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Breast CancerPhase 1NCT01724606

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

A Phase 1 study testing Whole Brain Radiotherapy (WBRT) and Sorafenib in people with Breast Cancer and Brain Metastases, run by Memorial Sloan Kettering Cancer Center at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer, Brain Metastases
What is being tested?
Whole Brain Radiotherapy (WBRT) and Sorafenib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
6 sitesUnited States
Study dates
5 Nov 2012to 1 Mar 2022
Phase
Phase 1
Are there results?
None posted in the registry

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

  • 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.
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  • 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:
  • alkaline phosphatase ≤ 5 × ULN and patients with Gilbert's disease: serum bilirubin < 5 mg/dL
  • Serum creatinine ≤ 1.5 mg/dL or creatinine clearance of ≥ 60 mL/min based on a 24-hour urine collection
  • Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to enrollment and must agree to use adequate contraception prior to enrollment and for the duration of study participation. Subjects (men and women) of childbearing potential must agree to use adequate contraception beginning at the signing of the ICF until at least 30 days after the last dose of study drug.
  • Patients must be able to swallow and retain oral medication.

Who cannot join

  • 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
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  • 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),
  • Thrombolic, embolic, venous, or arterial events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
  • Evidence or history of bleeding diathesis or coagulopathy at the time of enrollment.
  • Pulmonary hemorrhage/bleeding event >National Cancer Institute Common Terminology for Adverse Events (NCI-CTCAE, version 4.0) Grade 2 within 4 weeks of enrollment.
  • Any other hemorrhage/bleeding event ≥NCI-CTCAE Grade 3 within 4 weeks of enrollment.
  • Therapeutic anticoagulation with Vitamin-K antagonists (e.g., warfarin) or with heparins and heparinoids. However, prophylactic anticoagulation as described below is allowed:
  • Low dose warfarin (1 mg orally, once daily) with PT-INR ≤ 1.5 x ULN is permitted. Infrequent bleeding or elevations in PT-INR have been reported in some subjects taking warfarin while on sorafenib or capecitabine therapy. Therefore, subjects taking concomitant warfarin should be monitored regularly for changes in PT, PT-INR or clinical bleeding episodes.
  • Low dose aspirin (≤ 100 mg daily).
  • Active clinically serious infection >NCI-CTCAE Grade 2.
  • Known human immunodeficiency virus (HIV) infection or chronic hepatitis B or C (the safety and effectiveness of sorafenib in this patient population have not been studied).
  • Previous or concurrent cancer that is distinct in primary site or histology from breast cancer within 5 years prior to enrollment EXCEPT cervical cancer in situ, treated basal cell carcinoma, squamous cell carcinoma (SCC), as long as it is other than SCC involving skin of the head and/or neck, and superficial bladder tumors [Ta and Tis].
  • Subjects who have used strong CYP3A4 inducers (eg, phenytoin, carbamazepine, phenobarbital, St. John's Wort [Hypericum perforatum], dexamethasone at a dose of greater than 16 mg daily for more than one day, or rifampin [rifampicin], and/or rifabutin) within 28 days before randomization.
  • Concurrent anti-cancer therapy (chemotherapy, hormonal therapy, radiation therapy (other than that specified by the protocol), surgery, immunotherapy, biologic therapy including trastuzumab, lapatinib, bevacizumab, tyrosine kinase inhibitors other than sorafenib or tumor embolization
  • Women who are pregnant or breast-feeding.
  • Use of any investigational drug within 28 days or 5 half-lives, whichever is longer, preceding enrollment. For the purposes of this study, bevacizumab will not be considered investigational therapy.
  • Inability to comply with protocol and /or not willing or not available for follow-up assessments.
  • Any condition which in the investigator's opinion makes the patient unsuitable for the study participation.

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Memoral Sloan Kettering Cancer Center

    Basking Ridge, New Jersey

  • Memorial Sloan Kettering Cancer Center @ Suffolk

    Commack, New York, 11725

  • Memorial Sloan Kettering Westchester

    Harrison, New York, 10604

  • Memorial Sloan Kettering Monmouth

    Middletown, New Jersey, 07748

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Memorial Sloan Kettering Nassau

    Uniondale, New York, 11553

Other trials in United States

About this study

Official title: Whole Brain Radiotherapy (WBRT) With Sorafenib for Breast Cancer Brain Metastases (BCBM): A Phase I Study

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. What dose of sorafenib should be used together with WBRT?
  2. What are the side effects of sorafenib and WBRT when given together?
Being tested
Whole Brain Radiotherapy (WBRT), Sorafenib
Keywords
Whole Brain Radiotherapy (WBRT), Sorafenib (BAY 43-9006), 12-046
Medical subject headings
Breast Neoplasms, Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 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.

  • SorafenibDrug

    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.

Study groups in NCT01724606
Study groupRoleWhat they receive
Radiotherapy with SorafenibExperimentalThis 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.
Receives: Radiation: Whole Brain Radiotherapy (WBRT); Drug: Sorafenib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 1 year

  2. assessing toxicity by the number of adverse events

    using the active version of the CTCAE version 4.0

    Measured: 1 year

Secondary outcomes (1)

  1. CNS progression-free survival

    CNS-PFS is defined as the interval between the date of study entry and the date of intracranial tumor progression or death from any cause. We will evaluate this during follow-up MRI scans that will be performed as a standard of care using the Macdonald criteria.

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Nov 2012 (estimated)
  2. Study start5 Nov 2012
  3. Primary completion1 Mar 2022
  4. Study completion1 Mar 2022

Resources

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01724606
Sponsor's protocol ID
12-046
Status last verified
Mar 2022
First submitted
5 Nov 2012
Last updated
7 Mar 2022
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Whole Brain Radiotherapy (WBRT) and Sorafenib in people with Breast Cancer and Brain Metastases, run by Memorial Sloan Kettering Cancer Center at 6 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 19 inclusion and 31 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: finished, as of the sponsor's last update on 7 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Maximum Tolerated Dose (time frame: 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01724606.

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 7 Mar 2022.

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