<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01697293</url>
  </required_header>
  <id_info>
    <org_study_id>2011-269</org_study_id>
    <secondary_id>NCI-2013-01311</secondary_id>
    <secondary_id>11-051</secondary_id>
    <secondary_id>TCN-PM</secondary_id>
    <secondary_id>PTX-200-BC-1501.1</secondary_id>
    <secondary_id>PTX-200</secondary_id>
    <secondary_id>007884</secondary_id>
    <secondary_id>2011-269</secondary_id>
    <secondary_id>P30CA013330</secondary_id>
    <secondary_id>R01CA098473</secondary_id>
    <nct_id>NCT01697293</nct_id>
  </id_info>
  <brief_title>PTX-200, Paclitaxel, Doxorubicin Hydrochloride, and Cyclophosphamide in Treating Patients With Stage IIB-IV Breast Cancer</brief_title>
  <official_title>A Phase I-II Study of PTX-200 Plus Sequential Weekly Paclitaxel Followed by Dose-Dense Doxorubicin and Cyclophosphamide in Patients With Metastatic and Locally Advanced Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Prescient Therapeutics, Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Prescient Therapeutics, Ltd.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase I/II trial studies the side effects and the best dose of triciribine phosphate&#xD;
      when given together with paclitaxel, doxorubicin hydrochloride, and cyclophosphamide and to&#xD;
      see how well they work in treating patients with stage IIB-IV breast cancer. Triciribine&#xD;
      phosphate may stop the growth of tumor cells by blocking some of the enzymes needed for cell&#xD;
      growth. Drugs used in chemotherapy, such as paclitaxel, doxorubicin hydrochloride, and&#xD;
      cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing&#xD;
      the cells, by stopping them from dividing, or by stopping them from spreading. Giving&#xD;
      triciribine phosphate with paclitaxel, doxorubicin hydrochloride, and cyclophosphamide may be&#xD;
      a better treatment for breast cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To determine the recommended phase II dose of PTX-200 (triciribine phosphate) given on&#xD;
      days 1, 8, and 15 every 28 days (maximum of 9 doses) when combined with weekly paclitaxel (80&#xD;
      mg/m^2) for 12 weeks in patients with metastatic breast cancer. (Phase I and Expansion&#xD;
      Cohort) II. To determine the pathologic response rate (Residual Cancer Burden [RCB] score&#xD;
      0-1) after sequential weekly paclitaxel plus PTX 200 weekly, 3 weeks out of 4, followed by&#xD;
      doxorubicin (doxorubicin hydrochloride) (60 mg/m^2) and cyclophosphamide (600 mg/m^2) every 2&#xD;
      weeks x 4 cycles in patients with clinical stage IIB-IIIC breast cancer. (Phase II).&#xD;
&#xD;
      III. To determine the feasibility and safety of the combination of sequential weekly&#xD;
      paclitaxel plus PTX-200 (days 1, 8, and 15) followed by doxorubicin/cyclophosphamide. (Phase&#xD;
      II)&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To correlate pre-treatment levels of erb-b2 receptor tyrosine kinase (ErbB)1, 2, 3, 4 and&#xD;
      zinc finger protein 217 (ZNF217), and phosphorylated levels of v-akt murine thymoma viral&#xD;
      oncogene homolog 1 (Akt), signal transducer and activator of transcription 3 (acute-phase&#xD;
      response factor) (STAT3), extracellular signal-regulated protein kinases 1 and 2 (Erk1/2) to&#xD;
      pathologic (RCB score 0-1) response (Sebti laboratory [lab]). (Phase I or II) II. To&#xD;
      correlate the percent decrease in the levels of phosphorylated (phospho-)Akt (S473),&#xD;
      phospho-S6 (S235-236), phospho-proline-rich Akt substrate, 40 kDa (PRAS40) (threonine&#xD;
      [Thr]246), phosphatase and tensin homolog (PTEN), Stathmin, pyruvate dehydrogenase kinase,&#xD;
      isozyme 1 (PDK1), cyclin D1, phospho-STAT3, ras homolog gene family, member C (Rho C), and&#xD;
      phospho-Erk 1-2 with pathologic response rate (RCB score 0-1), percent inhibition of&#xD;
      proliferation (Ki-67) and percent induction of apoptosis (terminal deoxynucleotidyl&#xD;
      transferase dUTP nick end labeling [Tunel]) (Sebti lab). (Phase I or II)&#xD;
&#xD;
      OUTLINE: This is a phase I, dose-escalation study of triciribine phosphate followed by an&#xD;
      expansion cohort and a phase II study.&#xD;
