Metastatic Lung Neuroendocrine NeoplasmPhase 1NCT02589522
Testing the Safety of M6620 (VX-970) When Given With Standard Whole Brain Radiation Therapy for the Treatment of Brain Metastases From Non-small Cell Lung Cancer, Small Cell Lung Cancer, or Neuroendocrine Tumors
A Phase 1 study testing Berzosertib, Quality-of-Life Assessment and Therapeutic Conventional Surgery in people with Metastatic Lung Neuroendocrine Neoplasm and Metastatic Lung Non-Small Cell Carcinoma, run by National Cancer Institute (NCI) at 9 sites in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Lung Neuroendocrine Neoplasm, Metastatic Lung Non-Small Cell Carcinoma, Metastatic Lung Small Cell Carcinoma
- What is being tested?
- Berzosertib, Quality-of-Life Assessment and Therapeutic Conventional Surgery
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 9 sitesUnited States
- Study dates
- 22 May 2017to 17 Sep 2027
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with a histologically confirmed diagnosis of non-small cell lung cancer (NSCLC), including neuroendocrine tumors or small cell lung cancer (SCLC) who are being evaluated for palliative WBRT (with or without neurosurgical resection or stereotactic radiosurgery [SRS]) for radiologically or histologically diagnosed brain metastases presumed to be from the lung cancer are eligible for this Phase I study. Group 2 will only include NSCLC patients.
- Life expectance of greater than two months to allow completion of study treatment and assessment of dose-limiting toxicity
- Group 2 patients should have archived or fresh tumor tissue available from the non-craniotomy site and will have fresh tumor tissue available from the planned craniotomy
- Age >= 18 years. Because no dosing or adverse event data are currently available on the use of M6620 (VX-970, berzosertib) in patients < 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
- Note: though patients with ECOG performance status of 3 due to neurological deficits who are otherwise fit to receive systemic therapy per clinician assessments will be allowed
Show all 15Show fewer
- Leukocytes >= 3,000/mcL
- Absolute neutrophil count (ANC) >= 1,500/mcL
- Platelets >= 100,000/mcL
- If no known liver metastases: total bilirubin < 1.5 x institutional upper limit of normal (ULN); if known liver metastases, then: total bilirubin < 2.5 x ULN
- If no known liver metastases: aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) or alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) < 2 x ULN; if known liver metastases, then: AST/SGOT of ALT/SGPT < 5 x ULN
- Creatinine within normal institutional limits for age OR creatinine clearance >= 45 mL/min/1.73 m^2 for patients with creatinine levels above ULN
- Negative serum or urine pregnancy test result for females of child bearing potential
- The effects of M6620 (VX-970, berzosertib) on the developing human fetus are unknown. For this reason and because radiation therapy is known to have teratogenic potential, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of M6620 (VX-970, berzosertib) administration.
- Ability to understand and the willingness to sign a written informed consent document
Who cannot join
- Patients with 1-3 brain metastases, each < 3 cm by contrast MRI, with stable systemic disease and ECOG score of 0-2, who would otherwise be eligible for SRS/stereotactic radiation therapy (SRT) alone should not be enrolled into this study unless WBRT is recommended due to any medical reasons or logistic limitations as determined by the treating physician. Patients who develop recurrence post-SRS/SRT or surgery alone and are recommended WBRT will be eligible for the protocol.
- Greater than 1 cm mid-line shift, severe uncal herniation or significant hemorrhage/hydrocephalus (intra-lesional hemorrhage is acceptable). Patients with seizure at presentation who have been started on levetiracetam and have been stable for 48 hours prior to study registration are eligible at the discretion of treating physician
- Patients who have received systemic cytotoxic chemotherapy and/or, immunotherapy or other intravenous standard therapy for 2 weeks before initiation of planned WBRT, for oral targeted agents 3-7 days per clinician discretion or patients who have not recovered to Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or less from serious (CTCAE grade 3 or more) adverse events form the previously received agents. For any other investigational agents, at least 4 half-lives of the agent (6 weeks for nitrosoureas or mitomycin C) should have elapsed prior to starting study treatment
- Patients must not have received prior WBRT (previous SRS/SRT done at least 2 weeks from the planned start of WBRT is acceptable). Patients planned upfront to undergo SRS/SRT/fractionated boosts or neurosurgery after WBRT are not eligible; however, these treatments/procedures can be performed once the dose limiting toxicity (DLT) assessment has been completed, if felt clinically necessary
- Pregnant women are excluded from this study because M6620 (VX-970, berzosertib) as a deoxyribonucleic acid (DNA)-damage response (DDR) inhibitor may have the potential for teratogenic or abortifacient effects. Further, radiation therapy is known to have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with M6620 (VX-970, berzosertib), breastfeeding should be discontinued if the mother is treated with M6620 (VX-970, berzosertib).
