MRI Monitoring vs. Preventive Brain Radiation for Small Cell Lung Cancer

Recruiting at 499 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: SWOG Cancer Research Network

Disqualifiers: Brain metastases, Severe hepatic disease, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 13

Duration: 2 weeks for PCI, up to 24 months for MRI

668 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if using MRI scans alone is as effective as combining them with preventive brain radiation (Prophylactic Cranial Irradiation) for treating small cell lung cancer. The goal is to monitor potential brain spread and assess if delaying radiation reduces side effects while controlling the cancer. Participants are divided into two groups: one will receive regular MRI scans, and the other will receive both MRI scans and preventive radiation. Ideal candidates for this trial have small cell lung cancer, no current brain involvement, and have completed initial therapy. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It mentions that immunotherapy can be continued at the discretion of your doctor, so it's best to discuss your specific medications with your healthcare provider.

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

Research has shown that using MRI scans to monitor small cell lung cancer is safe. MRI, a non-invasive method, uses magnets and radio waves to capture images of the body's interior. It does not involve radiation, so it typically has fewer side effects than treatments that do.

Prophylactic cranial irradiation (PCI) is a type of radiation therapy that helps prevent cancer from spreading to the brain. Studies have found that PCI can extend the lives of small cell lung cancer patients. However, because it involves radiation, it can cause side effects like tiredness, headaches, or problems with thinking and memory.

Overall, MRI monitoring is well-tolerated and carries minimal risks, making it a safe choice. PCI is effective but may cause more side effects due to the radiation. When considering joining a trial, it is important to weigh the potential benefits and risks of each treatment option. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it compares two approaches for managing small cell lung cancer (SCLC) with a focus on the brain. Traditionally, Prophylactic Cranial Irradiation (PCI) is used to prevent cancer spread to the brain, but it can cause side effects like memory problems. This trial explores whether regular MRI monitoring can be an effective alternative to PCI, potentially reducing unnecessary radiation exposure and associated side effects. By comparing MRI scans to conventional PCI, researchers hope to find a way to protect the brain without compromising patient quality of life.

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

This trial will compare MRI monitoring with preventive brain radiation, known as prophylactic cranial irradiation (PCI), for patients with small cell lung cancer. Research has shown that PCI can increase survival rates and lower the risk of cancer spreading to the brain. In this trial, some participants will receive PCI along with regular MRI scans. Others will undergo MRI scans alone at specified intervals to monitor the disease. Recent improvements in MRI technology make it easier to detect and track cancer, potentially allowing for effective monitoring without the side effects of preventive radiation. While PCI has proven benefits, MRI offers an alternative that may help avoid unnecessary treatments. ^{4 5 6 7 8}

Who Is on the Research Team?

Chad G Rusthoven

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

This trial is for adults with small cell lung cancer (SCLC) who've responded to first-line therapy without disease progression. They must have good organ function, no metal implants or allergies that make MRI unsafe, and not be receiving treatment for other cancers. HIV-positive patients can join if treated and stable. Pregnant women are excluded, and participants must agree to use contraception.

Inclusion Criteria

I have not had radiation therapy to the brain.

HIV testing is not required for eligibility for this protocol

I've had a brain MRI recently showing no brain metastases or leptomeningeal disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients undergo conventional or hippocampal avoidance PCI over 20 minutes 5 days per week for 2 weeks, and MRI scans at 3, 6, 9, 12, 18, and 24 months

2 weeks for PCI, up to 24 months for MRI

PCI: 10 visits (in-person), MRI: 6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments for adverse events and cognitive function

Up to 2 years

Assessments at 3, 6, 9, 12, 18, and 24 months

What Are the Treatments Tested in This Trial?

Interventions

• Magnetic Resonance Imaging
• Prophylactic Cranial Irradiation

Trial Overview The study compares two approaches: one group will be monitored with brain MRIs alone, while the other will receive preventive brain radiation plus MRI monitoring. The goal is to see if avoiding early radiation can extend life without increasing cancer spread risks.

