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
a study on Lung Cancer Non-Small Cell Lung Cancer Lung Tumor
Summary
- Eligibility
- for people ages 18-130 (full criteria)
- Location
- at Los Angeles, California and other locations
- Dates
- study startedcompletion around
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 with Stage I/II lymph node negative NSCLC and confirmed to meet all eligibility criteria will be randomized 1:1 to receive either Durvalumab + SoC SBRT or placebo + SoC SBRT.
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-TKI sensitizing 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 4-year 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, Medically Inoperable, Operable with Patient refusal, SBRT, SABR, EGFR, Lung Neoplasms, Non-Small-Cell Lung Carcinoma, (Osimertinib cohort, single-arm, open-label separate cohort)
Eligibility
For people ages 18-130
Main Cohort Key Inclusion Criteria:
- Age ≥18 years
- Planned SoC SBRT as definitive treatment
- World Health Organization (WHO)/ECOG PS of 0, 1 or 2
- Life expectancy of at least 12 weeks
- Body weight >30 kg
- Submission of tumor tissue sample if available
- Adequate organ and marrow function required
- Patients with central or peripheral lesions are eligible
- Staging studies must be done during screening (PET-CT within 10 weeks)
- Patients with a history of metachronous NSCLC and synchronous lesions are eligible with some exceptions
Main Cohort Key Exclusion Criteria:
- Mixed small cell and non-small cell cancer
- History of allogeneic organ transplantation
- History of another primary malignancy with exceptions
- History of active primary immunodeficiency
- 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
- Prior exposure to immune-mediated therapy with exceptions
Osimertinib Cohort Key Inclusion Criteria
- Age ≥18 years
- Planned SoC SBRT as definitive treatment
- WHO/ECOG PS of 0, 1, or 2
- Patients with central or peripheral lesions are eligible
- Patients with a history of metachronous NSCLC and synchronous lesions are eligible with some exceptions
- Staging studies must be done during screening (PET-CT within 10 weeks)
- Submission of tumor tissue sample if available
- 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)
- Adequate bone marrow reserve or organ function required
- Female patients should be using highly effective contraceptive measures
- 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
- Mixed small cell and non-small cell cancer
- Patients with known or increased risk factor for QTc prolongation
- 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
- 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
Locations
- Research Site
Los Angeles California 90095 United States - Research Site
Long Beach California 90806 United States - Research Site
Duarte California 91010 United States
Details
- Status
- in progress, not accepting new patients
- Start Date
- Completion Date
- (estimated)
- Sponsor
- AstraZeneca
- Links
- Lung Cancer Study Locator details (for US)
- ID
- NCT03833154
- Phase
- Phase 3 research study
- Study Type
- Interventional
- Participants
- About 724 people participating
- Last Updated