NCT02589522

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

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

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 15 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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 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: I. 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: I. 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: I. 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
• Stage IVB Lung Cancer AJCC v8

Interventions

Type	Name	Description
DRUG	Berzosertib	Given IV
OTHER	Quality-of-Life Assessment	Ancillary studies
PROCEDURE	Therapeutic Conventional Surgery	Undergo surgery
RADIATION	Whole-Brain Radiotherapy	Undergo whole-brain radiation therapy

Timeline

• Start date: 2017-05-22
• Primary completion: 2021-08-23
• Completion: 2026-09-18
• First posted: 2015-10-28
• Last updated: 2025-10-08
• Results posted: 2023-05-19

Locations

9 sites across 1 country: United States

Regulatory

• FDA-regulated drug study