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Clinical Trial 16664

Cancer Type: Breast
Interventions:Adriamycin (doxorubicin); Taxol (paclitaxel); Triciribine (TCN-PM (0002)); cyclophosphamide; cytoxan (cyclophosphamide); doxorubicin; paclitaxel

Study Type: Treatment
Phase of Study: Phase I/II

  • Heather Han

Call 813-745-6100
or 1-800-679-0775

Study 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


The purpose of the trial is to determine the appropriate dose of PTX-200 to use in combination with paclitaxel in patients with metastatic breast cancer and other cancers, and whether it enhances the effectiveness of chemotherapy in patients with locally advanced breast cancer treated with chemotherapy prior to surgery.


Primary Objectives: To determine the recommended phase II dose of triciribine 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 portion of trial) To determine the pathologic complete response rate (including breast and breast plus axillary nodes) after sequential weekly paclitaxel triciribine followed by doxorubicin (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 portion). To determine the feasibility and safety of the combination of sequential weekly paclitaxel plus triciribine, followed by doxorubicin/cyclophosphamide (phase II portion) Secondary Objectives: Laboratory objectives: To correlate pre-treatment levels of ErbB1,2,3,4, and phosphorylated levels of Akt, STAT3, Erk1/2 to clinical response (Sebti lab - phase I or II portion). To correlate the percent decrease in the levels of phospho-Akt(S473), phospho-S6 (S235-236), phospho-PRAS40 (Thr246), PTEN, Stathmin, PDK1, Cyclin D1, phospho-STAT3, Rho C, and phospho-Erk 1-2 with clinical response rates, percent inhibition of proliferation (Ki-67) and percent induction of apoptosis (Tunel) (Sebti lab - phase I or II portion).

Inclusion Criteria

  • PHASE I AND EXPANSION COHORT: Participants must have histologically or confirmed adenocarcinoma of the breast associated with clinical stage IV (see AJCC staging criteria, 7th edition) or stage IIB-IIIC expansion cohort only).
  • PHASE II: Participants must have histologically or 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 HER2/neu negative (by Dako Herceptest, fluorescence based in situ hybridization (FISH), or other approved assay).
  • PHASE I AND EXPANSION COHORT: Up to two prior non-taxane chemotherapy regimens for metastatic disease are 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 unless the following conditions are met: (a) prior cumulative doxorubicin dose is . 240 mg/m^2 (or epirubicin dose is . 400 mg/m^2), and (b) left ventricular ejection fraction (LVEF) obtained at baseline is at least 50% (or, . 5% above lower institutional limits of normal whichever is higher). Patients with 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.
  • Age ≥ 18 years
  • ECOG performance status 0 or 1.
  • Must have normal organ and marrow function as defined in the protocol within 2 weeks of registration.
  • 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). Patients 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 (and no prior adjuvant chemotherapy for previous breast malignancy).
  • women of childbearing 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.
  • Ability to understand and the willingness to sign a written informed consent document.

  • Exclusion Criteria

  • Potential participants may not be receiving any other investigational agents during protocol therapy, or up to 30 days prior to beginning protocol therapy. There should be a least a 1-week interval between last dose of endocrine therapy and protocol therapy, and at least 3 weeks for the last dose of biologic therapy (e.g., bevacizumab) or cytotoxic therapy (or 2 weeks for capecitabine or weekly paclitaxel, 6 weeks for mitomycin-C and nitrosoureas), and adequately recovered from adverse effects from prior therapy to meet all other eligibility criteria.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to PTX-200 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. Patients with chronic interstitial or inflammatory lung disease, active liver disease (acute or chronic, excluding cancer-related liver involvement/metastases) are not eligible.
  • Women who are pregnant or nursing.
  • Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, HIV-positive patients receiving combination antiretroviral therapy are excluded from the study because of possible pharmacokinetic interactions with PTX-200 or other agents administered during the study.