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An Open Label, Randomized, Phase II Trial of Abraxane (Paclitaxel Albumin-Bound Particles for Injectable Suspension), With or Without Tigatuzumab (a Humanized Monoclonal Antibody Targeting Death Receptor 5) in Patients With Metastatic, Triple Negative (ER, PR, and HER-2 Negative) Breast Cancer

Phase 2
18 Years
Open (Enrolling)
Breast Cancer, Triple Negative Breast Cancer, Stage IV Breast Cancer, Metastatic Breast Cancer

Thank you

Trial Information

An Open Label, Randomized, Phase II Trial of Abraxane (Paclitaxel Albumin-Bound Particles for Injectable Suspension), With or Without Tigatuzumab (a Humanized Monoclonal Antibody Targeting Death Receptor 5) in Patients With Metastatic, Triple Negative (ER, PR, and HER-2 Negative) Breast Cancer

The study is an open-label randomized, multi-institutional, phase II clinical trial of
Abraxane in combination with tigatuzumab or Abraxane as a single agent in patients with
TNBC. Randomization (2:1) will be made from these two categories: TBNC patients with no
prior chemotherapy for metastatic disease or TBNC patients with prior taxane (except
Abraxane) therapy for metastatic disease. Patients randomized to Abraxane alone may be
allowed to cross over to the combination of Abraxane + tigatuzumab if there is disease

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 (<10%).

- Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded)

- Biopsy of a metastatic lesion is not required for protocol entry but all patients
with reasonably accessible lesions (chest wall, breast, skin, subcutaneous,
superficial lymph nodes, bones and liver metastases) must agree to biopsy.

1. Biopsies may be done with local anesthesia or intravenous conscious sedation,
according to standard institutional guidelines.

2. If a biopsy requires general anesthesia, then it is only allowed if acquisition
of tissue is necessary for clinical reasons and excess tissue that would
otherwise have been discarded is then used for research purposes. If a biopsy
requires general anesthesia, then a biopsy of that site for research purposes
only, without a coexisting clinical indication is not allowed on this protocol.

3. Patients with reasonably accessible lesions as described above, who will not
agree with the biopsy, will not be enrolled in the trial.

4. Patients with NO reasonably accessible lesions as described above can be
enrolled in the trial.

Prior Therapy:

- There is no restriction as to the number of prior regimens for metastatic disease as
long as patients have adequate performance status. Patients with no prior
chemotherapy for metastatic disease and patients who have received prior therapy with
taxanes for metastatic disease (taxol or taxotere) are eligible. Stratification will
be used for randomization of these two categories (no prior chemotherapy for
metastatic disease or prior taxane therapy for metastatic disease).

- Chemotherapy treatment prior to enrollment must be discontinued for at least 3 weeks
prior to study entry.

- Patients must have completed radiation therapy at least 7 days prior to beginning
protocol treatment.

- Patients must have recovered from all reversible toxicities related to prior therapy
before beginning protocol treatment, and may not have any pre- existing
treatment-related toxicities in excess of grade 1. Patients must have < grade 2
pre-existing peripheral neuropathy.

- Patients may receive bisphosphonates; however, if used, bone lesions may not be used
for progression or response.

- At least 18 years of age (19 in Alabama).

- Life expectancy of greater than 12 weeks.

- ECOG performance status < or equal to 2.

- Patients must have normal organ and marrow function as defined below:

- Absolute neutrophil count: > 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

- 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

- 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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Objective response rate

Outcome Description:

The primary endpoint of this trial is the objective response rate as measured by complete responses and partial responses for the combination of tigatuzumab and Abraxane or Abraxane alone in patients with metastatic triple negative breast cancer. This information will be used to generate hypotheses for further trials.

Outcome Time Frame:

Interim analysis will be conducted after 11 patients have been accrued and completed in each arm. Final analysis will be at the conclusion of the study: about 2 years.

Safety Issue:


Principal Investigator

Andres Forero, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Alabama at Birmingham


United States: Food and Drug Administration

Study ID:

F101004001 (UAB1028)



Start Date:

March 2011

Completion Date:

March 2015

Related Keywords:

  • Breast Cancer
  • Triple Negative Breast Cancer
  • Stage IV Breast Cancer
  • Metastatic Breast Cancer
  • Triple negative breast cancer (TNBC)
  • Metastatic breast cancer
  • Tigatuzumab (CS-1008)
  • Abraxane (ABI-007)
  • HER-2-neu negative
  • ER negative, PR negative
  • Breast Neoplasms



Memorial Sloan Kettering Cancer CenterNew York, New York  10021
University of Michigan Comprehensive Cancer CenterAnn Arbor, Michigan  48109-0752
Indiana University Melvin and Bren Simon Cancer CenterIndianapolis, Indiana  46202-5289
Baylor UniversityWaco, Texas  
Vanderbilt UniversityNashville, Tennessee  37232-6305
University of North CarolinaChapel Hill, North Carolina  27599
University of ChicagoChicago, Illinois  60637
Georgetown University Medical CenterWashington, District of Columbia  20007
University of Alabama at Birmingham (UAB)Birmingham, Alabama  35233
Dana Farber Cancer Center InstituteBoston, Massachusetts  02215