15 Participants Needed
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Berzosertib + Radiation for Brain Metastases from Lung Cancer

Recruiting at 8 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)

Trial Summary

What is the purpose of this trial?

This phase I trial studies the side effects and best dose of berzosertib (M6620 \[VX-970\]) when given together with whole brain radiation therapy in treating patients with non-small cell lung cancer, small cell lung cancer, or neuroendocrine tumors that have spread from the original (primary) tumor to the brain (brain metastases). Berzosertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving berzosertib together with radiation therapy may work better compared to standard of care treatment, including brain surgery and radiation therapy, in treating patients with non-small cell lung cancer, small cell lung cancer, or neuroendocrine tumors.

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.

What data supports the effectiveness of the treatment Berzosertib + Radiation for Brain Metastases from Lung Cancer?

Research shows that combining whole-brain radiotherapy (WBRT) with other drugs like erlotinib and gefitinib can improve response rates in treating brain metastases from lung cancer. Additionally, berzosertib has shown preliminary effectiveness when combined with other treatments in advanced lung cancer, suggesting potential benefits when used with WBRT.12345

Is the combination of Berzosertib and whole-brain radiotherapy safe for treating brain metastases from lung cancer?

The safety of whole-brain radiotherapy (WBRT) has been evaluated in various studies, showing it can be associated with a decline in neurocognitive function (thinking and memory skills). Hippocampal avoidant WBRT (HA-WBRT) is a newer method designed to reduce this risk, but specific safety data for Berzosertib combined with WBRT is not available in the provided research.23467

How is the treatment with Berzosertib and radiation different for brain metastases from lung cancer?

The treatment with Berzosertib and radiation is unique because it combines a novel drug, Berzosertib, which targets DNA repair mechanisms in cancer cells, with whole-brain radiotherapy (WBRT), potentially enhancing the effectiveness of radiation by making cancer cells more sensitive to it. This approach differs from other treatments that typically combine WBRT with drugs like gefitinib or erlotinib, which target specific growth signals in cancer cells.24689

Research Team

PM

Pranshu Mohindra

Principal Investigator

Mayo Clinic Cancer Center LAO

Eligibility Criteria

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.
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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

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

Treatment Details

Interventions

  • Berzosertib (M6620 [VX-970])
  • Whole-Brain Radiotherapy
Trial OverviewThe 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.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Group II (VX-970, surgery, whole-brain radiation therapy)Experimental Treatment4 Interventions
Patients receive berzosertib IV over 60-90 minutes 2-4 hours prior to surgery. After surgery, patients undergo whole-brain radiation therapy and receive berzosertib as in Group I.
Group II: Group I (VX-970, whole-brain radiation therapy)Experimental Treatment3 Interventions
Patients undergo whole-brain radiation therapy QD 5 days a week for 15 fractions. Patients also receive berzosertib IV over 60-90 minutes twice a week, 18-30 hours after first radiation therapy. Treatment continues for 3 weeks in the absence of disease progression or unacceptable toxicity.

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials
14,080
Recruited
41,180,000+

Findings from Research

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]
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]

References

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. [2022]
Combining Whole-Brain Radiotherapy with Gefitinib/Erlotinib for Brain Metastases from Non-Small-Cell Lung Cancer: A Meta-Analysis. [2022]
Whole-brain irradiation with hippocampal sparing and dose escalation on metastases: neurocognitive testing and biological imaging (HIPPORAD) - a phase II prospective randomized multicenter trial (NOA-14, ARO 2015-3, DKTK-ROG). [2021]
Whole-brain radiotherapy with and without concurrent erlotinib in NSCLC with brain metastases: a multicenter, open-label, randomized, controlled phase III trial. [2021]
Bevacizumab and gefitinib enhanced whole-brain radiation therapy for brain metastases due to non-small-cell lung cancer. [2018]
Results of hypofractionated whole brain radiotherapy (2×8 Gy) for patients with brain metastases from lung cancer. [2018]
Evaluating the Heterogeneity of Hippocampal Avoidant Whole Brain Radiotherapy Treatment Effect: A Secondary Analysis of NRG CC001. [2023]
Role of radiotherapy in the management of brain metastases of NSCLC - Decision criteria in clinical routine. [2021]
[Radiotherapy concomitant with first-generation epidermal growth factor receptor tyrosine kinase inhibitors in the treatment of brain metastases from non small cell lung cancer: a meta-analysis]. [2018]