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JOURNAL ONKOLOGIE – STUDIE
PACIFIC-4

Durvalumab vs Placebo With Stereotactic Body Radiation Therapy 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

Rekrutierend

NCT-Nummer:
NCT03833154

Studienbeginn:
März 2019

Letztes Update:
11.04.2024

Wirkstoff:
Durvalumab, Osimertinib (single-arm, open-label)

Indikation (Clinical Trials):
Lung Neoplasms, Carcinoma, Non-Small-Cell Lung

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 3

Sponsor:
AstraZeneca

Collaborator:
-

Kontakt

AstraZeneca Clinical Study Information Center
Kontakt:
Phone: 1-877-240-9479
E-Mail: information.center@astrazeneca.com» Kontaktdaten anzeigen
Astrazeneca Cancer Study Locator Service
Kontakt:
Phone: 1-877-400-4656
E-Mail: AstraZeneca@emergingmed.com» Kontaktdaten anzeigen

Studienlocations
(3 von 277)

Research Site
47228 Duisburg
(Nordrhein-Westfalen)
GermanyZurückgezogen» Google-Maps
Research Site
40489 Düsseldorf
(Nordrhein-Westfalen)
GermanyZurückgezogen» Google-Maps
Research Site
37075 Göttingen
(Niedersachsen)
GermanyRekrutierend» Google-Maps
Research Site
30459 Hannover
(Niedersachsen)
GermanyRekrutierend» Google-Maps
Research Site
69126 Heidelberg
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Research Site
58675 Hemer
(Nordrhein-Westfalen)
GermanyZurückgezogen» Google-Maps
Research Site
55131 Mainz
(Rheinland-Pfalz)
GermanyZurückgezogen» Google-Maps
Research Site
54292 Trier
(Rheinland-Pfalz)
GermanyRekrutierend» Google-Maps
Research Site
10709 Newark
United StatesAktiv, nicht rekrutierend» Google-Maps
Research Site
08043 Voorhees
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
10016 New York
United StatesAktiv, nicht rekrutierend» Google-Maps
Research Site
05819 Saint Johnsbury
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
28644 Cheongju-si
Korea, Republic ofRekrutierend» Google-Maps
Research Site
13620 Gyeonggi-do
Korea, Republic ofRekrutierend» Google-Maps
Research Site
420029 Kazan, Tatarstan
Russian FederationSchwebend» Google-Maps
Research Site
197758 Saint Petersburg
Russian FederationSchwebend» Google-Maps
Research Site
197758 Saint-Petersburg
Russian FederationZurückgezogen» Google-Maps
Research Site
197758 St. Petersburg
Russian FederationZurückgezogen» Google-Maps
Research Site
08907 L'Hospitalet de Llobregat
SpainRekrutierend» Google-Maps
Research Site
TS4 3BW Middlesborough
United KingdomRekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

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 main cohort 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 Overall Survival (OS).

In addition, a study cohort with a sufficient number of patients harboring an EGFR mutation,

will receive Osimertinib treatment after completion of SoC SBRT as definitive treatment of

Stage I/II lymph node-negative NSCLC. The primary objective of Osimertinib cohort is to

assess efficacy of Osimertinib following SoC SBRT in terms of 4years-PFS. Key secondary

objectives include safety, OS and efficacy of Osimertininb treatment with SBRT.

Ein-/Ausschlusskriterien

Main 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. 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 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. World Health Organization (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 available tumor tissue sample

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 currently receiving potent inducers of CYP3A4

3. Patients with known or increased risk factor for QTc prolongation

4. 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

- 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

Studien-Rationale

Primary outcome:

1. 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 (Time Frame - from randomization up to 6 years):
Main Cohort

2. 4-year Progression-Free Survival (4y-PFS) by ICR according to RECIST 1.1 criteria (Time Frame - from randomization up to 5 years):
Osimertinib Cohort

Secondary outcome:

1. Progression-Free Survival (PFS) assessed by BICR per RECIST 1.1 in all randomised patients with Stage I/II NSCLC (Time Frame - from randomization up to 6 years):
Main Cohort

2. Overall Survival (OS) (Time Frame - from randomization up to 7 years):
Main Cohort

3. Maximum Plasma concentration (Cmax) (Time Frame - 12 weeks after last dose):
Main Cohort

4. Detection of ADA neutralising antibodies titers (Time Frame - up to 6 months after last dose):
Main Cohort

5. 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 - from randomization up to 7 years):
Main Cohort

6. 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):
Main Cohort

7. Time to progression (TTP) assessed by BICR according to RECIST 1.1 (Time Frame - from randomization up to 6 years):
Main Cohort

8. Time to death or distant metastasis (TTDM) assessed by BICR according to RECIST 1.1 (Time Frame - from randomization up to 6 years):
Main Cohort

9. Time from randomisation to second progression (PFS2) as defined by local standard clinical practice (Time Frame - from randomization up to 7 years):
Main Cohort

10. Trough Concentration (Ctrough) (Time Frame - up to 3 months after last dose):
Main Cohort

11. 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 3 months after last dose):
Main Cohort

12. Assessment of AEs by CTCAE v 5.0 as measures of the safety, tolerability and compliance of osimertinib with SoC SBRT therapy (Time Frame - Up to 35 days after last dose):
Osimertinib Cohort

13. WHO performance status (Time Frame - from randomization Up to 5 years):
Osimertinib Cohort

14. ECG QT interval (Time Frame - Up to 156 weeks of treatment or treatment discontinuation):
Osimertinib Cohort

15. Overall Survival (Time Frame - from randomization Up to 5 years):
Osimertinib Cohort

16. Time To Progression (TTP) (Time Frame - from randomization Up to 5 years):
Osimertinib Cohort

17. Time to CNS progression (Time Frame - from randomization Up to 5 years):
Osimertinib Cohort

18. PFS2 (Time Frame - from randomization up to 5 years):
Osimertinib Cohort

19. Site(s) of disease progression (Time Frame - from randomization up to 5 years):
Osimertinib Cohort

20. PFS by ICR using RECIST 1.1 (Time Frame - from randomization up to 5 years):
Osimertinib Cohort

Studien-Arme

  • Experimental: SoC SBRT + Durvalumab Therapy (Main Cohort)
    SBRT 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.
  • Placebo Comparator: SoC SBRT + Placebo Therapy (Main Cohort)
    SBRT Placebo (matching placebo for infusion every 4 weeks iv for up to 24 months or until progression or other discontinuation criteria are met.
  • Experimental: SoC SBRT + Osimertinib Therapy (Osimertinib cohort, single-arm, 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

Geprüfte Regime

  • Durvalumab (MEDI4736):
    Durvalumab 1500 mg every 4 weeks [q4w] intravenously [iv] for up to 24 months or until progression or other discontinuation criteria are met.
  • Placebo:
    Matching placebo for infusion every 4 weeks iv for up to 24 months or until progression or other discontinuation criteria are met.
  • Osimertinib (single-arm, open-label):
    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

Quelle: ClinicalTrials.gov


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