Clinical trial NCT00622466: Sorafenib and Paclitaxel in Treating Patients With Metastatic Breast Cancer
Official title: Phase II Trial of Sorafenib and Paclitaxel for Measurable Metastatic HER2-Negative Breast Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: stage IV breast cancer
male breast cancer
recurrent breast cancer
HER2-negative breast cancer
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
First posted: 2008-02-25
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving sorafenib together with paclitaxel may kill more tumor cells.

PURPOSE: This phase II trial is studying the side effects of giving sorafenib together with paclitaxel and to how well it works in treating patients with metastatic breast cancer.

Detailed description: OBJECTIVES:

Primary

* To evaluate the efficacy of sorafenib tosylate and paclitaxel by measuring tumor response, as defined by RECIST criteria, in patients with metastatic, HER2-negative breast cancer.

Secondary

* To evaluate time to disease progression in patients treated with this regimen.
* To evaluate six-month progression-free survival of patients treated with this regimen.
* To evaluate time to treatment failure in patients treated with this regimen.
* To evaluate clinical benefit rate (tumor response and stable disease) at 24 weeks in patients treated with this regimen.
* To evaluate duration of response in patients treated with this regimen.
* To evaluate the tolerability of this regimen in these patients.
* To examine the relationship of gene expression and tissue/serum protein markers, where available, related to response to therapy focusing on growth factor receptor pathways.

OUTLINE: This is a multicenter study.

Patients receive oral sorafenib tosylate twice daily on days 1-28 and paclitaxel IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 4 weeks.

Eligibility criteria: DISEASE CHARACTERISTICS:

Inclusion criteria:

* Histologically\* confirmed breast cancer

  * Stage IV (metastatic) disease

    * Radiographic evidence of metastases NOTE: \*Histological confirmation of the actual metastasis is not required.
* Measurable disease by RECIST criteria defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques (i.e., physical examination, CT scan, MRI, or x-ray) or ≥ 10 mm by spiral CT scan

  * No prior radiotherapy unless growth has been documented following radiotherapy
* Primary tumor or metastatic tumor HER2-negative, defined as the following:

  * Immunohistochemistry of 0 or 1+ OR the equivalent, if an automated quantitative assay is used
  * HER2 fluorescent in situ hybridization (FISH) assay negative as defined by a HER2:chromosome 17 centromeric probe ratio \< 1.8 (or \< 2.2 if immunohistochemistry is less than 3+ or equivalent) OR equivalent values for negative FISH assays that do not normalize to chromosome 17
* Hormone-receptor positive (estrogen receptor-\[ER\] or progesterone receptor \[PgR\]-positive) disease or hormone receptor-negative (ER- or PgR-negative) disease
* Tumor block from initial breast cancer primary or a biopsy of a metastatic site must be available for correlative studies
* Brain metastases allowed provided the patient is stable after completion of treatment (i.e., surgery and/or radiotherapy), asymptomatic, and off steroids with 2 consecutive stable brain scans at least 4 weeks after radiotherapy

Exclusion criteria:

* Bone-only or other nonmeasurable-only disease
* Newly diagnosed brain metastases

PATIENT CHARACTERISTICS:

Inclusion criteria:

* ECOG performance status 0-1
* Life expectancy \> 6 months
* Menopausal status not specified
* WBC ≥ 3,000/mcL
* Absolute neutrophil count ≥ 1,500/mcL
* Platelets ≥ 100,000/mcL
* Total bilirubin \< 1.5 times upper limit of normal (ULN)
* AST and ALT transaminases ≤ 2.5 times ULN (\< 5 times ULN if liver involvement)
* Creatinine \< 1.5 times ULN OR creatinine clearance \> 60 mL/min
* INR \< 1.5 OR PT/PTT normal
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception prior to and during (women and men) and for at least 3 months after (men) study therapy
* Able to swallow and absorb oral medications

Exclusion criteria:

* Active or uncontrolled medical illness (e.g., active infection \> CTCAE grade 2), including any of the following:

  * HIV or chronic hepatitis B or C
  * Uncontrolled diabetes
  * NYHA class II-IV uncompensated congestive heart failure
  * Unstable angina (anginal symptoms at rest)
  * New onset angina (i.e., began within the past 3 months)
  * Coronary artery disease
* Myocardial infarction within the past 6 months
* Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
* Evidence of bleeding diathesis or coagulopathy
* Pulmonary hemorrhage/bleeding event \> CTCAE grade 2 within 4 weeks of first dose of study drug
* Any other hemorrhage/bleeding event \> CTCAE grade 3 within 4 weeks of first study drug
* Thrombotic or embolic events (i.e., cerebrovascular accident), including transient ischemic attacks within the past 6 months
* Hypertension that cannot be controlled with medication to ≤ 150/90 mm Hg
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to sorafenib tosylate
* Prior invasive cancer other than breast cancer except nonmelanoma skin cancer
* Chronic nonhealing wound or ulcer

PRIOR CONCURRENT THERAPY:

* No more than 1 prior chemotherapy regimen for metastatic breast cancer (MBC)
* At least 3 weeks since prior hormonal therapy for MBC or adjuvant or neoadjuvant chemotherapy

  * More than 1 year since adjuvant paclitaxel
* At least 4 weeks since major thoracic, abdominal, or pelvic surgery and recovered
* At least 3 weeks since prior and no concurrent investigational drugs
* Concurrent bisphosphonates allowed
* Concurrent anticoagulation agents (i.e., warfarin or heparin) allowed
* No anticipated need for or concurrent radiotherapy
* No concurrent Hypericum perforatum (St. John wort) or rifampin (rifampicin)
* No other concurrent anti-neoplastic drugs

Primary outcomes:
measure: Time to Tumor Progression
timeFrame: Time from first treatment to disease progression or death (up to 36 months)
Secondary outcomes:
measure: Tumor Response Rate
timeFrame: Up to 36 months
measure: Six-month Progression-free Survival
timeFrame: 6 months
measure: Time to Treatment Failure
timeFrame: Up to 36 months
measure: Clinical Benefit Rate (Tumor Response and Stable Disease) at 24 Weeks
timeFrame: 24 weeks
measure: Duration of Response
timeFrame: Up to 36 months
measure: Tolerability of Sorafenib/Paclitaxel Regimen
timeFrame: Up to 36 months
measure: Determine the Relationship of Gene Expression and Tissue/Serum Protein Markers, Where Available, Related to Response to Therapy Focusing on Growth Factor Receptor Pathways.
timeFrame: Up to 36 months
Other outcomes:
Locations:
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
Study officials:
affiliation: Simmons Cancer Center
name: Barbara B. Haley, MD
role: PRINCIPAL_INVESTIGATOR
References: