Whole Brain Radiotherapy (WBRT) With Sorafenib for Breast Cancer Brain Metastases (BCBM)

NCT01724606 | Completed Phase 1

• 1 other identifier: 12-046
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 6

Brief Summary

Sorafenib is a new type of anti-cancer drug. It belongs to a new class of medications known as tyrosine kinase inhibitors. Sorafenib is thought to work against cancer in many ways. It helps decrease blood supply to the tumor. It also blocks some proteins that help the tumor cells to grow." Sorafenib is approved by the Food and Drug administration (FDA) for treatment for other cancers like liver and kidney cancer. Sorafenib has also been studied in the treatment of breast cancer that has spread but is not specifically approved for the treatment of breast cancer. It has been studied both as a single agent and also in combination with other anti-cancer therapies for breast cancer. In laboratory models and in some patients with other cancers, sorafenib has been studied in tumors in the brain. In this study, sorafenib will be given together with whole brain radiation therapy (WBRT). Overall this research study is designed to answer 2 main questions:

1. 1.What dose of sorafenib should be used together with WBRT?
2. 2.What are the side effects of sorafenib and WBRT when given together?

Conditions

Breast Cancer; Brain Metastases

Keywords

Whole Brain Radiotherapy (WBRT); Sorafenib (BAY 43-9006); 12-046

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose

  Dose-escalation Phase: The proposed three dose levels of sorafenib during dose escalation are 200 mg, 400mg, and 600 mg administered daily orally. The dose-escalation phase is for 3-6 patients to be treated at each dose level. Assuming 3 dose levels during this phase, it will require a minimum of 2 and a maximum of 18 patients.

  1 year

• assessing toxicity by the number of adverse events

  using the active version of the CTCAE version 4.0

  1 year

Secondary Outcomes (1)

• CNS progression-free survival

  1 year

Study Arms (1)

Radiotherapy with Sorafenib

EXPERIMENTAL

This is a single institution, open label, prospective, phase I clinical trial using standard 3+3 design. Histologically confirmed metastatic adenocarcinoma of the breast with radiologic evidence of new and/or progressive brain metastases (BM) with a clinical indication for WBRT will be enrolled.

Radiation: Whole Brain Radiotherapy (WBRT); Drug: Sorafenib

Interventions

Whole Brain Radiotherapy (WBRT) RADIATION

WBRT (30 Gy) will be delivered in 10 fractions. Standard opposed lateral fields with multileaf collimation blocking will be used. Treatment will be administered on business days and delivered over an approximate 2 week period. Dexamethasone may be given at the discretion of the treating physician but the dose cannot exceed greater than 16mg daily as it is a strong CYP3A4 inducer. Patients will also receive a proton pump inhibitor with dexamethasone.

Radiotherapy with Sorafenib

Sorafenib DRUG

The proposed three dose levels of sorafenib during dose escalation are 200 mg, 400mg, and 600 mg administered daily orally. Patients will be enrolled in cohorts of 3.The first three subjects will take sorafenib 200 mg daily within a few hours after the first RT fraction. Sorafenib will be continued concurrently with WBRT (1 fraction /day x 10 fractions) without breaks and then continued after WBRTfor a total of 21 days. If no dose limiting toxicity (DLT) is observed in a cohort of 3 patients until two weeks after completion of WBRT, the next dose level will be evaluated.

Radiotherapy with Sorafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically-confirmed metastatic adenocarcinoma of the breast (Confirmation will be done at MSKCC)
• Age ≥18 years.
• Radiologic evidence of new and/or progressive brain metastasis (≥10 mm in longest dimension) by MR imaging of the Brain
• Life expectancy of \>12 weeks.
• Karnofsky Performance Status (KPS) of ≥70%
• If a patient is on corticosteroids, he/she must be on a non-escalating corticosteroid dose (not exceeding more than 16 mg daily of Dexamethasone oral) for ≥ 5 days.
• No limit to prior therapies with last anti-cancer treatment ≥ 2 weeks from initiation of protocol based therapy provided all toxicities (other than alopecia) have resolved to ≤Grade 1 or baseline.
• Planned WBRT based on number (≥ 3 lesions) and/or size (≥ 1 cm) of BMs (SRS) in addition to WBRT will also be eligible.
• Patients with prior SRS will also be eligible, provided that there are new, non-irradiated measurable brain lesions.
• No limit to prior therapies with last anti-cancer treatment ≥2 weeks from initiation of WBRT. Please note: there is no washout period required for trastuzumab and pertuzumab.
• Prior hormonal therapy for locally advanced or metastatic disease is allowed but this must have been discontinued prior to enrollment. No washout period will be required.
• Continuation of trastuzumab and pertuzumab are allowed for those patients already on trastuzumab and pertuzumab therapy.
• Adequate bone marrow, liver, and renal function as assessed by the following:
• Granulocyte count ≥ 1,000/μL, platelet count ≥ 100,000/μL, and hemoglobin ≥ 10 g/dL (hematologic parameters must be assessed at least 14 days after a prior transfusion, if any)
• Serum bilirubin ≤ 1.5 mg/dL; AST, ALT, and alkaline phosphatase ≤ 2.5 × ULN except for: Patients with hepatic metastases: ALT and AST ≤ 5 × ULN; patients with hepatic and/or bone metastases:

You may not qualify if:

• Leptomeningeal metastases, hemorrhagic metastases, presence of midline shift Please note: leptomeningeal metastases may be allowed if it is limited to cranial metastasis (MRI spine should be completed, within 4 weeks of enrollment, to show that no other leptomeningeal metastases is present) and is not the only metastasis present in the brain.'
• Contraindications to sorafenib
• Prior treatment with any agent that targets vascular endothelial growth factor (VEGF) or VEGF receptors (VEGFR) (licensed or investigational including sorafenib), except bevacizumab.
• Craniotomy or any other major surgery, open biopsy, or significant traumatic injury within 4 weeks of enrollment.
• Serious, non-healing wound, ulcer, or bone fracture.
• Uncontrolled seizures
• Use of cytochrome P450 enzyme-inducing anti-epileptic drugs (such as phenytoin, carbamazepine, or phenobarbital) is not allowed.
• Cardiac disease:
• Congestive heart failure \>class II New York Heart Association (NYHA) (See Appendix B, or
• Unstable angina (anginal symptoms at rest), or new-onset angina (begun within the last 3 months), or myocardial infarction within the 6 months prior to enrollment, or
• Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
• Congenital long QT syndrome or taking drugs known to prolong the QT interval ( See Appendix D or http://www. Azcert.org )
• Subjects taking any drugs with a known risk of causing torsades de pointes.
• Grade 3 hypertension ( SBP ≥ 160 mm Hg and/or DBP ≥ 100 mm Hg despite maximal medical therapy)
• ≥ Grade 2 Lipase increased (\>1.5 x ULN),

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Bayer: collaborator

Study Sites (6)

Memoral Sloan Kettering Cancer Center

Basking Ridge, New Jersey, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Cancer Center @ Suffolk

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

Location

Related Links

• Memorial Sloan-Kettering Cancer Center

MeSH Terms

Conditions

Breast Neoplasms; Brain Neoplasms

Interventions

Sorafenib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Andrew Seidman, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2012
• First Posted: November 12, 2012
• Study Start: November 5, 2012
• Primary Completion: March 1, 2022
• Study Completion: March 1, 2022
• Last Updated: March 7, 2022

Record last verified: 2022-03

Locations

US (6)