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)

Phase 3

Recruiting

• Conditions: non small-cell lung cancer; lung cancer; 10038666

• Registration Number: NL-OMON54495
• Lead Sponsor: Astra Zeneca

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 9 September 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 8

Inclusion Criteria

Main cohort:
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 sample
8. Adequate organ and marrow function required
9. Patients with central or peripheral lesions are eligible
10. Staging must be done within 10 weeks before randomization (PET)
11. Pulmonary Function Testing within 12 weeks of randomization
12. Patients with a history of metachronus stage I/II (T1-T3N0M0) NSCLC treated
definitely with surgery only or SBRT only > 1 yr prior to enrolment are eligible
Osimertinib cohort:
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 sample
8. Adequate organ and marrow function required
9. Patients with central or peripheral lesions are eligible
10. Staging must be done within 10 weeks before randomization (PET)
11. Pulmonary Function Testing within 12 weeks of randomization
12. Patients with a history of metachronus stage I/II (T1-T3N0M0) NSCLC treated
definitely with
13. Local confirmation of EGFR mutation (Ex19del and/or L858R)

Exclusion Criteria

Main cohort:
1. Mixed small cell and non-small cell cancer histology
2. History of allogeneic organ transplantation
3. History of another primary malignancy with exceptions
4. History of active primary immunodeficiency
5. Uncontrolled intercurrent illness (patients with controlled chronic
obstructive pulmonary disease are allowed)
6. Known allergy or hypersensitivity to any of the drugs or any of the study
drug excipients
7. Prior exposure to immune-mediated therapy including, but not limited to,
other anti-CTLA-4, anti-PD-1, anti-PD-L1, and anti-programmed cell death ligand
2
antibodies, excluding therapeutic anticancer vaccines
8. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer
treatment. Concurrent use of hormonal therapy for non-cancer-related conditions
(eg, hormone replacement therapy) is acceptable. If patient has been on
adjuvant hormonal treatment for early stage breast cancer for more than 5
years, and there is no evidence of recurrence, then patient is eligible with
study physician discussion.
9. Major surgical procedure within 28 days prior to first dose of IP
10. Current or prior use of immunosuppressive medication within 14 days before
the first dose of IP.
11. Positive pregnancy test for pre-menopausal women
12. local confirmation of EGFR mutation (Ex19del and/or L858R)

Osimertinib cohort:
1. Mixed small cell and non-small cell cancer histology
2. Treatment with any of the following:
- Preoperative (neoadjuvant) or adjuvant platinum-based or other chemotherapy
for
the disease under investigation;
- Any prior anticancer or immunological therapy, including investigational
therapy,
for treatment of NSCLC for the disease under investigation;
- Prior treatment with neoadjuvant or adjuvant EGFR-TKI;
3. History of another primary malignancy with exceptions
4. Sever or uncontrolled systemic disease.
5. Refractory nausea and vomiting, chronic GI diseases, inability to swallow the
formulated product, or previous significant bowel resection that would preclude
adequate absorption of osimertinib;
6. Any of the following cardiac criteria:
- Mean resting QTc > 470 msec obtained from 3 electrocardiograms (ECGs), using
the screening clinic ECG machine-derived QTcF value;
- Any clinically important abnormalities in rhythm, conduction, or morphology of
resting ECG
- Patient with any factors that increase the risk of QTc prolongation or risk of
arrhythmic events, such as electrolyte abnormalities
7. Past medical history of ILD, drug-induced ILD, or any evidence of clinically
active ILD;

8. History of hypersensitivity to active or inactive excipients of osimertinib
or drugs withva similar chemical structure or class to osimertinib;

Study & Design

• Study Type: Interventional
• Study Design: Not specified