&#xD;
      COURSES A 1-12 (PHASE I &amp; II): Patients receive triciribine phosphate intravenously (IV) over&#xD;
      60 minutes on days 1, 8, and 15, 29, 36, 43, 57, 64, and 71 and paclitaxel IV over 1 hour on&#xD;
      days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 79. Treatment repeats every week for 12&#xD;
      courses in the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      COURSES B 1-4 (PHASE II): Patients receive doxorubicin hydrochloride IV over 5-10 minutes and&#xD;
      cyclophosphamide IV over 30-60 minutes on day 1. Treatment repeats every 14 days for 4&#xD;
      courses in the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      SURGERY (PHASE II): Eligible patients undergo modified radical mastectomy, radical&#xD;
      mastectomy, segmental mastectomy or lumpectomy with an axillary lymph node dissection or&#xD;
      biopsy.&#xD;
&#xD;
      After completion of study treatment, patients with metastatic disease are followed up every 3&#xD;
      months for 1 year and patients with locally advanced disease are followed up every 6 months&#xD;
      for 2 years and then yearly for 3 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    criteria for continuing enrollment in Phase 2 portion was not met&#xD;
  </why_stopped>
  <start_date type="Actual">January 2012</start_date>
  <completion_date type="Actual">June 2020</completion_date>
  <primary_completion_date type="Actual">June 2020</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pathologic response (RCB score 0-1), assessed using the criteria of Chevallier (Phase II)</measure>
    <time_frame>At time of surgery</time_frame>
    <description>The estimated pCR along with exact confidence interval will be presented.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Recommended phase II dose of triciribine phosphate, based on the incidence of dose-limiting toxicity graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (Phase I)</measure>
    <time_frame>28 days</time_frame>
    <description>Adverse effects will be summarized using frequency tables. The proportion of patients who completed all 12 courses of paclitaxel (at full dose or with dose modification) will be tabulated.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical complete response and partial response, based on tumor measurements obtained by physical exam</measure>
    <time_frame>Up to 20 weeks (completion of courses B 1-4)</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">34</enrollment>
  <condition>Breast Adenocarcinoma</condition>
  <condition>Estrogen Receptor Positive</condition>
  <condition>HER2/Neu Negative</condition>
  <condition>Recurrent Breast Carcinoma</condition>
  <condition>Stage IIB Breast Cancer</condition>
  <condition>Stage IIIA Breast Cancer</condition>
  <condition>Stage IIIB Breast Cancer</condition>
  <condition>Stage IIIC Breast Cancer</condition>
  <condition>Stage IV Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Treatment (chemotherapy, surgery)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>COURSES A 1-12 (PHASE I &amp; II): Patients receive triciribine phosphate IV over 60 minutes on days 1, 8, and 15, 29, 36, 43, 57, 64, and 71 and paclitaxel IV over 1 hour on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 79. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity.&#xD;
COURSES B 1-4 (PHASE II): Patients receive doxorubicin hydrochloride IV over 5-10 minutes and cyclophosphamide IV over 30-60 minutes on day 1. Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.&#xD;
SURGERY (PHASE II): Eligible patients undergo modified radical mastectomy, radical mastectomy, segmental mastectomy or lumpectomy with an axillary lymph node dissection or biopsy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (chemotherapy, surgery)</arm_group_label>
    <other_name>(-)-Cyclophosphamide</other_name>
    <other_name>2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate</other_name>
    <other_name>Carloxan</other_name>
    <other_name>Ciclofosfamida</other_name>
    <other_name>Ciclofosfamide</other_name>
    <other_name>Cicloxal</other_name>
    <other_name>Clafen</other_name>
    <other_name>Claphene</other_name>
    <other_name>CP monohydrate</other_name>
    <other_name>CTX</other_name>
