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Phase II Prospective Open Label Single Arm Study of Pertuzumab, Trastuzumab, and Nab-Paclitaxel in Patients With HER-2 Positive Metastatic Breast Cancer

Phase 2
19 Years
Not Enrolling
HER2-positive Breast Cancer, Male Breast Cancer, Recurrent Breast Cancer, Stage IV Breast Cancer

Thank you

Trial Information

Phase II Prospective Open Label Single Arm Study of Pertuzumab, Trastuzumab, and Nab-Paclitaxel in Patients With HER-2 Positive Metastatic Breast Cancer


I. To determine the preliminary efficacy of administration of pertuzumab in combination with
trastuzumab with nab-paclitaxel (paclitaxel albumin-stabilized nanoparticle formulation) in
subjects with stage IV HER-2 overexpressing breast cancer as measured by progression free
survival (PFS).


I. To evaluate the safety of pertuzumab when added to trastuzumab and abraxane (paclitaxel
albumin-stabilized nanoparticle formulation) in stage IV HER-2 overexpressing breast cancer
assessed by the frequency and severity of adverse events (AEs), abnormal findings on
physical examination, laboratory tests, and vital signs.

II. To evaluate the objective response rate and duration of response. III. To evaluate the
objective tumor response (Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1
criteria) where possible.

IV. To assess the overall survival.


Patients receive pertuzumab intravenously (IV) over 30-60 minutes on day 1, trastuzumab IV
over 30-90 minutes and paclitaxel albumin-stabilized nanoparticle formulation IV over 30
minutes on days 1, 8, and 15. Courses repeat every 21 days in the absence of disease
progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 4 years and
then every 6 months for 1 year.

Inclusion Criteria:

- Patients must be diagnosed with metastatic cytologically or histologically confirmed
adenocarcinoma of the breast with HER2 over-expression; patients must have measurable
and/or evaluable lesions

- The effects of the proposed therapeutic agents (pertuzumab, nab-paclitaxel,
trastuzumab) on the developing fetus are unknown; for this reason, women of
child-bearing potential and men must agree to use adequate contraception (hormonal or
barrier method of birth control or abstinence) prior to study entry and for six
months following duration of study participation; should a woman become pregnant or
suspect that she is pregnant while participating on the trial, she should inform her
treating physician immediately

- Tumor positive or negative for expression of hormone receptors (< 1% or > 1%) and
overexpressing HER2 by immunohistochemistry (IHC), or, in case of IHC of 2, positive
by fluorescence in situ hybridization (FISH) >= 2 or by alternative gene testing

- Prior adjuvant chemotherapy and trastuzumab more than or equal to 6 months prior to
enrollment are allowed

- No prior chemotherapy or trastuzumab for treatment of metastatic breast cancer

- Left ventricular ejection fraction (LVEF) >= 50% (determined by echocardiogram or
multigated acquisition scan) within 42 days of treatment

- Eastern Cooperative Oncology Group performance status of 0 or 1

- Prior radiotherapy is allowed provided that there is documentation of progression
(either locally or systemically)

- Patients may have had prior chemotherapy in the adjuvant setting

- Toxic effects from prior therapy must have resolved to grade 1 or less except for
peripheral neuropathy and alopecia

- Hemoglobin >= 90 g/L

- Leukocytes >= 3.0 x 10^9/L

- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L

- Platelets >= 100 x 10^9/L

- Total bilirubin =< 1.3 mg/dl (institutional upper limit of normal)

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 2 x institutional upper limit of normal (=< 5 times the upper limit of normal
[ULN] for patients with liver metastases)

- Creatinine within normal institutional limits or creatinine clearance > 50
mL/min/1.73 m^2 for patients with creatinine levels above institutional normal (using
Cockcroft-Gault formula)

- All radiology studies must be performed =< 4 weeks prior to the start of therapy

- No serious medical conditions such as myocardial infarction within 6 months prior to
entry, congestive heart failure, unstable ventricular arrhythmia, uncontrolled
hypertension, uncontrolled diabetes mellitus, uncontrolled psychotic disorders,
serious infections, active peptic ulcer disease, psychiatric illness, or any other
medical conditions that might be aggravated by treatment or limit compliance

- Currently, no active second malignancy other than non-melanoma skin cancer; Note:
patients are not considered to have a "current active" malignancy if they have
completed anti-cancer therapy and are considered by their physicians to have a less
than 30% chance of relapse

- All patients must have the ability to understand and the willingness to sign an
informed consent

- Negative serum or urine beta-human chorionic gonadotropin (hCG) pregnancy test at
screening for patients of child-bearing potential

- No prior therapies (except for anti-estrogen therapy) are allowed for the treatment
of the newly diagnosed metastatic breast cancer; patients are allowed to have had
prior chemotherapy for breast cancer in the adjuvant setting for at least 6 months
prior to enrollment into this study; patients with a prior diagnosis of malignancy
treated >= 5 years ago are eligible, provided that they have not received prior
nab-paclitaxel as part of their prior treatment regimen, and that they meet all
eligibility criteria

Exclusion Criteria:

- Known active hepatitis B or C (due to the potential for disease treatment-related
pharmacological and liver function-specific interactions)

- Known active human immunodeficiency virus (HIV) (due to the complexity and potential
pharmacological interactions between the standard neoadjuvant therapeutic agents, and
highly active antiretroviral therapy [HAART])

- Prior breast cancer or other invasive malignancy treated within 5 years

- Pregnancy

- Neuropathy > grade 1

- Any other intercurrent medical/psychological problem deemed exclusionary by the
treating physician or investigators/principal investigator (PI)

- Recurrence < 6 months since completion of adjuvant treatment

- Prior chemotherapy or trastuzumab treatment for metastatic disease

- Cumulative dose of doxorubicin or equivalent of > 360 mg/m^2 during prior adjuvant

- LVEF < 50% during previous trastuzumab therapy

- Central nervous system metastases

- Another malignancy excluding basal cell skin cancer

- Hemoglobin < 9 g/dL

- ANC < 1500/mcL

- Platelet < 100,000/mcL

- Creatinine clearance =< 50 mL/min as measured by either the Cockcroft-Gault method or
24-hour creatinine clearance)

- AST (SGOT)/ALT (SGPT) > 2 x institutional upper limit of normal

- Uncontrolled hypertension or unstable angina, congestive heart failure (New York
Heart Association classification), or myocardial infarction within 6 months of

- Pregnant women

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression free survival

Outcome Description:

Estimated by the Kaplan-Meier method.

Outcome Time Frame:

Time from initiation of treatment until objective disease progression, assessed up to 5 years

Safety Issue:


Principal Investigator

George Somlo, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

City of Hope Medical Center


United States: Federal Government

Study ID:




Start Date:

June 2013

Completion Date:

Related Keywords:

  • HER2-positive Breast Cancer
  • Male Breast Cancer
  • Recurrent Breast Cancer
  • Stage IV Breast Cancer
  • Breast Neoplasms
  • Breast Neoplasms, Male



City of Hope Medical CenterDuarte, California  91010
City of Hope- South Pasadena Cancer CenterSouth Pasadena, California  91030