Berzosertib + Radiation for Brain Metastases from Lung Cancer

Not currently recruiting at 9 trial locations
Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: National Cancer Institute (NCI)
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose and assess the side effects of berzosertib, an experimental treatment, when combined with whole-brain radiation therapy for lung cancer that has metastasized to the brain. Berzosertib may inhibit tumor cell growth, while radiation uses x-rays to destroy cancer cells. The trial involves two groups: one receiving berzosertib with radiation and the other undergoing surgery in addition to these treatments. It seeks participants with lung cancer that has spread to the brain, who require symptom relief and can identify if they experience frequent seizures or need brain surgery. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop all current medications, but it does mention that ongoing phenytoin should be discontinued or switched to another medication with an 8-day washout period before starting the trial. Also, strong inhibitors or inducers of CYP3A4 should be avoided, and dexamethasone should be reduced to 8 mg or less per day if possible.

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

Research has shown that berzosertib, when combined with treatments like cisplatin, is usually well-tolerated by patients with advanced solid tumors. This suggests it might also be safe to use with radiation therapy. However, as this combination is new, the study aims to determine the best dose and monitor for any side effects.

Whole-brain radiotherapy is a common and generally safe treatment for cancer that has spread to the brain. Although it can cause some changes in thinking and memory, it remains a standard method for treating brain tumors.

The trial tests these treatments together to ensure they are effective and safe. Currently in its early stages, the trial focuses on understanding the safety and correct dosage of this combination.12345

Why are researchers excited about this trial's treatments?

Most treatments for brain metastases from lung cancer, like standard whole-brain radiotherapy, focus on broadly targeting cancerous areas. But berzosertib works differently, targeting a specific enzyme called ATR, which plays a critical role in repairing damaged DNA in cancer cells. By inhibiting ATR, berzosertib may make cancer cells more susceptible to radiation, potentially enhancing the effectiveness of the treatment. Researchers are excited because this combined approach could improve outcomes by making tumors less able to repair themselves, offering a new strategy that complements existing treatments.

What evidence suggests that this trial's treatments could be effective for brain metastases from lung cancer?

Research has shown that berzosertib, also known as M6620, can enhance the effectiveness of radiation therapy for treating lung cancer that has spread to the brain. Early studies demonstrated that berzosertib aids radiation in halting tumor growth by blocking certain proteins essential for cancer cell growth. In this trial, participants in Group I will receive whole-brain radiotherapy with berzosertib. Whole-brain radiotherapy is already known to shrink brain tumors. Participants in Group II will receive berzosertib before surgery, followed by whole-brain radiotherapy and additional berzosertib treatment. Together with berzosertib, these treatments might more effectively prevent cancer from worsening.23678

Who Is on the Research Team?

PM

Pranshu Mohindra

Principal Investigator

Mayo Clinic Cancer Center LAO

Are You a Good Fit for This Trial?

Adults with non-small cell lung cancer, small cell lung cancer, or neuroendocrine tumors that have spread to the brain. They must be fit for whole brain radiation therapy and not pregnant or breastfeeding. Participants need functioning kidneys, a stable blood count, and agree to use contraception. Those who've had recent chemotherapy or certain treatments are excluded.

Inclusion Criteria

You are expected to live for more than two months so that you can finish the study treatment and be checked for any harmful effects.
I have lung cancer with brain metastases and am considering palliative brain radiation.
Your white blood cell count is at least 3,000 per microliter.
See 10 more

Exclusion Criteria

I am allergic to medications similar to M6620.
I do not have genetic conditions like Li Fraumeni syndrome or ataxia telangiectasia.
I am not taking strong CYP3A4 inhibitors or inducers, and can change my epilepsy medication if needed.
See 8 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive berzosertib intravenously and undergo whole-brain radiation therapy. Group I receives radiation 5 days a week for 15 fractions over 3 weeks, while Group II receives berzosertib prior to surgery followed by radiation as in Group I.

3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-ups every 2 months for 6 months, every 3-4 months for another 6 months, then every 6 months for 1 year.

24 months

What Are the Treatments Tested in This Trial?

Interventions

  • Berzosertib (M6620 [VX-970])
  • Whole-Brain Radiotherapy
Trial Overview The trial is testing berzosertib combined with whole brain radiation therapy against standard care for patients with specific types of lung cancer that has spread to the brain. The goal is to find out if this combination works better than current treatments.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Group I: Group II (VX-970, surgery, whole-brain radiation therapy)Experimental Treatment4 Interventions
Group II: Group I (VX-970, whole-brain radiation therapy)Experimental Treatment3 Interventions

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials
14,080
Recruited
41,180,000+

Published Research Related to This Trial

In a study of 518 patients with brain metastases, those who survived 4 months or longer showed a significant reduction in neurocognitive function failure (NCFF) when treated with hippocampal avoidant whole brain radiotherapy (HA-WBRT) compared to standard WBRT.
Patients with lower baseline cognitive impairment (as measured by the MD Anderson Symptom Inventory-Brain Tumor scores) and those with primary lung tumors experienced greater neuroprotective benefits from HA-WBRT, highlighting the importance of individual patient characteristics in treatment response.
Evaluating the Heterogeneity of Hippocampal Avoidant Whole Brain Radiotherapy Treatment Effect: A Secondary Analysis of NRG CC001.Cherng, HR., Sun, K., Bentzen, S., et al.[2023]
In a study involving 38 patients with advanced non-small cell lung cancer (NSCLC), the combination of berzosertib and gemcitabine was found to be well tolerated, with common side effects including fatigue (55.3%) and anemia (52.6%).
The objective response rate (ORR) was 10.5% overall, but higher response rates were observed in patients with specific genomic features: 30.0% in those with high loss of heterozygosity and 33.0% in those with high tumor mutational burden, suggesting that genomic selection may enhance treatment efficacy.
A phase 1b study evaluating the safety and preliminary efficacy of berzosertib in combination with gemcitabine in patients with advanced non-small cell lung cancer.Plummer, R., Dean, E., Arkenau, HT., et al.[2022]

Citations

Study Details | Testing the Safety of M6620 (VX-970) When ...An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...
ATR inhibitor M6620 (VX-970) enhances the effect of radiation ...M6620 enhances the effect of radiation in our preclinical NSCLC brain metastasis models, supporting the ongoing clinical trial (NCT02589522) evaluating M6620 in ...
ATR Inhibitor M6620 (VX-970) Enhances the Effect of ...M6620 enhances the effect of radiation in our preclinical NSCLC brain metastasis models, supporting the ongoing clinical trial (NCT02589522) evaluating M6620 ...
Berzosertib + Radiation for Brain Metastases from Lung ...Giving berzosertib together with radiation therapy may work better compared to standard of care treatment, including brain surgery and radiation therapy, in ...
Phase I Study of ATR Inhibitor M6620 in Combination With ...This report is the first of an ATR inhibitor-chemotherapy combination. The maximum dose of topotecan plus M6620 is tolerable.
Testing the Safety of M6620 (VX-970) When Given With ...The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure.
Clinical TrialsThe purpose of this study is to assess the side effects and best dose of ATR kinase inhibitor VX-970 when given together with whole brain radiation therapy for ...
Phase 1 study of the ATR inhibitor berzosertib in ...Berzosertib plus cisplatin is well tolerated and shows preliminary clinical activity in patients with advanced solid tumours, warranting further evaluation in ...
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