    <other_name>CYCLO-cell</other_name>
    <other_name>Cycloblastin</other_name>
    <other_name>Cycloblastine</other_name>
    <other_name>Cyclophospham</other_name>
    <other_name>Cyclophosphamid monohydrate</other_name>
    <other_name>Cyclophosphamidum</other_name>
    <other_name>Cyclophosphan</other_name>
    <other_name>Cyclophosphane</other_name>
    <other_name>Cyclophosphanum</other_name>
    <other_name>Cyclostin</other_name>
    <other_name>Cyclostine</other_name>
    <other_name>Cytophosphan</other_name>
    <other_name>Cytophosphane</other_name>
    <other_name>Cytoxan</other_name>
    <other_name>Fosfaseron</other_name>
    <other_name>Genoxal</other_name>
    <other_name>Genuxal</other_name>
    <other_name>Ledoxina</other_name>
    <other_name>Mitoxan</other_name>
    <other_name>Neosar</other_name>
    <other_name>Revimmune</other_name>
    <other_name>Syklofosfamid</other_name>
    <other_name>WR- 138719</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Doxorubicin Hydrochloride</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (chemotherapy, surgery)</arm_group_label>
    <other_name>5,12-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)</other_name>
    <other_name>ADM</other_name>
    <other_name>Adriacin</other_name>
    <other_name>Adriamycin</other_name>
    <other_name>Adriamycin Hydrochloride</other_name>
    <other_name>Adriamycin PFS</other_name>
    <other_name>Adriamycin RDF</other_name>
    <other_name>ADRIAMYCIN, HYDROCHLORIDE</other_name>
    <other_name>Adriamycine</other_name>
    <other_name>Adriblastina</other_name>
    <other_name>Adriblastine</other_name>
    <other_name>Adrimedac</other_name>
    <other_name>Chloridrato de Doxorrubicina</other_name>
    <other_name>DOX</other_name>
    <other_name>DOXO-CELL</other_name>
    <other_name>Doxolem</other_name>
    <other_name>Doxorubicin.HCl</other_name>
    <other_name>Doxorubin</other_name>
    <other_name>Farmiblastina</other_name>
    <other_name>FI 106</other_name>
    <other_name>FI-106</other_name>
    <other_name>hydroxydaunorubicin</other_name>
    <other_name>Rubex</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (chemotherapy, surgery)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paclitaxel</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (chemotherapy, surgery)</arm_group_label>
    <other_name>Anzatax</other_name>
    <other_name>Asotax</other_name>
    <other_name>Bristaxol</other_name>
    <other_name>Praxel</other_name>
    <other_name>Taxol</other_name>
    <other_name>Taxol Konzentrat</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Therapeutic Conventional Surgery</intervention_name>
    <description>Undergo modified radical mastectomy, radical mastectomy, segmental mastectomy or lumpectomy with an axillary lymph node dissection or biopsy</description>
    <arm_group_label>Treatment (chemotherapy, surgery)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Triciribine Phosphate</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (chemotherapy, surgery)</arm_group_label>
    <other_name>1, 5-Dihydro-5-methyl-1-(5-O-phosphono-.beta.-D-ribofuranosyl)-1,4,5, 6,8-pentaazaacenaphthylen-3-amine</other_name>
    <other_name>1,4, 5,6,8-Pentaazaacenaphthylen-3-amine, 1, 5-dihydro-5-methyl-1-(5-O-phosphono-.beta.-D-ribofuranosyl)- (9CI)</other_name>
    <other_name>1,4,5,6, 8-Pentaazaacenaphthalen-3-amine, 1, 5-dihydro-5-methyl-1-(5-O-phosphono-.beta.-D-ribofuranosyl)-</other_name>
    <other_name>3-Amino-1, 5-dihydro-5-methyl-1-.beta.-D-ribofuranosyl-1,4,5,6, 8-pentaazaacenaphthylene 5'-(dihydrogen phosphate)</other_name>
    <other_name>TCN</other_name>
    <other_name>Triciribine</other_name>
    <other_name>Tricycloside Phosphate</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Phase I and expansion cohort: Patients must have histologically or cytologically&#xD;
             confirmed adenocarcinoma of the breast associated with clinical stage: IV (see&#xD;
             American Joint Committee on Cancer [AJCC] staging criteria, 7th edition) or stage&#xD;
             IIB-IIIC (expansion cohort only)&#xD;
&#xD;
          -  Phase II: Patients must have histologically or cytologically confirmed adenocarcinoma&#xD;