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to M6620 (VX-970, berzosertib).
Show all 11Show fewer
- M6620 (VX-970, berzosertib) is primarily metabolized by cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4); therefore, concomitant administration with strong inhibitors or inducers of CYP3A4 should be avoided. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference for a list of drugs to avoid or minimize use of. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product. Ongoing phenytoin should be either discontinued if clinically safe or transitioned to non-enzyme-inducing antiepileptics like levetiracetam with a 8-day washout period (half-life 18-22 hours, time to steady-state 4-8 days) prior to first dose of M6620 (VX-970, berzosertib) (7-days prior to WBRT).
- Patients needing more than 8 mg dexamethasone per day at the time of start of WBRT will not be eligible to participate in the study. However, patients will be allowed entry into the study if it is medically safe to reduce the daily dose of dexamethasone to 8 mg or less from the day of the start of WBRT. The dexamethasone dose for such patients may be increased beyond 8 mg per day during the course of treatment if medically necessary. This increased need for dose should be communicated to the study's principal investigator, Dr Mohindra at the University of Maryland.
- Uncontrolled intercurrent illness that would increase the risk of toxicity or limit compliance with study requirements. This includes but is not limited to, ongoing uncontrolled serious infection requiring i.v. antibiotics at the time of registration, or psychiatric illness/social situations that would limit compliance with study requirements
- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with M6620 (VX-970, berzosertib) and the uncertainties of any impact thereof on the radiation toxicities. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
- Patients with known diagnoses that are associated with germline DDR defects such as Li Fraumeni syndrome and ataxia telangiectasia are excluded from the study as M6620 (VX-970, berzosertib) is a DDR inhibitor.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, 21201
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
Case Western Reserve University
Cleveland, Ohio, 44106
City of Hope Comprehensive Cancer Center
Duarte, California, 91010
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: Phase 1 Trial to Determine the Recommended Phase 2 Dose (RP2D) of M6620 (VX-970, Berzosertib) When Combined With Whole Brain Radiotherapy (WBRT) in Patients With Brain Metastases From Lung Cancer
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.
Read the detailed description
PRIMARY OBJECTIVE:
- To conduct a phase 1 dose escalation trial in patients with brain metastases from non-small cell lung cancer (NSCLC) to determine the recommended phase 2 dose (RP2D) of twice weekly intravenous (i.v.) M6620 (VX-970, berzosertib) administered concurrent with conventionally fractionated whole brain radiotherapy (WBRT), with M6620 (VX-970, berzosertib) starting 18-30 hours after the first dose of radiation (but prior to the second fraction of radiation).
SECONDARY OBJECTIVES:
- To estimate the incidence of >= grade 3 delayed neurological toxicity at 2, 4 and 6-months post-completion of whole-brain radiotherapy (for patients without intracranial progression).
II. To observe and record anti-tumor activity. IIa. To estimate the radiological response rates (RR) at 6 months including bi-directional and volumetric measurements of lesion size.
IIb. To estimate the intracranial 6-month progression-free survival (PFS).
EXPLORATORY/HYPOTHESIS GENERATING OBJECTIVES:
- Changes in dynamic susceptibility contrast enhancement (DSC-magnetic resonance imaging [MRI]) perfusion and mean apparent diffusion coefficient (ADC) measurements in diffusion-weighted magnetic resonance imaging (DWI). (Group I) II. To measure cerebrospinal fluid (CSF) M6620 (VX-970, berzosertib) levels, tumor M6620 (VX-970, berzosertib) levels, and pATR T1989, pCHK1 S345 and RAD51 multiplex foci. (Group II) III. Changes in DSC-MRI perfusion and mean ADC measurements in DWI. (Group II)
OUTLINE: This is a dose-escalation study of berzosertib. Patients are assigned to 1 of 2 treatment groups.
GROUP I: Patients undergo whole-brain radiation therapy once daily (QD), 5 days a week for 15 fractions. Patients also receive berzosertib intravenously (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.
GROUP II: 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.
After completion of study treatment, patients are followed up every 2 months for 6 months, every 3-4 months for 6 months, then every 6 months for 1 year.
