 or 8 fractions.

    Durvalumab (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.

    Interventions:
    • Drug: Durvalumab
    • Radiation: SBRT
  • Placebo Comparator: SoC SBRT + Placebo Therapy

    SBRT - delivered in 3, 4, 5 or 8 fractions.

    Placebo (matching placebo for infusion every 4 weeks iv for up to 24 months or until progression or other discontinuation criteria are met.

    Interventions:
    • Other: Placebo
    • Radiation: SBRT
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 24, 2020)
706
Original Estimated Enrollment  ICMJE
 (submitted: February 5, 2019)
630
Estimated Study Completion Date  ICMJE October 31, 2025
Estimated Primary Completion Date June 28, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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. Planned SoC SBRT as definitive treatment
  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. Submission of available tumor tissue sample
  8. Adequate organ and marrow function required
  9. Patients with central or peripheral lesions are eligible
  10. Staging studies must be done within 10 weeks before randomization
  11. Patients with a history of metachronus stage I/II (T1-T3N0M0) NSCLC treated definitively surgery only or SBRT only >1 year prior to enrollment are eligible.

Key Exclusion Criteria:

  1. Mixed small cell and non-small cell cancer
  2. History of allogeneic organ transplantation
  3. History of another primary malignancy with exceptions
  4. History of active primary immunodeficiency
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 130 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
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
Listed Location Countries  ICMJE Belgium,   Canada,   China,   France,   Germany,   Israel,   Italy,   Japan,   Korea, Republic of,   Netherlands,   Poland,   Puerto Rico,   Russian Federation,   Spain,   Turkey,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03833154
Other Study ID Numbers  ICMJE D9103C00001
2018-002572-41 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account AstraZeneca
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP