Durvalumab (MEDI4736) and Radiosurgery (fSRT Vs. PULSAR) for the Treatment of Non-Small Cell Lung Cancer Brain Metastases

Conditions

• Brain Metastases from Non-small Cell Lung Cancer

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Stereotactic Radiation Therapy — RADIATION
  24-27 Gy in 3 fractions- one plan, given once every other day with first cycle of Durvalumab for comparator arm. 24-27 Gy in 3 "pulses"- each pulse of radiation re-planned, given once every 4 weeks with each Durvalumab for experimental arm.
• Durvalumab — DRUG
  Durvalumab (initially developed as MEDI4736) is a human monoclonal antibody of the immunoglobulin (Ig) G1 kappa subclass that inhibits binding of PD-L1 (B7-H1, CD274) to PD-1 (CD279) and CD80 (B7-1). MEDI4736 is composed of 2 identical heavy chains and 2 identical light chains, with an overall molecular weight of approximately 149 kDa. MEDI4736 contains a triple mutation in the constant domain of the Ig G1 heavy chain that reduces binding to complement protein C1q and the fragment crystallizable gamma receptors involved in triggering effector function.

Study Details

This is a research study to find out if the new anti-cancer drug Durvalumab combined with radiation therapy to the brain will work in treating brain metastases from non-small cell lung cancer (NSCLC). Focused, highly precise radiation therapy to the brain, known as stereotactic radiosurgery (SRS), is a standard of care treatment that is commonly used for patients with metastatic lung cancer to the brain. It is standardly used as an alternative to surgery to eradicate the targeted tumours in the brain and prevent them from growing and causing symptoms. This study will look at the combination of the novel immunotherapy Durvalumab with two different ways of delivering SRS: 1) with each radiation treatment given every other day for 3 treatments with the first dose of Durvalumab (fSRT), or 2) with each radiation treatment, referred to as a "pulse," given every 4 weeks with each dose of Durvalumab for 3 treatments (PULSAR).

Key Dates

Start date

Oct 1, 2024

Status verified

Dec 2024

Primary completion

Jan 31, 2025

Completion

Jan 31, 2025

Study Design

Enrollment

0 participants (actual)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Active Comparator: Durvalumab and standard fSRT
  Fractionated stereotactic radiotherapy (fSRT) will be delivered to all previously untreated brain metastases noted at the time of treatment (up to 10 max). All brain metastases will be treated concurrently, 3 fractions total, delivered every other day (\~2 times/week) with first cycle of Durvalumab.
• Experimental: Durvalumab and PULSAR
  Personalized ultra-fractionated stereotactic adaptive radiotherapy (PULSAR), will be delivered to all previously untreated brain metastases noted at the time of treatment (up to 10 max). All brain metastases will be treated concurrently, 3 "pulses" of radiation total, delivered one pulse monthly with each cycle of Durvalumab.

Primary Outcome Measure

Intercranial clinical benefit [ Time Frame: 6 months after initiation of treatment ]