Clinical Trials /

Triciribine Phosphate, Paclitaxel, Doxorubicin Hydrochloride, and Cyclophosphamide in Treating Patients With Stage IIB-IV Breast Cancer

NCT01697293

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Triciribine Phosphate</span>, <span class="go-doc-concept go-doc-intervention">Paclitaxel,</span> <span class="go-doc-concept go-doc-intervention">Doxorubicin Hydrochloride</span>, and <span class="go-doc-concept go-doc-intervention">Cyclophosphamide</span> in Treating Patients With Stage IIB-IV <span class="go-doc-concept go-doc-disease">Breast Cancer</span>

Title

  • Brief Title: Triciribine Phosphate, Paclitaxel, Doxorubicin Hydrochloride, and Cyclophosphamide in Treating Patients With Stage IIB-IV Breast Cancer
  • Official Title: A Phase I-II Study of Triciribine Phosphate Monohydrate (TCN-PM) Plus Sequential Weekly Paclitaxel Followed by Dose-Dense Doxorubicin and Cyclophosphamide in Patients With Metastatic and Locally Advanced Breast Cancer
  • Clinical Trial IDs

    NCT ID: NCT01697293

    ORG ID: 2011-269

    NCI ID: NCI-2013-01311

    Trial Conditions

    Breast Adenocarcinoma

    Estrogen Receptor Positive

    HER2/Neu Negative

    Recurrent Breast Carcinoma

    Stage IIB Breast Cancer

    Stage IIIA Breast Cancer

    Stage IIIB Breast Cancer

    Stage IIIC Breast Cancer

    Stage IV Breast Cancer

    Trial Interventions

    Drug Synonyms Arms
    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, CYCLOPHOSPHAMIDE, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719 Treatment (chemotherapy, surgery)
    Doxorubicin Hydrochloride 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), ADM, Adriacin, Adriamycin, Adriamycin Hydrochloride, Adriamycin PFS, Adriamycin RDF, ADRIAMYCIN, HYDROCHLORIDE, Adriamycine, Adriblastina, Adriblastine, Adrimedac, Chloridrato de Doxorrubicina, DOX, DOXO-CELL, Doxolem, DOXORUBICIN HYDROCHLORIDE, Doxorubicin.HCl, Doxorubin, Farmiblastina, FI 106, FI-106, hydroxydaunorubicin, Rubex Treatment (chemotherapy, surgery)
    Paclitaxel Anzatax, Asotax, Bristaxol, PACLITAXEL, Praxel, Taxol, Taxol Konzentrat Treatment (chemotherapy, surgery)
    Triciribine Phosphate 1, 5-Dihydro-5-methyl-1-(5-O-phosphono-.beta.-D-ribofuranosyl)-1,4,5, 6,8-pentaazaacenaphthylen-3-amine, 1,4, 5,6,8-Pentaazaacenaphthylen-3-amine, 1, 5-dihydro-5-methyl-1-(5-O-phosphono-.beta.-D-ribofuranosyl)- (9CI), 1,4,5,6, 8-Pentaazaacenaphthalen-3-amine, 1, 5-dihydro-5-methyl-1-(5-O-phosphono-.beta.-D-ribofuranosyl)-, 3-Amino-1, 5-dihydro-5-methyl-1-.beta.-D-ribofuranosyl-1,4,5,6, 8-pentaazaacenaphthylene 5'-(dihydrogen phosphate), TCN, Triciribine, TRICIRIBINE PHOSPHATE, Tricycloside Phosphate Treatment (chemotherapy, surgery)

    Trial Purpose

    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.

    Detailed Description

    PRIMARY OBJECTIVES:

    I. To determine the recommended phase II dose of triciribine (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.

    II. To determine the pathologic complete response rate (including breast and breast plus
    axillary nodes) after sequential weekly paclitaxel triciribine 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
    triciribine, followed by doxorubicin/cyclophosphamide. (Phase II)

    SECONDARY OBJECTIVES:

    I. To correlate pre-treatment levels of epidermal growth factor receptor, avian
    erythroblastic leukemia viral (v-erb-b) oncogene homolog1, 2, 3, 4 (ErbB1,2,3,4), and
    phosphorylated levels of protein kinase B (Akt), signal transducer and activator of
    transcription 3 (STAT3), extracellular signal-regulated kinase (Erk)1/2 to clinical response
    (Sebti 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 clinical response rates,
    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 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.