             of the breast associated with the following clinical stage: IIB, IIIA, IIIB, or IIIC&#xD;
             (see AJCC staging criteria, 7th edition); the tumor must be human epidermal growth&#xD;
             factor receptor 2 (Her2)/neu negative (by DAKO HercepTest, fluorescence based in situ&#xD;
             hybridization [FISH], or other approved assay)&#xD;
&#xD;
          -  Phase I and expansion cohort: Up to two prior non-taxane chemotherapy regimens for&#xD;
             metastatic disease are permitted for patients enrolled on the phase I portion of the&#xD;
             trial; patients with HER2/neu positive breast cancer are not eligible; patients&#xD;
             treated with prior anthracycline therapy as neoadjuvant, adjuvant, or metastatic&#xD;
             therapy are not eligible unless the following conditions are met: (a) prior cumulative&#xD;
             doxorubicin dose is =&lt; 240 mg/m^2 (or epirubicin dose is =&lt; 400 mg/m^2), and (b) left&#xD;
             ventricular ejection fraction (LVEF) obtained at baseline is at least 50% (or &gt;= 5%&#xD;
             above lower institutional limits of normal whichever is higher); patients with&#xD;
             estrogen receptor (ER)-positive disease are required to have relapse or progression on&#xD;
             at least one line of endocrine therapy&#xD;
&#xD;
          -  Phase II: No prior chemotherapy, irradiation, or definitive therapeutic surgery (e.g.,&#xD;
             mastectomy or lumpectomy or axillary dissection) for this malignancy; patients who&#xD;
             have had a prior sentinel lymph node biopsy for this malignancy are eligible&#xD;
&#xD;
          -  Patients who received tamoxifen or another selective estrogen receptor modulator&#xD;
             (SERM) for prevention or treatment of breast cancer or for other indications (e.g.,&#xD;
             osteoporosis, prior ductal carcinoma in situ [DCIS]), or who receive aromatase&#xD;
             inhibitors for prevention or treatment of breast cancer, are eligible; patients who&#xD;
             are hormone-receptor positive and who have received other hormonal agents for the&#xD;
             treatment of breast cancer (e.g., Fulvestrant) are also eligible; tamoxifen therapy or&#xD;
             other hormonal agents should be discontinued at least 1 week before the patient is&#xD;
             enrolled on this study&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1&#xD;
&#xD;
          -  Leukocytes &gt;= 3,000/uL&#xD;
&#xD;
          -  Absolute neutrophil count =&lt; 1,500/uL&#xD;
&#xD;
          -  Platelets &gt;= 100,000/uL&#xD;
&#xD;
          -  Total bilirubin within normal institutional limits&#xD;
&#xD;
          -  Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =&lt; 2.5 x institutional&#xD;
             upper limit of normal&#xD;
&#xD;
          -  Left ventricular ejection fraction (LVEF) within normal institutional limits&#xD;
&#xD;
          -  Creatinine within normal institutional limits&#xD;
&#xD;
          -  LVEF at or above institutional lower limits of normal (&gt;= 50%), or at least 5% above&#xD;
             lower limits of normal if prior anthracycline exposure (by echocardiogram or nuclear&#xD;
             scan within 12 weeks of registration)&#xD;
&#xD;
          -  Electrocardiogram (ECG) corrected QT (QTC) &lt; 450 msec&#xD;
&#xD;
          -  Serum calcium within normal institutional limits&#xD;
&#xD;
          -  Serum phosphorus within normal institutional limits&#xD;
&#xD;
          -  Fasting glucose within normal limits&#xD;
&#xD;
          -  Patients must be disease-free of prior invasive malignancies for &gt;= 2 years with the&#xD;
             exception of curatively-treated basal cell or squamous cell carcinoma of the skin,&#xD;
             carcinoma in situ of the cervix (for phase II only); patients with the following prior&#xD;
             or concurrent diagnoses are eligible: lobular carcinoma in situ, contralateral ductal&#xD;
             carcinoma in situ, or contralateral invasive ductal and/or lobular cancer (and no&#xD;
             prior adjuvant chemotherapy for previous breast malignancy)&#xD;
&#xD;
          -  Women of childbearing potential must agree to use adequate contraception (hormonal or&#xD;
