Summary

Eligibility
for people ages 18-130 (full criteria)
Location
at UCLA
Dates
study started
estimated completion

Description

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. An additional cohort will assess Osimertinib following SBRT in patients with early stage unresected T1 to T3N0M0 NSCLC harbouring an EGFR mutation.

Official 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

Details

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.

Keywords

Carcinoma, Non-Small-Cell Lung, NSCLC, Early-Stage NSCLC, Lung cancer, Double- Blind, PD-L1, MEDI4736, Durvalumab, Osimertinib, PFS, OS, Unresected lung cancer, Inoperable, Operable, SBRT, SABR, EGFR, Lung Neoplasms, Osimertinib (single-arm, open-label)

Eligibility

For people ages 18-130

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:
  5. Preoperative or adjuvant platinum-based or other chemotherapy for the disease under investigation
  6. Prior treatment with neoadjuvant or adjuvant EGFR TKI
  7. 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
  8. 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
  9. Any of the following cardiac criteria
  10. Mean resting corrected QT interval >470 msec, obtained from 3 ECGs
  11. Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG.
  12. 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
  13. Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD

Locations

  • Research Site accepting new patients
    Los Angeles California 90095 United States
  • Research Site accepting new patients
    La Jolla California 92037 United States
  • Research Site not yet accepting patients
    Newport Beach California 92663 United States
  • Research Site accepting new patients
    San Diego California 92123 United States
  • Research Site withdrawn
    Sacramento California 95816 United States
  • Research Site currently not accepting new patients, but might later
    Los Angeles California 90073 United States
  • Research Site accepting new patients
    Long Beach California 90806 United States
  • Research Site terminated
    Duarte California 91010 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
AstraZeneca
ID
NCT03833154
Phase
Phase 3 research study
Study Type
Interventional
Participants
Expecting 733 study participants
Last Updated