Active Surveillance for Brain Cancer

(ACTION-Brain Trial)

Overseen By Christopher Anker, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Vermont Medical Center

Must be taking: Immunotherapy, Targeted therapy

Disqualifiers: Pregnancy, Leptomeningeal disease, 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: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether some individuals with brain cancer can safely avoid radiation therapy if their brain tumors respond well to other treatments, such as immunotherapy or targeted therapy. It targets patients with brain metastases from solid tumors, including non-small cell lung cancer, who are starting or planning to start systemic therapy expected to affect the brain. Suitable candidates for this trial have at least one brain tumor not planned for immediate surgery or radiation and are about to begin treatment that can reach and act on the brain. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications. However, you must be starting or planning to start a new systemic therapy that can affect the brain, like immunotherapy or targeted therapy.

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

Previous studies have shown that treatments working throughout the body, such as immunotherapy and targeted therapy, have promising safety results for patients with cancer that has spread to the brain. Research on HER2-positive brain metastases found that treatments like trastuzumab were well-tolerated and effective in the brain. Specifically, one study showed that 71% of patients experienced noticeable improvement without major safety concerns.

While these treatments are generally safe, individual reactions can vary. Some people may experience side effects like tiredness or nausea, but serious problems are less common. Prospective participants should discuss possible risks and benefits with a doctor. This trial aims to avoid using radiation, so understanding the safety of these body-wide treatments is crucial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about active surveillance for brain cancer because it offers a non-invasive approach that relies on regular monitoring instead of immediate invasive treatments like surgery or radiation. This method involves using systemic therapies, such as immunotherapy or targeted agents, only when necessary, allowing patients to avoid the side effects of radiation unless their condition worsens. By focusing on regular MRI check-ups and using radiation only if progression is observed, this approach could lead to better quality of life for patients while still effectively managing the disease.

What evidence suggests that active surveillance could be effective for brain metastases?

Research has shown that systemic therapies, which work throughout the body, hold promise for treating cancer that has spread to the brain. In this trial, participants with brain metastases will receive standard-of-care systemic therapy expected to have intracranial activity, such as immunotherapy, targeted therapy, or anti-HER2 agents. One study found that 58.9% of patients receiving these treatments did not experience cancer progression for at least 12 months. Another study showed similar results, with 61.6% of patients maintaining stable disease for 12 months and 71% experiencing significant improvement in brain tumors. These treatments can cross into the brain and have been particularly effective for certain types of cancer, like HER2-positive cancers. By using MRI scans to monitor progress and continuing these treatments, some patients in this trial may avoid radiation therapy if their condition remains stable. ^{1 3 4 6 7}

Who Is on the Research Team?

Randall Holcombe, MD, MBA

Principal Investigator

University of Vermont Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with brain metastases from lung cancer or other solid tumors, who are starting treatments expected to cross into the brain. They must have at least one brain tumor not scheduled for radiation/surgery and be able to undergo MRI scans.

Inclusion Criteria

I was diagnosed with a solid tumor cancer within the last 5 years.

Ability to obtain MRI head scans with contrast

Ability to understand and sign a written informed consent

Exclusion Criteria

Pregnant or nursing individuals

Serious medical comorbidities that would prevent study participation

I haven't started any new cancer treatments in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Systemic Therapy Initiation

Participants initiate systemic therapy expected to penetrate the blood-brain barrier and achieve intracranial activity

4-8 weeks

1 visit (in-person) for MRI re-evaluation

Surveillance

Participants undergo structured surveillance with MRIs every 3 months to monitor brain metastases

Up to 2 years

MRI every 3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Active Surveillance

Trial Overview The study tests if certain patients can skip radiation therapy after their brain tumors respond well to systemic therapies like immunotherapy, targeted therapy, or chemotherapy. It involves regular MRIs to monitor tumor response.

How Is the Trial Designed?

Group I: Systemic Therapy With Surveillance for Brain Metastases Experimental Treatment 1 Intervention

Participants with brain metastases from solid tumors will receive standard-of-care systemic therapy expected to have intracranial activity, such as immunotherapy, targeted therapy, or anti-HER2 agents. A re-evaluation brain MRI will be performed 4-8 weeks after starting therapy. If lesions are stable or responding, patients will continue on systemic therapy with MRI surveillance every 3 months. Radiation therapy may be administered only if progression is observed. All participants are managed according to this pathway, regardless of primary tumor type.

Who Is Running the Clinical Trial?

University of Vermont Medical Center

Lead Sponsor

Trials

46

Recruited

25,900+

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S2468294225001339

Systemic therapy breakthroughs in the management of ... This treatment is based on the HER2CLIMB trial, in which the 1-year CNS progression-free survival (PFS) rate was estimated at 40.2 % [9,10]. Another tucatinib- ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11959222/

Anti‑HER2‑targeted therapies for the treatment of advanced ... Various anti-HER2 targeted therapies have brought both new opportunities and challenges to patients with HER2-positive BCBM over the past decade.

3. onclive.com onclive.com/view/systemic-therapies-are-now-preferred-in-some-patients-with-her2-breast-cancer-brain-metastases

Systemic Therapies Are Now Preferred in Some Patients ... In those with baseline brain metastases, the median progression-free survival (PFS) was 17.3 months. The 12-month CNS PFS was 58.9%.

4. ascopubs.org ascopubs.org/doi/10.1200/OP.23.00794

Breast Cancer Brain Metastasis: A Comprehensive Review Currently, multiple studies of systemic therapy for HER2 positive BCBMs has been published (Table 2). Trastuzumab monotherapy showed survival ...

5. dana-farber.org dana-farber.org/newsroom/news-releases/2024/antibody-drug-conjugate-found-effective-against-brain-metastases-in-patients-with-her2-positive-breast-cancer

Antibody-drug conjugate found effective against brain ... 12- month progression-free survival was 61.6%. Seventy-one percent of participants had an intracranial objective response – a measurable ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8230933/

Brain Metastases in HER2-Positive Breast Cancer Trastuzumab's combination with WBRT in a small cohort of 31 patients appeared to be safe and effective, with an intracranial ORR of 74.2% and a median time to ...

7. nature.com nature.com/articles/s41523-021-00235-7

Outcomes of changing systemic therapy in patients with ... Among the 2645 patients with BC and BMs treated between 2002 and 2015, 74 were included for analysis. 40.5% of patients had HER2 + disease.