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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03833154




Registration number
NCT03833154
Ethics application status
Date submitted
25/01/2019
Date registered
6/02/2019

Titles & IDs
Public title
Durvalumab with Stereotactic Body Radiation Therapy (SBRT) Vs Placebo with SBRT in Early Stage Unresected Non-small Cell Lung Cancer (NSCLC) Patients/ Osimertinib Following SBRT in Patients with Early Stage Unresected NSCLC Harboring an EGFR Mutation
Scientific title
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) Osimertinib Following SBRT, a Single Arm Cohort for Patients with Unresected Stage I/II, Lymph Node Negative NSCLC Harboring a Sensitizing EGFR Mutation
Secondary ID [1] 0 0
2018-002572-41
Secondary ID [2] 0 0
D9103C00001
Universal Trial Number (UTN)
Trial acronym
PACIFIC-4
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Carcinoma, Non-Small-Cell Lung 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Durvalumab
Other interventions - Placebo
Treatment: Drugs - (Osimertinib cohort, single-arm, open-label separate cohort)

Experimental: SoC SBRT + Durvalumab Therapy (Main Cohort) - SBRT

Durvalumab (PD-L1 monoclonal antibody) 1500 mg every 4 weeks \[q4w\] intravenously \[iv\] for up to 26 cycles or until progression or other discontinuation criteria are met.

Placebo comparator: SoC SBRT + Placebo Therapy (Main Cohort) - SBRT

Placebo (matching placebo for infusion) every 4 weeks iv for up to 26 cycles or until progression or other discontinuation criteria are met.

Experimental: SoC SBRT + Osimertinib Therapy (Osimertinib cohort, single-arm, open-label separate cohort) - SBRT

Osimertinib 80mg every day \[qd\] for oral administration up to 36 months or until progression. Osimertinib treatment should start within 7 to 14 days after completion of SBRT


Treatment: Drugs: Durvalumab
Durvalumab 1500 mg every 4 weeks \[q4w\] intravenously \[iv\] for up to 26 cycles or until progression or other discontinuation criteria are met.

Other interventions: Placebo
Matching placebo for infusion every 4 weeks iv for up to 26 cycles or until progression or other discontinuation criteria are met.

Treatment: Drugs: (Osimertinib cohort, single-arm, open-label separate cohort)
Osimertinib 80 mg every day \[qd\] orally for up to 36 months or until progression or other discontinuation criteria are met. Osimertinib treatment should start from 7 to 14 days after completion of SBRT
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-Free Survival (PFS) assessed by Blinded Independent Central Review (BICR) according to RECIST 1.1 in subpopulation of patients with Stage I/II NSCLC
Timepoint [1] 0 0
from randomization up to 6 years
Primary outcome [2] 0 0
4-year Progression-Free Survival (4y-PFS) by ICR according to RECIST 1.1 criteria
Timepoint [2] 0 0
from treatment start up to 5 years
Secondary outcome [1] 0 0
Progression-Free Survival (PFS) assessed by BICR per RECIST 1.1 in all randomised patients with Stage I/II NSCLC
Timepoint [1] 0 0
from randomization up to 6 years
Secondary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
from randomization up to 7 years
Secondary outcome [3] 0 0
Concentration of durvalumab in serum such as peak concentration and trough
Timepoint [3] 0 0
12 weeks after last dose
Secondary outcome [4] 0 0
Detection of ADA neutralising antibodies titers
Timepoint [4] 0 0
up to 6 months after last dose
Secondary outcome [5] 0 0
Health-related quality of life in patients treated with durvalumab with SoC SBRT compared to placebo with SoC SBRT using the EORTC QLQ-C30
Timepoint [5] 0 0
from randomization up to 7 years
Secondary outcome [6] 0 0
Proportion of patients alive and progression free at 24 months from randomisation (PFS24) assessed by BICR according to RECIST 1.1
Timepoint [6] 0 0
at 24 months following randomization
Secondary outcome [7] 0 0
Time to progression (TTP) assessed by BICR according to RECIST 1.1
Timepoint [7] 0 0
from randomization up to 6 years
Secondary outcome [8] 0 0
Time to death or distant metastasis (TTDM) assessed by BICR according to RECIST 1.1
Timepoint [8] 0 0
from randomization up to 6 years
Secondary outcome [9] 0 0
Time from randomisation to second progression (PFS2) as defined by local standard clinical practice
Timepoint [9] 0 0
from randomization up to 7 years
Secondary outcome [10] 0 0
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
Timepoint [10] 0 0
up to 3 months after last dose
Secondary outcome [11] 0 0
Assessment of AEs by CTCAE v 5.0 as measures of the safety, tolerability and compliance of osimertinib with SoC SBRT therapy
Timepoint [11] 0 0
Up to 35 days after last dose
Secondary outcome [12] 0 0
WHO performance status
Timepoint [12] 0 0
from treatment start up to 5 years
Secondary outcome [13] 0 0
ECG QT interval
Timepoint [13] 0 0
Up to 156 weeks of treatment or treatment discontinuation
Secondary outcome [14] 0 0
Overall Survival
Timepoint [14] 0 0
from treatment start up to 5 years
Secondary outcome [15] 0 0
Time To Progression (TTP)
Timepoint [15] 0 0
from treatment start up to 5 years
Secondary outcome [16] 0 0
Time to CNS progression
Timepoint [16] 0 0
from treatment start up to 5 years
Secondary outcome [17] 0 0
PFS2
Timepoint [17] 0 0
from treatment start up to 5 years
Secondary outcome [18] 0 0
Site(s) of disease progression
Timepoint [18] 0 0
from treatment start up to 5 years
Secondary outcome [19] 0 0
PFS by ICR using RECIST 1.1
Timepoint [19] 0 0
from treatment start up to 5 years

