Sorafenib and Paclitaxel in Treating Patients With Metastatic Breast Cancer

Phase II Trial of Sorafenib and Paclitaxel for Measurable Metastatic HER2-Negative Breast Cancer

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00622466

Enrollment

Registered

2008-02-25

Start date

2008-04-23

Completion date

2016-10-31

Last updated

2020-10-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Breast Cancer

Keywords

stage IV breast cancer, male breast cancer, recurrent breast cancer, HER2-negative breast cancer

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.

Interventions

DRUGpaclitaxel

The chemotherapy drug called paclitaxel (Taxol) treats breast cancer, lung cancer, ovarian cancer and Kaposis sarcoma

DRUGsorafenib tosylate

Sorafenib is a type of targeted therapy known as a kinase inhibitor used to treat advanced renal cell carcinoma and unresectable hepatocellular carcinoma

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion 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

Design outcomes

Primary

Measure	Time frame	Description
Time to Tumor Progression	Time from first treatment to disease progression or death (up to 36 months)	Progression-free survival was defined as the time of treatment to the earliest date of documentation of disease progression or death due to any cause. In the case of a participant started treatment. Tenth month of progression-free rate of sorafenib and paclitaxel will be compared agains the null progression free rate of 32% using normal approximation test.

Secondary

Measure	Time frame	Description
Six-month Progression-free Survival	6 months	The proportion of patients with progression-free survival at 6 months. Progression-free is measured from Day-1 of study drug administration to disease progression as defined by Response Evaluation Criteria in Sole Tumors (RECIST) v1.1, or death on study. Progression is defined in RECIST v1.1 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 leasions.
Time to Treatment Failure	Up to 36 months	Number of patients experiencing treatment failure.
Clinical Benefit Rate (Tumor Response and Stable Disease) at 24 Weeks	24 weeks	Number of patients with either complete response (CR) or partial response (PR) as defined in Response Evaluation Criteria in Solid Tumors (for patients with measurable disease). Complete Response: Disappearance of all target lesions, disappearance of all non-target lesions for at least 4 weeks. Partial Response: At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameters.
Tumor Response Rate	Up to 36 months	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT and MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions. The confirmed response rate was estimated by the number of confirmed responses divided by the total number of participants randomized.
Tolerability of Sorafenib/Paclitaxel Regimen	Up to 36 months	Number of patients without experiencing treatment-related adverse events.
Determine the Relationship of Gene Expression and Tissue/Serum Protein Markers, Where Available, Related to Response to Therapy Focusing on Growth Factor Receptor Pathways.	Up to 36 months	Median values taken for all assays at baseline and relationship to response vs. no response will be made to identify predictive markers using methods to detect differential expression between two groups samples, including variants of the two-sample t-test, analysis of variance, F-test, and the Wilcoxon rank-sum test.
Duration of Response	Up to 36 months	Number weeks until disease progression measured from Day-1 of study drug administration to disease progression.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Sorfenib + Paclitaxel Oral sorafenib tosylate twice daily on days 1-28 and paclitaxel IV over 1 hour on days 1, 8, and 15 paclitaxel: The chemotherapy drug called paclitaxel (Taxol) treats breast cancer, lung cancer, ovarian cancer and Kaposis sarcoma sorafenib tosylate: Sorafenib is a type of targeted therapy known as a kinase inhibitor used to treat advanced renal cell carcinoma and unresectable hepatocellular carcinoma	20
Total	20

Arm

Count

Sorfenib + Paclitaxel

Oral sorafenib tosylate twice daily on days 1-28 and paclitaxel IV over 1 hour on days 1, 8, and 15 paclitaxel: The chemotherapy drug called paclitaxel (Taxol) treats breast cancer, lung cancer, ovarian cancer and Kaposis sarcoma sorafenib tosylate: Sorafenib is a type of targeted therapy known as a kinase inhibitor used to treat advanced renal cell carcinoma and unresectable hepatocellular carcinoma

Total

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	1
Overall Study	Death	1
Overall Study	Withdrawal by Subject	2

Baseline characteristics

Characteristic	Sorfenib + Paclitaxel
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	2 Participants
Age, Categorical Between 18 and 65 years	18 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	17 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	10 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	10 Participants
Sex: Female, Male Female	19 Participants
Sex: Female, Male Male	1 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	1 / 16
other Total, other adverse events	11 / 16
serious Total, serious adverse events	0 / 16

Outcome results

Primary

Time to Tumor Progression

Progression-free survival was defined as the time of treatment to the earliest date of documentation of disease progression or death due to any cause. In the case of a participant started treatment. Tenth month of progression-free rate of sorafenib and paclitaxel will be compared agains the null progression free rate of 32% using normal approximation test.

Time frame: Time from first treatment to disease progression or death (up to 36 months)

Arm	Measure	Value (MEDIAN)
Sorfenib + Paclitaxel	Time to Tumor Progression	6.6 months

Secondary

Clinical Benefit Rate (Tumor Response and Stable Disease) at 24 Weeks

Number of patients with either complete response (CR) or partial response (PR) as defined in Response Evaluation Criteria in Solid Tumors (for patients with measurable disease). Complete Response: Disappearance of all target lesions, disappearance of all non-target lesions for at least 4 weeks. Partial Response: At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameters.

Time frame: 24 weeks