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Metastatic Breast CancerPhase 1/2NCT00825734

Phase I/II Trial of Sorafenib Plus Ixabepilone in HER2-Negative Metastatic Breast Cancer

A Phase 1/2 study testing Sorafenib and Ixabepilone in people with Metastatic Breast Cancer, run by SCRI Development Innovations, LLC at 15 sites in United States.

Completed

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

Official record
Search all trials

Trial summary

In this study, patients with metastatic HER2-negative breast cancer will receive treatment with ixabepilone and sorafenib until disease progression or unacceptable toxicity occurs. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Breast Cancer
What is being tested?
Sorafenib and Ixabepilone
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
83 participants
Where
15 sitesUnited States
Study dates
Mar 2009to Aug 2014
Phase
Phase 1/2
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

  • Age ≥ 18 years.
  • Histologically or cytologically confirmed breast cancer diagnosis
  • with metastatic disease. Patients without pathologic or cytologic
  • confirmation of metastatic disease should have unequivocal
  • evidence of metastasis.
  • 3. Measurable disease, as per RECIST criteria (Therasse et al.
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  • 2000). Measurable disease cannot be previously irradiated
  • unless progression was documented. Measurable disease is
  • defined as: at least one lesion that can be accurately measured in
  • at least one dimension [longest diameter to be recorded] as
  • >20 mm with conventional techniques, or as >10 mm with spiral
  • computed tomography (CT) scan. Disease must be measurable,
  • i.e., bone-only disease or evaluable-only disease is not eligible.
  • 4. Patients with brain metastasis may participate if they:
  • have undergone appropriate treatment,
  • are at least 1 month post-treatment,
  • have no neurologic symptoms,
  • are not on steroids,
  • have a follow-up magnetic resonance imaging (MRI) scan that
  • demonstrates no residual active lesions, and
  • have no new untreated lesions.
  • 5 The following prior therapies are allowed:
  • No prior chemotherapy in the metastatic setting. However,
  • patients must have received prior adjuvant or neo-adjuvant
  • chemotherapy.
  • Prior radiation therapy in either the metastatic or early-stage
  • setting, as long as <25% of the bone marrow has been
  • treated. Radiation therapy must be completed at least
  • 14 days prior to study registration, and all radiation-related
  • toxicities must be resolved to ≤ grade 1 before the patient is
  • eligible for study inclusion.
  • Any number of hormonal therapies in the neo-adjuvant,
  • adjuvant, or metastatic setting is allowed. Patients must
  • discontinue hormonal therapy at least 1 week prior to starting
  • study treatment.
  • •Prior bevacizumab administered >4 weeks before initiation of
  • study treatment is allowed.
  • 6 HER2-negative status. Documentation of HER2 results must be
  • available at the time of study enrollment. HER2-negative is
  • defined as:
  • Immunohistochemical (IHC) 0 or IHC 1+ OR
  • Fluorescence in situ hybridization (FISH) negative (defined by
  • FISH ratio <2.2) OR
  • Silver in-situ hybridization (SISH) negative (defined by SISH
  • ratio <2.2).
  • Patients with an IHC 2+ will need to be validated as HER2-negative
  • by FISH.
  • 7 An Eastern Cooperative Oncology Group (ECOG) performance
  • status of < or = to 2.
  • 8. Normal bone marrow function as defined by:
  • absolute neutrophil count (ANC) >1,500/μL;
  • platelets >100,000/μL;
  • hemoglobin >9 g/dL.
  • 9 Normal hepatic function as defined by:
  • total bilirubin within normal institutional limits;
  • aspartate aminotransferase (AST) and alanine
  • aminotransferase (ALT) <2.5 × the institutional upper limit of
  • normal (ULN) for patients without liver metastasis; <5.0 × ULN
  • for patients with liver metastasis.
  • 10. Normal renal function as defined by creatinine <1.5 × ULN.
  • 11. Left ventricular ejection fraction (LVEF) within institutional limits of
  • normal.
  • 12. International normalized ratio (INR) <1.5 or a prothrombin
  • time/partial thromboplastin time (PT/PTT) within normal limits.
  • Patients receiving anti-coagulation treatment with an agent such
  • as warfarin or heparin may be allowed to participate. The INR
  • should be measured prior to initiation of sorafenib, and for
  • patients on warfarin, INR should be monitored at least weekly
  • following initiation of protocol treatment, until the INR is stable and
  • therapeutic.
  • 13. Life expectancy of >6 months.
  • 14. For women of childbearing potential, negative serum pregnancy
  • test within 7 days prior to starting treatment.
  • 15. For women of childbearing potential and men, agreement to use a
  • method of contraception that is acceptable to their physician from
  • time of first signing the informed consent and for the study
  • duration. Men should use adequate birth control for at least three
  • months after the last administration of sorafenib. If a woman
  • becomes pregnant or suspects she is pregnant while participating
  • in this study, she must agree to inform her treating physician
  • immediately. As applicable, patients must agree to discontinue
  • breast-feeding until at least 3 weeks after their last dose of study
  • drug.
  • 16. Recovery to < grade 1 toxicity due to prior therapy.
  • 17. Ability to understand and willingness to sign a written informed
  • consent document.

Who cannot join

  • More than one (>1) prior chemotherapy regimen.
  • Treatment with chemotherapy, biologic agents, or targeted agents
  • within the previous 4 weeks.
  • Previous treatment with sorafenib or ixabepilone.
  • Women who are pregnant or breastfeeding.
  • Neuropathy (motor or sensory) greater than grade 1.
Show all 57Show fewer
  • Uncontrolled intercurrent illness including (but not limited to)
  • ongoing or active infection >grade 2.
  • Known history of human immunodeficiency virus (HIV), Hepatitis
  • B, or Hepatitis C infection.
  • History of other non-breast cancer malignancy treated with
  • curative intent within the 5 years preceding study enrollment with
  • the exception of carcinoma in situ of the cervix, non-melanoma
  • skin cancer, or follicular thyroid cancer.
  • Concurrent hormonal therapy, chemotherapy other than
  • ixabepilone, or radiation treatments while on study as well as
  • treatment with other investigational agents while on study.
  • Cardiac disease:
  • •Congestive heart failure (CHF) greater than New York Heart Association
  • (NYHA) Class II (see Appendix B).
  • Unstable angina (anginal symptoms at rest) or new onset angina
  • (i.e., began within the last 3 months).
  • Myocardial infarction within the past 6 months.
  • Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
  • Uncontrolled hypertension (systolic blood pressure >150 mmHg
  • or diastolic pressure >100 mmHg despite optimal medical
  • management).
  • Thrombolic or embolic events such as cerebrovascular accident,
  • including transient ischemic attacks, within the past 6 months.
  • Pulmonary hemorrhage or bleeding event ≥ grade 2 within
  • 4 weeks of the first dose of study treatment, or any other
  • hemorrhage or bleeding event ≥ grade 3 within 4 weeks of the
  • first dose of study treatment.
  • 14. Serious non-healing wound, ulcer, or bone fracture.
  • 15. Evidence or history of bleeding diathesis or coagulopathy.
  • 16. Major surgery, open biopsy or significant traumatic injury within
  • 4 weeks of the first dose of study drugs or anticipation of the need
  • for major surgical procedure.
  • 17. Chronic use of CYP3A4 inducers and use of the following strong
  • CYP3A4 inhibitors: ketoconazole, itraconazole, clarithromycin,
  • atazanavir, nefazodone, saquinavir, telithromycin, ritonavir,
  • amprenavir, indinavir, nelfinavir, delavirdine, and voriconazole.
  • Use of these agents should be discontinued at least 72 hours
  • prior to initiation of study treatment.
  • 18. Use of St. John's Wort or rifampin (rifampicin).
  • 19. Any condition that impairs patient's ability to swallow whole pills or
  • gastrointestinal (GI) tract disease that involves an inability to take
  • oral medication, malabsorption syndrome, a requirement for
  • intravenous (IV) alimentation, prior surgical procedures affecting
  • absorption, or uncontrolled inflammatory GI disease (e.g., Crohn's
  • disease or ulcerative colitis).
  • 20. Psychiatric illness/social situations that would limit compliance
  • with study requirements.
  • 21. Known or suspected allergy to sorafenib, Cremophor EL
  • (polyoxyethylated castor oil) or a drug formulated in
  • Cremophor EL such as paclitaxel or any other agent given in the
  • course of this trial.

Trial locations and contacts

15 sites in 1 country.

15 sites in 1 country

United States15 sites

  • Hematology Oncology Clinic, LLP

    Baton Rouge, Louisiana, 70806

  • Center for Cancer and Blood Disorders

    Bethesda, Maryland, 20817

  • National Capital Clinical Research Consortium

    Bethesda, Maryland, 20817

  • St. Louis Cancer Care

    Chesterfield, Missouri, 63044

  • Oncology Hematology Care

    Cincinnati, Ohio, 45242

  • South Carolina Oncology Associates

    Columbia, South Carolina, 29210

  • Florida Cancer Specialists

    Fort Myers, Florida, 33916

  • Baptist Hospital East

    Louisville, Kentucky, 40207

  • Hematology-Oncology Associates of Northern NJ

    Morristown, New Jersey, 07962

  • Tennessee Oncology, PLLC

    Nashville, Tennessee, 37023

  • Mercy Hospital

    Portland, Maine, 04101

  • Portsmouth Regional Hospital

    Portsmouth, New Hampshire, 03801

  • Spartanburg Regional Medical Center

    Spartanburg, South Carolina

  • Providence Medical Group

    Terre Haute, Indiana, 47802

  • RHHP/ Hope Cancer Center

    Terre Haute, Indiana, 47802

Other trials in United States

About this study

Official title: Phase I/II Trial of Sorafenib Plus Ixabepilone in HER2-Negative Metastatic Breast Cancer (MBC)