How Is the Trial Designed?

Group I: Arm II (MRI) Experimental Treatment 1 Intervention

Patients undergo MRI scan at 3, 6, 9, 12, 18, and 24 months.

Group II: Arm I (PCI, MRI) Active Control 2 Interventions

Patients undergo conventional or hippocampal avoidance PCI over 20 minutes 5 days per week for 2 weeks. Patients also undergo MRI scan at 3, 6, 9, 12, 18, and 24 months.

Prophylactic Cranial Irradiation is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Prophylactic Cranial Irradiation for:

• Small cell lung cancer
• Limited stage small cell lung cancer
• Extensive stage small cell lung cancer

Approved in United States as Prophylactic Cranial Irradiation for:

• Small cell lung cancer
• Limited stage small cell lung cancer
• Extensive stage small cell lung cancer

Approved in Canada as Prophylactic Cranial Irradiation for:

• Small cell lung cancer
• Limited stage small cell lung cancer
• Extensive stage small cell lung cancer

Approved in Japan as Prophylactic Cranial Irradiation for:

• Small cell lung cancer
• Limited stage small cell lung cancer
• Extensive stage small cell lung cancer

Who Is Running the Clinical Trial?

SWOG Cancer Research Network

Lead Sponsor

Trials

403

Recruited

267,000+

Southwest Oncology Group

Lead Sponsor

Trials

389

Recruited

260,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Prophylactic cranial irradiation (PCI) significantly reduced the brain relapse rate in patients with small-cell lung cancer (SCLC) who achieved a complete response to treatment, with rates dropping from 37% to 9% in limited disease patients and from 31% to 8% in extensive disease patients.

Despite the reduction in brain relapses, PCI did not improve overall survival rates for SCLC patients, and severe CNS toxicity occurred in about 3% of those treated, indicating that while PCI may help prevent brain metastases, its impact on survival remains unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prophylactic cranial irradiation in complete responders with small-cell lung cancer: analysis of the Mayo Clinic and North Central Cancer Treatment Group data bases. Shaw, EG., Su, JQ., Eagan, RT., et al.[2022]

Prophylactic cranial irradiation (PCI) significantly improves overall survival in patients with limited-stage small-cell lung cancer (SCLC), with a 2-year survival rate of 50% for those receiving PCI compared to 29% for those who did not.

In contrast, PCI does not show a significant survival benefit for patients with extensive-stage SCLC, indicating that the effectiveness of PCI may depend on the stage of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival impact of prophylactic cranial irradiation in small-cell lung cancer in the modern era of magnetic resonance imaging staging. Lim, YJ., Song, C., Kim, HJ.[2022]

In a study of 92 patients with limited stage small cell lung cancer (LS-SCLC), prophylactic cranial irradiation (PCI) was associated with improved progression-free survival (PFS), showing a median PFS of 26.3 months with PCI compared to 12.3 months without it.

Patients who achieved a complete response to initial therapy did not benefit from PCI in terms of PFS, suggesting that modern imaging may allow some LS-SCLC patients to avoid PCI without compromising their outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Limited-Stage Small Cell Lung Cancer: Is Prophylactic Cranial Irradiation Necessary? Farris, MK., Wheless, WH., Hughes, RT., et al.[2020]

In a study of 10 small cell lung cancer patients with brain metastases treated with stereotactic radiosurgery (SRS), the intracranial objective response rate (iORR) was 57%, indicating a significant response to treatment.

The median overall survival after SRS was 23.2 months, suggesting that MRI surveillance combined with SRS could be an effective alternative to prophylactic cranial irradiation (PCI) in managing brain metastases in SCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Radiosurgery for Brain Metastases in Small Cell Lung Cancer: The Davidoff Cancer Center Experience. Dudnik, E., Allen, AM., Michaeli, N., et al.[2020]

In a retrospective study of 150 untreated small cell lung cancer (SCLC) patients who received brain imaging, only 75 were potentially eligible for prophylactic cranial irradiation (PCI), and 13 experienced isolated brain recurrences as their first progression site.