- Conditions
- Metastatic Lung Neuroendocrine Neoplasm, Metastatic Lung Non-Small Cell Carcinoma, Metastatic Lung Small Cell Carcinoma, Metastatic Malignant Neoplasm in the Brain, Stage IV Lung Cancer AJCC v8, Stage IVA Lung Cancer AJCC v8
- Being tested
- Berzosertib, Quality-of-Life Assessment, Therapeutic Conventional Surgery, Whole-Brain Radiotherapy
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Small Cell Lung Carcinoma, Brain Neoplasms, Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BerzosertibDrug
Also called 2-Pyrazinamine, 3-(3-(4-((Methylamino)methyl)phenyl)-5-isoxazolyl)-5-(4-((1-methylethyl)sulfonyl)phenyl)-, M 6620, M6620, VX 970
Given IV
Quality-of-Life AssessmentOther
Also called Quality of Life Assessment
Ancillary studies
Therapeutic Conventional SurgeryProcedure or surgery
Undergo surgery
Whole-Brain RadiotherapyRadiation
Also called WBRT, whole-brain radiation therapy
Undergo whole-brain radiation therapy
| Study group | Role | What they receive |
|---|---|---|
| Group I (VX-970, whole-brain radiation therapy) | Experimental | 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. Receives: Drug: Berzosertib; Other: Quality-of-Life Assessment; Radiation: Whole-Brain Radiotherapy |
| Group II (VX-970, surgery, whole-brain radiation therapy) | Experimental | 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. Receives: Drug: Berzosertib; Other: Quality-of-Life Assessment; Procedure: Therapeutic Conventional Surgery; Radiation: Whole-Brain Radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With a Dose-limiting Toxicity
Defined as any grade 3 or more non-hematological toxicity requiring more than 5 day interruption in therapy or any grade 4 or higher hematological toxicity that is attributable to the berzosertib (M6620 [VX-970]) and/or whole brain radiotherapy
Measured: Up to 3 weeks after completing whole brain radiotherapy (WBRT)
Secondary outcomes (5)
Incidence of Delayed Neurological Toxicity
Assessed using Hopkins Verbal Learning Test-Revised. Incidence of events will be expressed as proportions with exact 95% confidence limits.
Measured: Up to 6-months post-completion of WBRT
Changes in Quality of Life
Measured by the Functional Assessment of Cancer Therapy-Brain. Descriptive statistics of the actual change scores will also be provided. The median change score and quartiles will be reported. Where relevant the proportion of patients experiencing a clinically significant change in score will be reported with 95% confidence limits.
Measured: Baseline to up to 6 months post-completion of WBRT
Radiological Response Rate
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR) is the disappearance of all target lesions; Partial Response (PR) is >=30% decrease in the sum of the target lesions; Disease Progression (PD) is >= 20% increase in the smallest sum of the target lesions; Stable Disease (SD) is between PR and PD.
Measured: 6 months
Intracranial Progression-free Survival (icPFS)
Kaplan-Meier estimates of median icPFS will be calculated. Patients alive without intracranial progression at last follow-up will be censored at the date of the last radiologic assessment.
Measured: 6 months
Overall Survival (OS)
Kaplan-Meier estimates of OS will be calculated. For calculation of OS, patients alive at last follow-up will be censored. Exploratory Cox regression analysis with M6620 (VX-970) dose as a covariate will be performed.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2015 (estimated)
- Study start22 May 2017
- Primary completion23 Aug 2021
- Study completion17 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Metastatic Lung Neuroendocrine NeoplasmStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Pranshu Mohindra, Principal investigator, Mayo Clinic Cancer Center LAO
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02589522
- Sponsor's protocol ID
- NCI-2015-01779
- Other IDs
- NCI-2015-01779, HP-00068292, 9952, 9952, UM1CA186644, UM1CA186686, UM1CA186690, UM1CA186691
- Status last verified
- Sep 2026
- First submitted
- 27 Oct 2015
- Last updated
- 14 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Trial to Determine the Recommended Phase 2 Dose (RP2D) of M6620 (VX-970, Berzosertib) When Combined With Whole Brain Radiotherapy (WBRT) in Patients With Brain Metastases From Lung Cancer
- ClinicalTrials.gov ID
- NCT02589522
- Acronym / sponsor ID
- NCI-2015-01779
- Conditions
- Metastatic Lung Neuroendocrine Neoplasm, Metastatic Lung Non-Small Cell Carcinoma, Metastatic Lung Small Cell Carcinoma, Metastatic Malignant Neoplasm in the Brain, Stage IV Lung Cancer AJCC v8, Stage IVA Lung Cancer AJCC v8
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 15 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 22 May 2017 (actual)
- Primary completion
- 23 Aug 2021 (actual)
- Study completion
- 17 Sep 2027 (estimated)
- First posted
- 28 Oct 2015 (estimated)
- Results
- Posted 19 May 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVE:
- To conduct a phase 1 dose escalation trial in patients with brain metastases from non-small cell lung cancer (NSCLC) to determine the recommended phase 2 dose (RP2D) of twice weekly intravenous (i.v.) M6620 (VX-970, berzosertib) administered concurrent with conventionally fractionated whole brain radiotherapy (WBRT), with M6620 (VX-970, berzosertib) starting 18-30 hours after the first dose of radiation (but prior to the second fraction of radiation).
