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

Recruiting at 483 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

Trial Summary

What is the purpose of this trial?

This phase III trial studies magnetic resonance imaging (MRI) surveillance and prophylactic cranial irradiation (PCI) to see how well they work compared to MRI surveillance alone in treating patients with small cell lung cancer. MRI scans are used to monitor the possible spread of the cancer with an MRI machine over time. PCI is radiation therapy that is delivered to the brain in hopes of preventing spread of cancer into the brain. The use of brain MRI alone may reduce side effects of receiving PCI and prolong patients' lifespan. Monitoring with MRI scans alone (delaying radiation until the actual spread of the cancer) may be at least as good as the combination of PCI with MRI scans.

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.

What data supports the effectiveness of the treatment Magnetic Resonance Imaging, Lumakras, Vectibix, Prophylactic Cranial Irradiation, PCI, Prophylactic Cranial Irradiation, Brain Radiation Therapy for small cell lung cancer?

Research shows that prophylactic cranial irradiation (PCI) can improve survival and reduce the risk of cancer spreading to the brain in patients with small cell lung cancer, especially when combined with modern MRI brain screening to ensure no existing brain metastases. ^{1 2 3 4 5}

Is prophylactic cranial irradiation (PCI) safe for small cell lung cancer patients?

Prophylactic cranial irradiation (PCI) is generally considered safe for small cell lung cancer patients, but it can be associated with neurotoxicity (damage to the nervous system). ^{4 5 6 7 8}

How is prophylactic cranial irradiation (PCI) different from other treatments for small cell lung cancer?

Prophylactic cranial irradiation (PCI) is unique because it is a preventive brain radiation therapy used to reduce the risk of cancer spreading to the brain in small cell lung cancer patients, even when no brain metastases are detected. Unlike other treatments that target existing tumors, PCI is used as a precautionary measure, often in conjunction with regular brain imaging like MRI to monitor for any changes. ^{1 4 5 7 9}

Research Team

Chad G Rusthoven

Principal Investigator

SWOG Cancer Research Network

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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 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 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]

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 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]

References

1. England 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. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Prophylactic cranial irradiation for limited-stage small-cell lung cancer in the magnetic resonance imaging era. [2023]

3. United States 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. [2022]

4. France pubmed.ncbi.nlm.nih.gov

[The role of prophylactic cranial irradiation in small cell lung cancer]. [2021]

5. United States 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. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Limited-Stage Small Cell Lung Cancer: Is Prophylactic Cranial Irradiation Necessary? [2020]

7. Ireland pubmed.ncbi.nlm.nih.gov

Prophylactic cranial irradiation for extensive-stage small cell lung cancer: Analysis based on active brain MRI surveillance. [2022]

8. England 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. [2022]

9. Israel pubmed.ncbi.nlm.nih.gov

Stereotactic Radiosurgery for Brain Metastases in Small Cell Lung Cancer: The Davidoff Cancer Center Experience. [2020]