Clinical Trials /

Paclitaxel and Cyclophosphamide With or Without Trastuzumab Before Surgery in Treating Patients With Previously Untreated Breast Cancer

NCT01750073

Description:

This phase II trial studies the side effects and how well giving paclitaxel and cyclophosphamide with or without trastuzumab before surgery works in treating patients with previously untreated breast cancer. Drugs used in chemotherapy, such as paclitaxel and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as trastuzumab, may block tumor growth in different ways by targeting certain cells. Giving combination chemotherapy with or without trastuzumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Paclitaxel and Cyclophosphamide With or Without Trastuzumab Before Surgery in Treating Patients With Previously Untreated Breast Cancer
  • Official Title: A Phase II Study of Neoadjuvant Chemotherapy With and Without Trastuzumab in Patients With Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: 264-12
  • SECONDARY ID: NCI-2012-01372
  • SECONDARY ID: 264-12
  • SECONDARY ID: P30CA036727
  • NCT ID: NCT01750073

Conditions

  • Estrogen Receptor Negative
  • Estrogen Receptor Positive
  • HER2/Neu Negative
  • HER2/Neu Positive
  • Invasive Breast Carcinoma
  • Progesterone Receptor Negative
  • Progesterone Receptor Positive
  • Stage IA Breast Cancer
  • Stage II Breast Cancer
  • Stage IIA Breast Cancer
  • Stage IIB Breast Cancer
  • Stage III Breast Cancer
  • Stage IIIA Breast Cancer
  • Stage IIIB Breast Cancer
  • Stage IIIC Breast Cancer
  • Triple-Negative Breast Carcinoma

Interventions

DrugSynonymsArms
Cyclophosphamide(-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719Treatment (chemotherapy, surgery, post-operative therapy)
Doxorubicin Hydrochloride5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI), ADM, Adriacin, Adriamycin, Adriamycin Hydrochloride, Adriamycin PFS, Adriamycin RDF, ADRIAMYCIN, HYDROCHLORIDE, Adriamycine, Adriblastina, Adriblastine, Adrimedac, Chloridrato de Doxorrubicina, DOX, DOXO-CELL, Doxolem, Doxorubicin.HCl, Doxorubin, Farmiblastina, FI 106, FI-106, hydroxydaunorubicin, RubexTreatment (chemotherapy, surgery, post-operative therapy)
PaclitaxelAnzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol KonzentratTreatment (chemotherapy, surgery, post-operative therapy)
TrastuzumabABP 980, Anti-c-ERB-2, Anti-c-erbB2 Monoclonal Antibody, Anti-ERB-2, Anti-erbB-2, Anti-erbB2 Monoclonal Antibody, Anti-HER2/c-erbB2 Monoclonal Antibody, Anti-p185-HER2, c-erb-2 Monoclonal Antibody, HER2 Monoclonal Antibody, Herceptin, Herceptin Biosimilar PF-05280014, Herceptin Trastuzumab Biosimilar PF-05280014, MoAb HER2, Monoclonal Antibody c-erb-2, Monoclonal Antibody HER2, PF-05280014, rhuMAb HER2, RO0452317, Trastuzumab Biosimilar ABP 980, Trastuzumab Biosimilar PF-05280014Treatment (chemotherapy, surgery, post-operative therapy)

Purpose

This phase II trial studies the side effects and how well giving paclitaxel and cyclophosphamide with or without trastuzumab before surgery works in treating patients with previously untreated breast cancer. Drugs used in chemotherapy, such as paclitaxel and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as trastuzumab, may block tumor growth in different ways by targeting certain cells. Giving combination chemotherapy with or without trastuzumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To evaluate the toxicities and tolerability of a neoadjuvant dose-dense regimen
      cyclophosphamide and paclitaxel with or without trastuzumab/radiation therapy (as clinically
      indicated) in patients with newly diagnosed stage T1cN0 and II-III breast cancer; followed by
      maintenance trastuzumab in human epidermal growth factor receptor 2 (HER2) positive OR
      adriamycin (doxorubicin hydrochloride) followed by radiation therapy (RT) in stage II-III
      triple negative HER2 (-), estrogen receptor (ER) (-), progesterone receptor (PR) (-) stage
      T1cN0 and II-III breast cancer patients.

      II. To determine the pathological complete response rate (pCR) of this treatment regimen.

      III. To identify possible gene expression profile signatures from whole genome array analysis
      that correlate with clinical response/resistance to chemotherapy as measured by pathologic
      complete response rate (pCR).

      OUTLINE:

      NEOADJUVANT THERAPY: Patients receive paclitaxel intravenously (IV) over 3 hours and
      cyclophosphamide IV over 1 hour on day 1. Patients with HER2-positive cancer also receive
      trastuzumab IV over 30 minutes on day 1. Treatment repeats every 14 days for up to 6 courses
      in the absence of disease progression or unacceptable toxicity. Patients without metastasis
      undergo mastectomy or breast conserving surgery 4-8 weeks later.

      POST-SURGERY/SYSTEMIC THERAPY:

      HER2-POSITIVE PATIENTS: Patients receive standard radiation therapy. Patients also receive
      trastuzumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 13 courses
      in the absence of disease progression or unacceptable toxicity.

      ER/PR POSITIVE PATIENTS: Patients receive standard adjuvant hormonal or endocrine therapy.

      STAGE T1cN0 TRIPLE NEGATIVE PATIENTS: Patients receive standard radiation therapy.

      STAGE II-III TRIPLE NEGATIVE PATIENTS: Patients receive doxorubicin hydrochloride IV over 15
      minutes on day 1. Treatment repeats every 14 days for up to 4 courses in the absence of
      disease progression or unacceptable toxicity. Patients also receive standard radiation
      therapy.

