Whole-Brain Radiation Therapy for Small Cell Lung Cancer

Not currently recruiting at 308 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: NRG Oncology

Disqualifiers: CNS metastases, Hydrocephalus, Invasive malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 10

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether whole-brain radiation therapy is more effective with or without avoiding the hippocampus, a brain region crucial for memory, in patients with small cell lung cancer. The goal is to determine if this approach can treat cancer effectively while minimizing side effects on memory and thinking. Patients with doctor-confirmed small cell lung cancer who have completed chemotherapy might be suitable candidates for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to significant advancements in cancer care.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, planned concurrent chemotherapy during the trial is not allowed, except for atezolizumab, which is permitted.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that whole-brain radiation therapy with hippocampal avoidance (HA-PCI) is considered safe. Some studies suggest that avoiding the hippocampus during radiation can help protect memory and thinking skills. However, the overall effects on brain function remain unclear, as some studies show mixed results.

One study found that HA-PCI helps preserve parts of the brain important for thinking and memory, potentially causing fewer memory problems than whole-brain radiation without hippocampal avoidance.

In summary, while HA-PCI appears safe, more research is needed to fully understand its long-term impact on memory and thinking. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these radiation therapy approaches for small cell lung cancer because they offer innovative strategies to protect healthy brain tissue while targeting cancer cells. Unlike traditional whole-brain radiation therapy, which can affect the entire brain, PCI with hippocampal avoidance (HA) using intensity-modulated radiation therapy (IMRT) aims to minimize damage to the hippocampus, a region crucial for memory, potentially reducing cognitive side effects. Meanwhile, the use of prophylactic cranial irradiation (PCI) with three-dimensional conformal radiation therapy (3DCRT) offers a precise targeting method, which may improve the overall safety and effectiveness of the treatment. These advancements could lead to better quality of life for patients by decreasing the risk of cognitive decline commonly associated with whole-brain radiation.

What evidence suggests that this trial's treatments could be effective for small cell lung cancer?

Research has shown that whole-brain radiation therapy, a treatment in this trial, can effectively kill cancer cells and shrink tumors in small cell lung cancer. This trial compares two approaches: one arm receives prophylactic cranial irradiation (PCI) using three-dimensional conformal radiation therapy (3DCRT), while the other receives PCI with hippocampal avoidance using intensity-modulated radiation therapy (IMRT). Studies have found that avoiding the hippocampus, a part of the brain, during therapy can lower the risk of memory and thinking problems. This method, known as hippocampal avoidance, may lead to fewer memory-related side effects. However, it remains unclear if it is more effective than regular radiation therapy in treating cancer. More research is needed to determine if hippocampal avoidance provides better overall results for patients. ^{4 6 7 8 9}

Who Is on the Research Team?

Vinai Gondi

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

This trial is for adults with small cell lung cancer who've responded to chemotherapy, can undergo MRI scans, and agree to use contraception. It's not for those with prior head/neck radiation (except T1 glottic cancer), CNS metastases, severe comorbidities, other recent cancers (except skin cancer), or untreated HIV.

Inclusion Criteria

I finished my chemotherapy between 1 to 8 weeks ago.

I have extensive-stage small cell lung cancer and may get chest radiation after chemotherapy.

My small cell lung cancer is classified as either limited or extensive stage.

Exclusion Criteria

You cannot have a magnetic resonance imaging (MRI) scan if you have metal implants or severe claustrophobia.

I have had radiotherapy to my head or neck, excluding T1 glottic cancer, with overlapping radiation fields.

I will receive chemotherapy or cancer drugs during my brain radiation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients undergo prophylactic cranial irradiation (PCI) with or without hippocampal avoidance for 2 weeks, 5 fractions per week

2 weeks

10 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-ups every 3 months for 1 year, then every 6 months until 3 years, and annually thereafter

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Hippocampal Avoidance
• Whole-Brain Radiation Therapy

Trial Overview

The study compares whole-brain radiation therapy effectiveness with and without avoiding the hippocampus—a brain area linked to memory—to see if it reduces cognitive side effects while treating lung cancer that is limited stage or has spread extensively.

How Is the Trial Designed?

Group I: PCI with HA using IMRT Experimental Treatment 1 Intervention

PCI with hippocampal avoidance (HA) using intensity-modulated radiation therapy (IMRT) for 2 weeks, 5 fractions/week.

Group II: PCI using 3DCRT Active Control 1 Intervention

Prophylactic cranial irradiation (PCI) using three-dimensional conformal radiation therapy (3DCRT) for 2 weeks, 5 fractions/week.

Who Is Running the Clinical Trial?

NRG Oncology

Lead Sponsor

Trials

242

Recruited

105,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Radiation Therapy Oncology Group

Collaborator

Trials

191

Recruited

64,900+

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10626474/

Cranial radiation therapy with hippocampus avoidance in ...

HA-CRT appears to be safe in lung cancer, but it may not outperform conventional CRT. Larger RCTs comparing HA-CRT and CRT are warranted.

2.

ascopubs.org

ascopubs.org/doi/abs/10.1200/JCO-25-00221

Randomized Phase II/III Trial NRG-CC003

Hippocampal avoidance (HA) during therapeutic whole-brain radiotherapy reduces the risk of neurocognitive function (NCF) toxicity in ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02635009

Study Details | NCT02635009 | Whole-Brain Radiation ...

Avoiding the hippocampus during whole-brain radiation could decrease the chance of side effects on memory and thinking. It is not yet known whether giving whole ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12342643/

Randomized Phase II/III Trial NRG-CC003 - PMC

Hippocampal avoidance (HA) during therapeutic whole-brain radiotherapy reduces the risk of neurocognitive function (NCF) toxicity in brain ...

5.

sciencedirect.com

sciencedirect.com/science/article/pii/S2452109425000089

National Trends in Radiation Treatment for Small Cell Lung ...

Kaplan–Meier curves depicting estimates of survival for patients treated with whole brain radiation therapy (WBRT), hippocampal avoidance WBRT (HA-WBRT), and ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9066538/

Impact of Hippocampal Avoidance - Prophylactic Cranial ...

HA-PCI is safe, yet its effect on neurocognition and imaging remains unclear, as studies have shown contradictory results.

7.

sciencedirect.com

sciencedirect.com/science/article/pii/S2667005423000297

Quality assurance and safety of hippocampal avoidance ...

Small cell lung cancer (SCLC) accounts for about 14% of all lung carcinomas worldwide, and has a 60% risk of progressing to distant organs, primarily the liver, ...

8.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39718983/

Hippocampal avoidance prophylactic cranial irradiation ...

Hippocampal avoidance prophylactic cranial irradiation (HA-PCI) for small-cell lung cancer better preserves white matter networks compared to ...

9.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0169500224005701

Impact of HA-PCI on self-reported cognitive functioning and ...

HA-PCI reduces self-reported cognitive impairment at 4-months. HA-PCI does not improve longitudinal self-reported cognitive functioning over time.