In this study, patients with metastatic HER2-negative breast cancer will receive treatment with ixabepilone and sorafenib until disease progression or unacceptable toxicity occurs. The Phase I portion of this study will determine the maximum tolerated doses (MTDs) of sorafenib and ixabepilone that may be used in combination for first- or second-line treatment of MBC. The MTDs identified in the Phase I portion of the study will be used in the Phase II portion which will evaluate the efficacy and safety of the combination of sorafenib and ixabepilone in patients who have received at least one prior chemotherapy treatment in either the adjuvant or neoadjuvant setting or following one prior MBC chemotherapy in MBC patients who had not received prior adjuvant or neoadjuvant breast cancer chemotherapy. This will be one of the initial trials investigating the use of this treatment combination for MBC.

This trial will be conducted under the leadership of the Sarah Cannon Research Institute (SCRI) Oncology Research Consortium, a community-based, multi-center, clinical trial organization.

Being tested
Sorafenib, Ixabepilone
Keywords
Metastatic Breast Cancer, Sorafenib, Nexavar, Ixabepilone, Ixempra
Medical subject headings
Breast Neoplasms

What participants receive

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

  • SorafenibDrug

    Also called Nexavar (Sorafenib)

    Dose Level 1 - Sorafenib PO BID (200mg) Dose Level -1 - Sorafenib PO BID (200mg) Dose Level 1a - Sorafenib PO BID (400mg)

  • IxabepiloneDrug

    Also called Ixempra (Ixabepilone)

    Dose Level 1 - Ixabepilone IV every 21 days (40mg/m^2) Dose Level -1 - Ixabepilone IV every 21 days (32mg/m^2) Dose Level 1a - Ixabepilone IV every 21 days (32mg/m^2)

Study groups in NCT00825734
Study groupRoleWhat they receive
Dose Level 1ExperimentalSorafenib PO BID (200mg), Ixabepilone IV every 21 days (40mg/m^2)
Receives: Drug: Sorafenib; Drug: Ixabepilone
Dose Level -1ExperimentalSorafenib PO BID (200mg), Ixabepilone IV every 21 days (32mg/m^2)
Receives: Drug: Sorafenib; Drug: Ixabepilone
Dose Level 1aExperimentalSorafenib PO BID (400mg), Ixabepilone IV every 21 days (32mg/m^2)
Receives: Drug: Sorafenib; Drug: Ixabepilone

What is being measured

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

  1. Progression-Free Survival (PFS)

    Measured from Day 1 of study drug administration to disease progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) - progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

    Measured: every 9 weeks until treatment discontinuation or death on study

Secondary outcomes (4)

  1. 6-month Progression-Free Survival

    Measured from Day 1 of study drug administration to disease progression as defined by RECIST v1.1, or death on study. Progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

    Measured: every 9 weeks, up to 6 months

  2. Objective Response Rate

    Objective Response will be evaluated in this study using the Response Evaluation Criteria in Solid Tumors (RECIST).

    Measured: every 9 weeks until discontinuation of treatment

  3. Overall Survival (OS)

    Measured from Day 1 of study drug administration to date of death due to any cause.

    Measured: every 9 weeks until treatment discontinuation or death on study

  4. Number of Patients With Adverse Events as a Measure of of Safety and Tolerability

    Assessments are made through analysis of reported incidence of treatment-emergent AEs and SAEs.

    Measured: every 9 weeks until treatment discontinuation or unacceptable toxicity

Timeline

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

  1. First posted21 Jan 2009 (estimated)
  2. Study startMar 2009
  3. Primary completionJun 2013
  4. Study completionAug 2014

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
83 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00825734
Sponsor's protocol ID
SCRI BRE 138
Status last verified
Dec 2014
First submitted
19 Jan 2009
Last updated
22 Dec 2014
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Sorafenib and Ixabepilone in people with Metastatic Breast Cancer, run by SCRI Development Innovations, LLC at 15 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 86 inclusion and 57 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 22 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 22 Dec 2014). 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?

Progression-Free Survival (PFS) (time frame: every 9 weeks until treatment discontinuation or death on study). 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 NCT00825734.

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 22 Dec 2014.

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