      After completion of study treatment, patients are followed up every 3 months for 2 years, and
      then annually thereafter.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (chemotherapy, surgery, post-operative therapy)ExperimentalSee Detailed Description
  • Cyclophosphamide
  • Doxorubicin Hydrochloride
  • Paclitaxel
  • Trastuzumab

Eligibility Criteria

        Inclusion Criteria:

          -  Women with histologically proven invasive breast cancer without distant metastases; a
             clinical tumor classification of tumor size must be at least 1 cm with or without
             clinical pathologic evidence of positive nodes

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  At least one lesion that can be accurately measured in two dimensions utilizing
             mammogram, ultrasound, or magnetic resonance imaging (MRI) images to define specific
             size and validate complete clinical and pathologic response

          -  Patients who received radiation therapy > 5 years ago for malignancies other than
             breast cancer and whose radiation therapy field is not overlapping with the 20%
             isodose line of current radiation field are eligible, provided that radiation therapy
             was completed > 5 years ago and that there is no evidence of the second malignancy at
             the time of study entry

          -  Absolute neutrophil count greater than or equal to 1,500/mcl

          -  Platelet count equal to or greater than 150,000/mcl

          -  Alkaline phosphatase equal or less than 1.5 times the upper limit of normal (ULN)

          -  Total bilirubin equal to or less than 1.5 times the ULN

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) no greater than
             1.5 times the ULN

          -  Creatinine less than 1.5 times the ULN

          -  All included patients must have normal cardiac function as defined by an ejection
             fraction of >= 50% and no decrease in wall motion by echocardiogram

          -  The patient must be aware of the neoplastic nature of his/her disease and willingly
             provide written, informed consent after being informed of the procedure to be
             followed, the experimental nature of the therapy, alternatives, potential benefits,
             side-effects, risks, and discomforts

          -  Women of reproductive potential must be non-pregnant and non-nursing and must agree to
             employ an effective barrier method of birth control throughout the study and for up to
             6 months following treatment

          -  Women of child-bearing potential must have a negative pregnancy test within 7 days of
             initiating study; (no childbearing potential is defined as age 55 years or older and
             no menses for two years or any age with surgical removal of the uterus and/or both
             ovaries)

        Exclusion Criteria:

          -  Any patient with inflammatory breast cancer or stage IV or confirmed metastatic
             disease

          -  Patients who have had any prior chemotherapy, or endocrine therapy for the treatment
             of breast cancer or any other cancer

          -  Patients who cannot undergo surgery

          -  Patients with a known or documented anaphylactic reaction or allergy to any of
             chemotherapy agents used in this protocol, or to antiemetics appropriate for
             administration in conjunction with protocol-directed therapy

          -  Uncontrolled inter-current illness including, but not limited to ongoing or active
             infection requiring intravenous antibiotics, symptomatic congestive heart failure,
             unstable angina pectoris, or serious, uncontrolled cardiac arrhythmia, that might
             jeopardize the ability of the patient to receive the therapy program outlined in this
             protocol with reasonable safety

          -  Patients with preexisting grade II peripheral neuropathy

          -  Pregnant and nursing women are excluded from this study

          -  Patients with prior malignancy will be excluded except for adequately treated basal
             cell or squamous cell skin cancer, adequately treated noninvasive carcinomas

          -  Inability to cooperate with treatment protocol

          -  Patients with known human immunodeficiency virus (HIV) infection, infectious
             hepatitis, type A, B or C, active hepatitis, or hepatic insufficiency

          -  Patients may not be receiving or have received any other investigational agents
             during/or within 1 month prior

          -  Any serious medical condition, laboratory abnormality, or psychiatric illness that
             would prevent the subject from signing the informed consent form

          -  Myocardial infarction within 6 months prior to enrollment or has New York Heart
             Association (NYHA) class III or IV heart failure uncontrolled angina, severe
             uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
             ischemia or active conduction system abnormalities; prior to study entry, any
             electrocardiogram (ECG) abnormality at screening has to be documented by the
             investigator as not medically relevant
      
Maximum Eligible Age:N/A
Minimum Eligible Age:19 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall incidence of toxicities, graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Time Frame:Up to 30 days after completion of study treatment
Safety Issue:
Description:Adverse events will be tallied for overall frequency (number and percentage of subjects), and relationship to study drugs. Serious adverse events will be summarized similarly. Listings of deaths, serious adverse events (SAEs) and adverse events (AEs) leading to early termination of study treatment or premature withdrawal from study will also be provided. Analyses will be reported overall and for HER+ and HER- subsets.

Secondary Outcome Measures

Measure:Clinical complete response
Time Frame:Up to 2 years
Safety Issue:
Description:
Measure:Failure-free survival (FFS)
Time Frame:The time from the date of administration of study drug to the date of first appearance of tumor lesions by imaging, or death, assessed up to 2 years
Safety Issue:
Description:The analysis will be based on Kaplan-Meier estimates. FFS will be summarized overall and for HER+ and HER- subsets.
Measure:Identification of gene expression profile signatures that correlate with clinical response as measured by pCR
Time Frame:Up to 2 years
Safety Issue:
Description:The number of the identified mutated genes, the frequency of each gene being validated by reverse transcriptase-polymerase chain reaction (RT-PCR)/Sanger sequencing method, and the functions of these identified genes will be descriptively summarized.
Measure:Overall survival (OAS)
Time Frame:The time from the date of the date of administration of study drug to the date of death from any cause, assessed up to 2 years
Safety Issue:
Description:The analysis will be based on Kaplan-Meier estimates. OAS will be summarized overall and for HER+ and HER- subsets.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Nebraska

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