    Trial Arms

    Name Type Description Interventions
    Treatment (chemotherapy, surgery) Experimental 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. Cyclophosphamide, Doxorubicin Hydrochloride, Paclitaxel, Triciribine Phosphate

    Eligibility Criteria

    Inclusion Criteria:

    - Phase I: Patients must have histologically or cytologically confirmed adenocarcinoma
    of the breast associated with the following clinical stage: clinical IV (see American
    Joint Committee on Cancer [AJCC] staging criteria, 7th Edition)

    - Phase II: Patients must have histologically or cytologically confirmed adenocarcinoma
    of the breast associated with the following clinical stage: IIB, IIIA, IIIB, or IIIC
    (see AJCC staging criteria, 7th Edition); the tumor must be human epidermal growth
    factor receptor 2 (Her2)/neu negative (by DAKO Herceptest, fluorescent in situ
    hybridization [FISH], or other approved assay)

    - Phase I: Up to two prior non-taxane chemotherapy regimens for metastatic disease is
    permitted for patients enrolled on the phase I portion of the trial; patients with
    HER2/neu positive breast cancer are not eligible; patients treated with prior
    anthracycline therapy as neoadjuvant, adjuvant, or metastatic therapy are not
    eligible; patients with estrogen receptor (ER)-positive disease are required to have
    relapse or progression on at least one line of endocrine therapy

    - Phase II: No prior chemotherapy, irradiation, or definitive therapeutic surgery
    (e.g., mastectomy or lumpectomy or axillary dissection) for this malignancy; patients
    who have had a prior sentinel lymph node biopsy for this malignancy are eligible

    - Patients who received tamoxifen or another selective estrogen receptor modulator
    (SERM) for prevention or treatment of breast cancer or for other indications (e.g.,
    osteoporosis, prior ductal carcinoma in situ [DCIS]), or who receive aromatase
    inhibitors for prevention or treatment of breast cancer, are eligible; patients who
    are hormone-receptor positive and who have received other hormonal agents for the
    treatment of breast cancer (e.g., Fulvestrant) are also eligible; tamoxifen therapy
    or other hormonal agents should be discontinued at least 1 week before the patient is
    enrolled on this study

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

    - Leukocytes >= 3,000/uL

    - Absolute neutrophil count >= 1,500/uL

    - Platelets >= 100,000/uL

    - Total bilirubin within normal institutional limits

    - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
    [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
    =< 2.5 x institutional upper limit of normal

    - Left ventricular ejection fraction within normal institutional limits

    - Creatinine within normal institutional limits

    - Left ventricular ejection fraction at or above institutional lower limits of normal
    (by echocardiogram or nuclear scan within 12 weeks of registration)

    - Electrocardiogram (EKG) corrected QT (QTC) < 450 msec

    - Serum calcium within normal institutional limits

    - Serum phosphorus within normal institutional limits

    - Fasting glucose within normal limits

    - Patients must be disease-free of prior invasive malignancies for >= 2 years with the
    exception of curatively-treated basal cell or squamous cell carcinoma of the skin,
    carcinoma in situ of the cervix (for phase II only); patient with the following prior
    or concurrent diagnoses are eligible: lobular carcinoma in situ, contralateral ductal
    carcinoma in situ, or contralateral invasive ductal and/or lobular cancer (an no
    prior adjuvant chemotherapy for previous breast malignancy)

    - Women of child-bearing potential must agree to use adequate contraception (hormonal
    or barrier method of birth control) prior to study entry and for the duration of
    study participation; should a woman become pregnant or suspect she is pregnant while
    participating in this study, she should inform her treating physician immediately

    - Ability to understand and the willingness to sign a written informed consent document

    Exclusion Criteria:

    - Patients may not be receiving any other investigational agents

    - History of allergic reactions attributed to compounds of similar chemical or biologic
    composition to triciribine or other agents used in the study (e.g., imidazoles,
    quinolones)

    - Uncontrolled intercurrent illness including, but not limited to, ongoing or active
    infection, diabetes mellitus requiring therapy (insulin or oral hypoglycemic agents),
    congenital prolonged QT syndrome, requirement for a drug known to prolong the QT
    interval, a history of QT prolongation, a screening QTc >= 450 msec,
    hypertriglyceridemia requiring therapy, symptomatic congestive heart failure,
    unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social
    situations that would limit compliance with study requirements

    - Pregnant women are excluded from this study; breastfeeding should be discontinued if
    the mother is treated with triciribine; these potential risks may also apply to other
    agents used in this study

    - Human immunodeficiency virus (HIV)-positive patients receiving combination
    anti-retroviral therapy are excluded from the study

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Pathologic complete response (pCR), assessed using the criteria of Chevallier (Phase II)

    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)

    Secondary Outcome Measures

    Clinical complete response and partial response, based on tumor measurements obtained by physical exam

    Trial Keywords