             barrier method of birth control) prior to study entry and for the duration of study&#xD;
             participation; should a woman become pregnant or suspect she is pregnant while&#xD;
             participating in this study, she should inform her treating physician immediately&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients may not be receiving any other investigational agents during protocol&#xD;
             therapy, or up to 30 days prior to beginning protocol therapy; there should be a least&#xD;
             a 1-week interval between last dose of endocrine therapy and protocol therapy, and at&#xD;
             least 3 weeks for the last dose of biologic therapy (eg, bevacizumab) or cytotoxic&#xD;
             therapy (or 2 weeks for capecitabine or weekly paclitaxel, 6 weeks for mitomycin-C and&#xD;
             nitrosoureas), and adequately recovered from adverse effects from prior therapy to&#xD;
             meet all other eligibility criteria&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition to PTX-200 or other agents used in the study (e.g., imidazoles,&#xD;
             quinolones)&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, diabetes mellitus requiring therapy (insulin or oral hypoglycemic agents),&#xD;
             congenital prolonged QT syndrome, requirement for a drug known to prolong the QT&#xD;
             interval, a history of QT prolongation, a screening QTc &gt;= 450 msec,&#xD;
             hypertriglyceridemia requiring therapy, symptomatic congestive heart failure, unstable&#xD;
             angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that&#xD;
             would limit compliance with study requirements&#xD;
&#xD;
          -  Pregnant women are excluded from this study; breastfeeding should be discontinued if&#xD;
             the mother is treated with PTX-200; these potential risks may also apply to other&#xD;
             agents used in this study&#xD;
&#xD;
          -  Human immunodeficiency virus (HIV)-positive patients receiving combination&#xD;
             antiretroviral therapy are excluded from the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Joseph Sparano</last_name>
    <role>Principal Investigator</role>
    <affiliation>Albert Einstein College of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Moffitt Cancer Center</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Albert Einstein College of Medicine</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10461</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>September 13, 2012</study_first_submitted>
  <study_first_submitted_qc>September 27, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 2, 2012</study_first_posted>
  <last_update_submitted>September 22, 2020</last_update_submitted>
  <last_update_submitted_qc>September 22, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 24, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paclitaxel</mesh_term>
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Doxorubicin</mesh_term>
    <mesh_term>Liposomal doxorubicin</mesh_term>
    <mesh_term>Albumin-Bound Paclitaxel</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01697293
org study id: 2011-269
secondary id: NCI-2013-01311
secondary id: 11-051
secondary id: TCN-PM
secondary id: PTX-200-BC-1501.1
secondary id: PTX-200
secondary id: 007884
secondary id: 2011-269
secondary id: P30CA013330
secondary id: R01CA098473
nct id: NCT01697293
lead sponsor: 
collaborator: 
has dmc: Yes
This phase I/II trial studies the side effects and the best dose of triciribine phosphate
      when given together with paclitaxel, doxorubicin hydrochloride, and cyclophosphamide and to
      see how well they work in treating patients with stage IIB-IV breast cancer. Triciribine
      phosphate may stop the growth of tumor cells by blocking some of the enzymes needed for cell
      growth. Drugs used in chemotherapy, such as paclitaxel, doxorubicin hydrochloride, and
      cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing
      the cells, by stopping them from dividing, or by stopping them from spreading. Giving
      triciribine phosphate with paclitaxel, doxorubicin hydrochloride, and cyclophosphamide may be
      a better treatment for breast cancer.
