Phase 2
N=64
Abraxane With or Without Tigatuzumab in Patients With Metastatic, Triple Negative Breast Cancer
Breast Cancer · Triple Negative Breast Cancer · Stage IV Breast Cancer · Metastatic Breast Cancer
Bottom Line
View on ClinicalTrials.gov: NCT01307891 ↗Enrolled (actual)
64
Serious AEs
10.0%
Results posted
Sep 2017
Primary outcome: Primary: Objective Response Rate — 28; 38 percentage of patients
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Abraxane alone (Drug); Abraxane + Tigatuzumab (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- University of Alabama at Birmingham
- Primary completion
- Jun 2016
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Objective Response Rate |
28; 38 | — |
| SECONDARY Number of Participants With Serious Adverse Events |
0; 0 | — |
| SECONDARY Progression-free Survival |
2.8; 3.8 | — |
Summary
Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer deaths in American women. Metastatic disease including metastatic breast cancer unfortunately remains incurable. One reason is due to the inability to develop specific therapies for specific cancer subsets.
The use of modern genomic techniques has significantly enhanced our recent understanding of breast cancer biology. Five distinct breast cancer subsets have been recognized, one of which is basal-like breast cancer. Basal-like breast cancer is typically estrogen receptor (ER) negative, progesterone receptor (PR) negative and human epidermal growth factor receptor 2 (HER-2-Neu) negative. This is referred to as triple negative breast cancer or TBNC. TBNC represents a significant proportion of breast cancer patients (10-20%) and has a poor prognosis with no targeted approach to therapy as of yet.
Tigatuzumab is a humanized monoclonal antibody targeting a death receptor on the breast cancer cells. Previous studies have shown that combining antibodies with selected chemotherapy agents have induced tumor cell death. The hypothesis of this study is to use tigatuzumab and combine it with Abraxane to serve as a targeting agent in metastatic TBNC patients.
Eligibility Criteria
Inclusion Criteria
- Patients must have pathologically documented Stage IV breast cancer. If blocks (paraffin-embedded tissue) from original diagnosis are available, they will be obtained to confirm the diagnosis and for correlative studies. Fifteen slides can be obtained from the block if the block is not available to be sent or released.
- Tumor must be HER-2-neu negative (defined as 0 or 1+ staining by immunohistochemistry or gene amplification ratio less than or equal to 2.0, by fluorescent in situ hybridization - FISH), estrogen and progesterone receptors negative ( or equal to 1,500/mcL,
- Hemoglobin: > or equal to 9 mg/dL,
- Platelets: > or equal to 100,000/mcL,
- Total bilirubin: < or equal to 1.5 X institutional upper limit of normal,
- AST(SGOT)/ALT(SGPT): < or equal to 2.5 X institutional upper limit of normal without liver metastases, OR < or equal to 5 X institutional upper limit of normal if documented liver metastases,
- Creatinine: < or equal to 2.0 mg/dL, OR calculated creatinine clearance greater than or equal to 50 mL/min (calculated by the Cockcroft and Gault method).
- Ability to understand and the willingness to sign a written informed consent document.
- Both men and women are eligible.
- Use of an effective means of contraception in subjects of child-bearing potential.
- Negative serum or urine beta-HCG pregnancy test at screening for patients with childbearing potential.
Exclusion Criteria
- Patients may not be receiving any other investigational agents.
- Prior use of Abraxane for metastatic disease or in the adjuvant setting.
- Metastatic lesions identifiable only by PET.
- Patients may not be receiving concurrent chemotherapy for treatment of metastatic disease.
- Active brain metastases: evidence of progression < or equal to 3 months after local therapy (patients should be asymptomatic and off corticosteroids and anticonvulsants for at least 3 months prior to study entry).
- Patients with brain metastases must have at least one site of measurable disease outside of the central nervous system.
- Uncontrolled concurrent illness including, but not limited to, ongoing or active infection, history of recent myocardial infarction, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant or lactating women are excluded. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother, breastfeeding should be discontinued if the mother is treated. These potential risks may also apply to other agents used in this study.
- A prior invasive malignant disease within five years except for skin cancer (squamous cell or basal cell carcinoma).
- Patients with known history of HIV or Hepatitis B because of potential for added toxicity from treatment regimen.
- Dementia or altered mental status that would prohibit the understanding of informed consent.
Data sourced from ClinicalTrials.gov (NCT01307891). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.