SECONDARY OBJECTIVES:
- To estimate the incidence of >= grade 3 delayed neurological toxicity at 2, 4 and 6-months post-completion of whole-brain radiotherapy (for patients without intracranial progression).
II. To observe and record anti-tumor activity. IIa. To estimate the radiological response rates (RR) at 6 months including bi-directional and volumetric measurements of lesion size.
IIb. To estimate the intracranial 6-month progression-free survival (PFS).
EXPLORATORY/HYPOTHESIS GENERATING OBJECTIVES:
- Changes in dynamic susceptibility contrast enhancement (DSC-magnetic resonance imaging [MRI]) perfusion and mean apparent diffusion coefficient (ADC) measurements in diffusion-weighted magnetic resonance imaging (DWI). (Group I) II. To measure cerebrospinal fluid (CSF) M6620 (VX-970, berzosertib) levels, tumor M6620 (VX-970, berzosertib) levels, and pATR T1989, pCHK1 S345 and RAD51 multiplex foci. (Group II) III. Changes in DSC-MRI perfusion and mean ADC measurements in DWI. (Group II)
OUTLINE: This is a dose-escalation study of berzosertib. Patients are assigned to 1 of 2 treatment groups.
GROUP I: Patients undergo whole-brain radiation therapy once daily (QD), 5 days a week for 15 fractions. Patients also receive berzosertib intravenously (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.
GROUP II: 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.
After completion of study treatment, patients are followed up every 2 months for 6 months, every 3-4 months for 6 months, then every 6 months for 1 year.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group I (VX-970, whole-brain radiation therapy) | Experimental | Drug: Berzosertib, Other: Quality-of-Life Assessment, Radiation: Whole-Brain RadiotherapyPatients 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. |
| Group II (VX-970, surgery, whole-brain radiation therapy) | Experimental | Drug: Berzosertib, Other: Quality-of-Life Assessment, Procedure: Therapeutic Conventional Surgery, Radiation: Whole-Brain RadiotherapyPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Patients with a histologically confirmed diagnosis of non-small cell lung cancer (NSCLC), including neuroendocrine tumors or small cell lung cancer (SCLC) who are being evaluated for palliative WBRT (with or without neurosurgical resection or stereotactic radiosurgery [SRS]) for radiologically or histologically diagnosed brain metastases presumed to be from the lung cancer are eligible for this Phase I study. Group 2 will only include NSCLC patients.
- Life expectance of greater than two months to allow completion of study treatment and assessment of dose-limiting toxicity
- Group 2 patients should have archived or fresh tumor tissue available from the non-craniotomy site and will have fresh tumor tissue available from the planned craniotomy
- Age >= 18 years. Because no dosing or adverse event data are currently available on the use of M6620 (VX-970, berzosertib) in patients < 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
Key exclusion criteria (11 listed)
- Patients with 1-3 brain metastases, each < 3 cm by contrast MRI, with stable systemic disease and ECOG score of 0-2, who would otherwise be eligible for SRS/stereotactic radiation therapy (SRT) alone should not be enrolled into this study unless WBRT is recommended due to any medical reasons or logistic limitations as determined by the treating physician. Patients who develop recurrence post-SRS/SRT or surgery alone and are recommended WBRT will be eligible for the protocol.