PRIMARY OBJECTIVES:

      I. To determine the recommended phase II dose of PTX-200 (triciribine phosphate) given on
      days 1, 8, and 15 every 28 days (maximum of 9 doses) when combined with weekly paclitaxel (80
      mg/m^2) for 12 weeks in patients with metastatic breast cancer. (Phase I and Expansion
      Cohort) II. To determine the pathologic response rate (Residual Cancer Burden [RCB] score
      0-1) after sequential weekly paclitaxel plus PTX 200 weekly, 3 weeks out of 4, followed by
      doxorubicin (doxorubicin hydrochloride) (60 mg/m^2) and cyclophosphamide (600 mg/m^2) every 2
      weeks x 4 cycles in patients with clinical stage IIB-IIIC breast cancer. (Phase II).

      III. To determine the feasibility and safety of the combination of sequential weekly
      paclitaxel plus PTX-200 (days 1, 8, and 15) followed by doxorubicin/cyclophosphamide. (Phase
      II)

      SECONDARY OBJECTIVES:

      I. To correlate pre-treatment levels of erb-b2 receptor tyrosine kinase (ErbB)1, 2, 3, 4 and
      zinc finger protein 217 (ZNF217), and phosphorylated levels of v-akt murine thymoma viral
      oncogene homolog 1 (Akt), signal transducer and activator of transcription 3 (acute-phase
      response factor) (STAT3), extracellular signal-regulated protein kinases 1 and 2 (Erk1/2) to
      pathologic (RCB score 0-1) response (Sebti laboratory [lab]). (Phase I or II) II. To
      correlate the percent decrease in the levels of phosphorylated (phospho-)Akt (S473),
      phospho-S6 (S235-236), phospho-proline-rich Akt substrate, 40 kDa (PRAS40) (threonine
      [Thr]246), phosphatase and tensin homolog (PTEN), Stathmin, pyruvate dehydrogenase kinase,
      isozyme 1 (PDK1), cyclin D1, phospho-STAT3, ras homolog gene family, member C (Rho C), and
      phospho-Erk 1-2 with pathologic response rate (RCB score 0-1), percent inhibition of
      proliferation (Ki-67) and percent induction of apoptosis (terminal deoxynucleotidyl
      transferase dUTP nick end labeling [Tunel]) (Sebti lab). (Phase I or II)

      OUTLINE: This is a phase I, dose-escalation study of triciribine phosphate followed by an
      expansion cohort and a phase II study.

      COURSES A 1-12 (PHASE I & II): Patients receive triciribine phosphate intravenously (IV) over
      60 minutes on days 1, 8, and 15, 29, 36, 43, 57, 64, and 71 and paclitaxel IV over 1 hour on
      days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 79. Treatment repeats every week for 12
      courses in the absence of disease progression or unacceptable toxicity.

      COURSES B 1-4 (PHASE II): Patients receive doxorubicin hydrochloride IV over 5-10 minutes and
      cyclophosphamide IV over 30-60 minutes on day 1. Treatment repeats every 14 days for 4
      courses in the absence of disease progression or unacceptable toxicity.

      SURGERY (PHASE II): Eligible patients undergo modified radical mastectomy, radical
      mastectomy, segmental mastectomy or lumpectomy with an axillary lymph node dissection or
      biopsy.

      After completion of study treatment, patients with metastatic disease are followed up every 3
      months for 1 year and patients with locally advanced disease are followed up every 6 months
      for 2 years and then yearly for 3 years.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Pathologic response (RCB score 0-1), assessed using the criteria of Chevallier (Phase II)
time frame: At time of surgery
description: The estimated pCR along with exact confidence interval will be presented.
measure: Recommended phase II dose of triciribine phosphate, based on the incidence of dose-limiting toxicity graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (Phase I)
time frame: 28 days
description: Adverse effects will be summarized using frequency tables. The proportion of patients who completed all 12 courses of paclitaxel (at full dose or with dose modification) will be tabulated.
measure: Clinical complete response and partial response, based on tumor measurements obtained by physical exam
time frame: Up to 20 weeks (completion of courses B 1-4)
arm group label: Treatment (chemotherapy, surgery)
arm group type: Experimental
description: COURSES A 1-12 (PHASE I & II): Patients receive triciribine phosphate IV over 60 minutes on days 1, 8, and 15, 29, 36, 43, 57, 64, and 71 and paclitaxel IV over 1 hour on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 79. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity.