The study found no significant survival benefit from PCI in patients who underwent systematic brain imaging, suggesting that PCI may have a limited impact on overall survival and prevention of isolated brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The role of prophylactic cranial irradiation in small cell lung cancer]. Fievet, L., Sculier, JP., Meert, AP., et al.[2021]

Prophylactic cranial irradiation (PCI) significantly improved neurological survival and reduced the incidence of brain metastases in patients with limited stage small cell lung cancer (LS-SCLC) who responded to initial therapy, as shown in a study of 243 patients.

While PCI did not lead to an overall survival benefit, it was associated with a notable decrease in the risk of neurological death, highlighting its importance in managing intracranial progression in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utility of Prophylactic Cranial Irradiation for Limited Stage Small Cell Lung Cancer in the Modern Era with Magnetic Resonance Imaging Surveillance. Ghanta, S., Keller, A., Rodríguez-López, JL., et al.[2021]

In a study of 80 patients with limited-disease small-cell lung cancer (LD-SCLC) who had no brain metastases confirmed by MRI, prophylactic cranial irradiation (PCI) did not show a significant survival benefit compared to those who did not receive PCI, with median overall survival times of 4.3 years for the PCI group and not reached for the non-PCI group.

The study found no significant differences in progression-free survival or the cumulative incidence of brain metastases between the PCI and non-PCI groups, suggesting that PCI may not be necessary for patients with LD-SCLC who have responded well to initial therapy and have no brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of prophylactic cranial irradiation in patients with limited-disease small-cell lung cancer who were confirmed to have no brain metastasis via magnetic resonance imaging after initial chemoradiotherapy. Mamesaya, N., Wakuda, K., Omae, K., et al.[2022]

In a study of 118 patients with extensive-stage small-cell lung cancer (ES-SCLC) who responded to first-line chemotherapy, prophylactic cranial irradiation (PCI) significantly improved both progression-free survival (PFS) and overall survival (OS) compared to those who did not receive PCI.

Among patients who did not receive PCI, nearly 47.4% developed brain metastases within the first year, highlighting the potential benefit of PCI in preventing this complication under active brain MRI surveillance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prophylactic cranial irradiation for extensive-stage small cell lung cancer: Analysis based on active brain MRI surveillance. Yu, J., Ouyang, W., Yang, Y., et al.[2022]

In a study of 116 patients with limited-stage small-cell lung cancer (LS-SCLC), those who received prophylactic cranial irradiation (PCI) after achieving a complete response (CR) showed significantly better overall survival (52.5% vs. 35.1%) and progression-free survival (45.0% vs. 28.2%) compared to those who did not receive PCI.

Patients with a partial response (PR) did not benefit from PCI, indicating that the effectiveness of PCI is closely linked to the initial tumor response, emphasizing the importance of selecting patients based on their treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prophylactic cranial irradiation for limited-stage small-cell lung cancer in the magnetic resonance imaging era. Pan, L., Fan, X., Wang, L., et al.[2023]

Citations

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Efficacy evaluation of prophylactic cranial irradiation for ... Collectively, the results of the present study demonstrated that PCI remained effective in improving OS and reducing the rate of BM in patients ...

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Re-examining prophylactic cranial irradiation in small cell ... In this meta-analysis, PCI was associated with improved overall survival and reduced cumulative incidence of brain metastases in patients with SCLC, ...

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Rates of Overall Survival and Intracranial Control in the ... These findings suggest that patients with LS-SCLC staged with MRI who undergo PCI after thoracic radiation treatment were not associated with a decreased risk ...

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Rates of Overall Survival and Intracranial Control in ... - PubMed Rates of Overall Survival and Intracranial Control in the Magnetic Resonance Imaging Era for Patients With Limited-Stage Small Cell Lung Cancer ...