- Greater than 1 cm mid-line shift, severe uncal herniation or significant hemorrhage/hydrocephalus (intra-lesional hemorrhage is acceptable). Patients with seizure at presentation who have been started on levetiracetam and have been stable for 48 hours prior to study registration are eligible at the discretion of treating physician
- Patients who have received systemic cytotoxic chemotherapy and/or, immunotherapy or other intravenous standard therapy for 2 weeks before initiation of planned WBRT, for oral targeted agents 3-7 days per clinician discretion or patients who have not recovered to Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or less from serious (CTCAE grade 3 or more) adverse events form the previously received agents. For any other investigational agents, at least 4 half-lives of the agent (6 weeks for nitrosoureas or mitomycin C) should have elapsed prior to starting study treatment
- Patients must not have received prior WBRT (previous SRS/SRT done at least 2 weeks from the planned start of WBRT is acceptable). Patients planned upfront to undergo SRS/SRT/fractionated boosts or neurosurgery after WBRT are not eligible; however, these treatments/procedures can be performed once the dose limiting toxicity (DLT) assessment has been completed, if felt clinically necessary
- Pregnant women are excluded from this study because M6620 (VX-970, berzosertib) as a deoxyribonucleic acid (DNA)-damage response (DDR) inhibitor may have the potential for teratogenic or abortifacient effects. Further, radiation therapy is known to have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with M6620 (VX-970, berzosertib), breastfeeding should be discontinued if the mother is treated with M6620 (VX-970, berzosertib).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BerzosertibAlso: 2-Pyrazinamine, 3-(3-(4-((Methylamino)methyl)phenyl)-5-isoxazolyl)-5-(4-((1-methylethyl)sulfonyl)phenyl)-, M 6620, M6620, VX 970Given IV | Drug | Group I (VX-970, whole-brain radiation therapy), Group II (VX-970, surgery, whole-brain radiation therapy) |
| Quality-of-Life AssessmentAlso: Quality of Life AssessmentAncillary studies | Other | Group I (VX-970, whole-brain radiation therapy), Group II (VX-970, surgery, whole-brain radiation therapy) |
| Therapeutic Conventional SurgeryUndergo surgery | Procedure or surgery | Group II (VX-970, surgery, whole-brain radiation therapy) |
| Whole-Brain RadiotherapyAlso: WBRT, whole-brain radiation therapyUndergo whole-brain radiation therapy | Radiation | Group I (VX-970, whole-brain radiation therapy), Group II (VX-970, surgery, whole-brain radiation therapy) |
Primary outcome
Number of Participants With a Dose-limiting Toxicity
Time frame: Up to 3 weeks after completing whole brain radiotherapy (WBRT)
Defined as any grade 3 or more non-hematological toxicity requiring more than 5 day interruption in therapy or any grade 4 or higher hematological toxicity that is attributable to the berzosertib (M6620 [VX-970]) and/or whole brain radiotherapy
5 secondary outcomes
Incidence of Delayed Neurological Toxicity
Time frame: Up to 6-months post-completion of WBRT
Changes in Quality of Life
Time frame: Baseline to up to 6 months post-completion of WBRT
Radiological Response Rate
Time frame: 6 months
Intracranial Progression-free Survival (icPFS)
Time frame: 6 months
Overall Survival (OS)
Time frame: 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Metastatic Lung Neuroendocrine Neoplasm
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Enrolling by invitationObservational study
Harvesting Cells for Experimental Cancer Treatments
Melanoma, Gastrointestinal Cancer
RecruitingPhase 2
Testing Lutetium Lu 177 Dotatate in Patients With Somatostatin Receptor Positive Advanced Bronchial Neuroendocrine Tumors
Advanced Lung Neuroendocrine Tumor, Functioning Lung Neuroendocrine Tumor
RecruitingPhase 2
A Study of Navlimetostat (BMS-986504) Monotherapy and in Combination With Other Agents in Participants With Advanced and/or Metastatic Solid Tumors With Homozygous MTAP Deletion (MountainTAP-5)
Solid Tumors
RecruitingPhase 1
SI-B036-ST-101 in Advanced/Metastatic Solid Tumors
Locally Advanced /Metastatic Solid Tumors, Locally Advanced / Metastatic Solid Tumors
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pranshu Mohindra principal investigator
Mayo Clinic Cancer Center LAO
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Berzosertib, Quality-of-Life Assessment and Therapeutic Conventional Surgery in people with Metastatic Lung Neuroendocrine Neoplasm and Metastatic Lung Non-Small Cell Carcinoma, run by National Cancer Institute (NCI) at 9 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 14 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 May 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With a Dose-limiting Toxicity (time frame: Up to 3 weeks after completing whole brain radiotherapy (WBRT)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2026.