COURSES B 1-4 (PHASE II): Patients receive doxorubicin hydrochloride IV over 5-10 minutes and cyclophosphamide IV over 30-60 minutes on day 1. Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.
SURGERY (PHASE II): Eligible patients undergo modified radical mastectomy, radical mastectomy, segmental mastectomy or lumpectomy with an axillary lymph node dissection or biopsy.
intervention type: Drug
intervention name: Cyclophosphamide
description: Given IV
arm group label: Treatment (chemotherapy, surgery)
other name: (-)-Cyclophosphamide
other name: 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
other name: Carloxan
other name: Ciclofosfamida
other name: Ciclofosfamide
other name: Cicloxal
other name: Clafen
other name: Claphene
other name: CP monohydrate
other name: CTX
other name: CYCLO-cell
other name: Cycloblastin
other name: Cycloblastine
other name: Cyclophospham
other name: Cyclophosphamid monohydrate
other name: Cyclophosphamidum
other name: Cyclophosphan
other name: Cyclophosphane
other name: Cyclophosphanum
other name: Cyclostin
other name: Cyclostine
other name: Cytophosphan
other name: Cytophosphane
other name: Cytoxan
other name: Fosfaseron
other name: Genoxal
other name: Genuxal
other name: Ledoxina
other name: Mitoxan
other name: Neosar
other name: Revimmune
other name: Syklofosfamid
other name: WR- 138719
intervention type: Drug
intervention name: Doxorubicin Hydrochloride
description: Given IV
arm group label: Treatment (chemotherapy, surgery)
other name: 5,12-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)
other name: ADM
other name: Adriacin
other name: Adriamycin
other name: Adriamycin Hydrochloride
other name: Adriamycin PFS
other name: Adriamycin RDF
other name: ADRIAMYCIN, HYDROCHLORIDE
other name: Adriamycine
other name: Adriblastina
other name: Adriblastine
other name: Adrimedac
other name: Chloridrato de Doxorrubicina
other name: DOX
other name: DOXO-CELL
other name: Doxolem
other name: Doxorubicin.HCl
other name: Doxorubin
other name: Farmiblastina
other name: FI 106
other name: FI-106
other name: hydroxydaunorubicin
other name: Rubex
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Treatment (chemotherapy, surgery)
intervention type: Drug
intervention name: Paclitaxel
description: Given IV
arm group label: Treatment (chemotherapy, surgery)
other name: Anzatax
other name: Asotax
other name: Bristaxol
other name: Praxel
other name: Taxol
other name: Taxol Konzentrat
intervention type: Procedure
intervention name: Therapeutic Conventional Surgery
description: Undergo modified radical mastectomy, radical mastectomy, segmental mastectomy or lumpectomy with an axillary lymph node dissection or biopsy
arm group label: Treatment (chemotherapy, surgery)
intervention type: Drug
intervention name: Triciribine Phosphate
description: Given IV
arm group label: Treatment (chemotherapy, surgery)
other name: 1, 5-Dihydro-5-methyl-1-(5-O-phosphono-.beta.-D-ribofuranosyl)-1,4,5, 6,8-pentaazaacenaphthylen-3-amine
other name: 1,4, 5,6,8-Pentaazaacenaphthylen-3-amine, 1, 5-dihydro-5-methyl-1-(5-O-phosphono-.beta.-D-ribofuranosyl)- (9CI)
other name: 1,4,5,6, 8-Pentaazaacenaphthalen-3-amine, 1, 5-dihydro-5-methyl-1-(5-O-phosphono-.beta.-D-ribofuranosyl)-
other name: 3-Amino-1, 5-dihydro-5-methyl-1-.beta.-D-ribofuranosyl-1,4,5,6, 8-pentaazaacenaphthylene 5'-(dihydrogen phosphate)
other name: TCN
other name: Triciribine
other name: Tricycloside Phosphate
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Joseph Sparano
role: Principal Investigator
affiliation: Albert Einstein College of Medicine
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Paclitaxel
mesh term: Cyclophosphamide
mesh term: Doxorubicin
mesh term: Liposomal doxorubicin
mesh term: Albumin-Bound Paclitaxel