Last updated on November 2019

VX-970 and Whole Brain Radiation Therapy in Treating Patients With Brain Metastases From Non-small Cell Lung Cancer Small Cell Lung Cancer or Neuroendocrine Tumors


Brief description of study

This phase I trial studies the side effects and best dose of ATR kinase inhibitor 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. ATR kinase inhibitor M6620 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 ATR kinase inhibitor M6620 together with radiation therapy may be a better treatment for non-small cell lung cancer, small cell lung cancer, or neuroendocrine tumors.

Detailed Study Description

PRIMARY OBJECTIVES:

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.) VX-970 administered concurrent with conventionally fractionated whole brain radiotherapy (WBRT), with VX-970 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 estimate the radiological response rates (RR) at 6 months including bi-directional and volumetric measurements of lesion size.

III. To estimate the intracranial 6-month progression-free survival (PFS).

TERTIARY 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) VX-970 levels, tumor VX-970 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 ATR kinase inhibitor M6620. 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 ATR kinase inhibitor M6620 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 ATR kinase inhibitor M6620 IV over 60-90 minutes 2-4 hours prior to surgery. After surgery, patients undergo whole-brain radiation therapy and receive ATR kinase inhibitor M6620 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.

Clinical Study Identifier: NCT02589522

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