Eligibility
Key inclusion criteria
Main Cohort Key

1. Age =18 years
2. Planned SoC SBRT as definitive treatment
3. World Health Organization (WHO)/ECOG PS of 0, 1 or 2
4. Life expectancy of at least 12 weeks
5. Body weight >30 kg
6. Submission of tumor tissue sample if available
7. Adequate organ and marrow function required
8. Patients with central or peripheral lesions are eligible
9. Staging studies must be done during screening (PET-CT within 10 weeks)
10. Patients with a history of metachronous NSCLC and synchronous lesions are eligible with some exceptions

Main Cohort Key
Minimum age
18 Years
Maximum age
130 Years
Sex
Both males and females
Can healthy volunteers participate?
No
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
5. Epidermal growth factor receptor local testing is strongly recommended prior to enrollment. Patients with a tumor harboring an EGFRm per local testing will be excluded from the main cohort
6. Prior exposure to immune-mediated therapy with exceptions

Osimertinib Cohort Key Inclusion Criteria

1. Age =18 years
2. Planned SoC SBRT as definitive treatment
3. WHO/ECOG PS of 0, 1, or 2
4. Patients with central or peripheral lesions are eligible
5. Patients with a history of metachronous NSCLC and synchronous lesions are eligible with some exceptions
6. Staging studies must be done during screening (PET-CT within 10 weeks)
7. Submission of tumor tissue sample if available
8. Confirmation by local laboratory that the tumor harbors one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R)
9. Adequate bone marrow reserve or organ function required
10. Female patients should be using highly effective contraceptive measures
11. Male patients should be asked to use barrier contraceptives (ie, condoms) during sex with all partners during the trial and avoid procreation

Osimertinib Cohort Key Exclusion Criteria

1. Mixed small cell and non-small cell cancer
2. Patients with known or increased risk factor for QTc prolongation
3. Treatment with any of the following:

* Preoperative or adjuvant platinum-based or other chemotherapy for the disease under investigation
* Prior treatment with neoadjuvant or adjuvant EGFR TKI
* Patients currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be potent inducers of CYP3A4
4. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of osimertinib
5. Any of the following cardiac criteria

* Mean resting corrected QT interval >470 msec, obtained from 3 ECGs
* Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG.
* Any factors that increase the risk of QTc prolongation or risk of arrhythmic events, or unexplained -sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval
* Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
6/03/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
4/04/2028
Actual
Sample size
Target
Accrual to date
Final
724
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Clayton
Recruitment postcode(s) [1] 0 0
3168 - Clayton
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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United States of America
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Arizona
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United States of America
State/province [3] 0 0
California
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United States of America
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Delaware
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United States of America
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District of Columbia
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Florida
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Georgia
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Illinois
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Indiana
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Iowa
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Kentucky
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Louisiana
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Maine
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Maryland
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Massachusetts
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Missouri
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Nebraska
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Nevada
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New Hampshire
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New Jersey
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New York
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North Carolina
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North Dakota
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Ohio
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Oregon
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Pennsylvania
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South Carolina
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South Dakota
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Texas
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Vermont
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Virginia
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Washington
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Wisconsin
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Belgium
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Aalst
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Belgium
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Charleroi
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Belgium
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Edegem
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Belgium
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Gent
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Belgium
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Leuven
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Brazil
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Barretos
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Porto Alegre
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Recife
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Rio de Janeiro
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Sao Paulo
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Brazil
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Volta Redonda
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Canada
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Alberta
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Ontario
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Beijing
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Wenzhou
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Wuhan
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Lyon Cedex 04
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Nantes
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Halle
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Heidelberg
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Germany
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Homburg
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Germany
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Trier
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Greece
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Athens
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Greece
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Thessaloniki
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Haifa
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Jerusalem
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Kfar Saba
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Petah Tikva
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Israel
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Ramat Gan
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Israel
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Tel Aviv
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Italy
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Firenze
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Italy
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Genova
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Italy
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Milano
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Italy
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Orbassano
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Italy
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Padova
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Italy
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Pavia
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Italy
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Roma
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Italy
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Rozzano
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Japan
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Akashi-shi
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Sunto-gun
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Toyoake-shi
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Yokohama-shi
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Korea, Republic of
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Goyang-si
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Gyeonggi-do
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Korea, Republic of
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Seoul
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Netherlands
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Amsterdam
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Groningen
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Utrecht
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Elblag
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Lódz
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Puerto Rico
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Hato Rey
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Russian Federation
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Ekaterinburg
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Russian Federation
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Kazan, Tatarstan
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Russian Federation
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Moscow
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Russian Federation
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Saint Petersburg
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Ufa
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Badajoz
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Barcelona
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Spain
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L'Hospitalet de Llobregat
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Madrid
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Malaga
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Spain
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San Sebastián
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Santiago de Compostela
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Sevilla
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Spain
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Valencia
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Spain
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Zaragoza
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Turkey
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Ankara
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Turkey
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Istanbul
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Turkey
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Izmir
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Turkey
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Kocaeli
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United Kingdom
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Birmingham
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United Kingdom
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Leeds
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United Kingdom
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London
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United Kingdom
State/province [146] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
AstraZeneca Clinical Study Information Center
Address 0 0
Country 0 0
Phone 0 0
1-877-240-9479
Fax 0 0
Email 0 0
information.center@astrazeneca.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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 document/s available: Study protocol, Statistical analysis plan (SAP)
When will data be available (start and end dates)?
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.
Available to whom?
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.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://astrazenecagroup-dt.pharmacm.com/DT/Home


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT03833154