A Study of Triciribine Phosphate Monohydrate (TCN-PM)

This study is currently recruiting participants.
Verified September 2012 by Albert Einstein College of Medicine of Yeshiva University
Sponsor:
Collaborator:
Cahaba Pharmaceuticals
Information provided by (Responsible Party):
Joseph Sparano, Albert Einstein College of Medicine of Yeshiva University
ClinicalTrials.gov Identifier:
NCT01697293
First received: September 13, 2012
Last updated: September 27, 2012
Last verified: September 2012
  Purpose

The investigators hypothesize that the addition of a specific AKT inhibitor (triciribine) to the regimen of weekly paclitaxel (followed sequentially by AC) will enhance the pathologic complete response rate in patients with locally advanced breast cancer.


Condition Intervention Phase
Metastatic Breast Cancer
Carcinoma Breast Stage IV
Drug: Triciribine
Drug: Paclitaxel
Drug: Doxorubicin
Drug: Cyclophosphamide
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Albert Einstein College of Medicine of Yeshiva University:

Primary Outcome Measures:
  • Recommended phase II dose of triciribine plus weekly paclitaxel. [ Time Frame: Up to 12 weeks after registration and completion of weekly paclitaxel ] [ Designated as safety issue: Yes ]
    To determine the recommended phase II dose of triciribine used in combination with weekly paclitaxel.


Secondary Outcome Measures:
  • Pathologic complete response rate (pCR rate) [ Time Frame: After completion of sequential paclitaxel plus triciribine followed by doxorubicin-cyclophopshamide (up to approximately 24 weeks after registration) ] [ Designated as safety issue: No ]
    To determine the pathologic complete response rate (including breast and breast plus axillary nodes) after sequential weekly paclitaxel triciribine followed by doxorubicin and cyclophosphamide in patients with clinical stage IIB-IIIC breast cancer (phase II).

  • Number of Participants with Adverse Events as a Measure of Feasibility and Safety [ Time Frame: each day of the 12 and/or 20 treatment days ] [ Designated as safety issue: Yes ]
    Evaluate safety and feasibility of the combination of sequential weekly paclitaxel plus triciribine, followed by doxorubicin/cyclophosphamide (phase II portion)


Estimated Enrollment: 46
Study Start Date: January 2012
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
  • Cycles A 1-12: Triciribine + Paclitaxel (Phase I and II portion of study)
  • Cycles B 1-4: Doxorubicin/Cyclophosphamide (Phase II portion of study only)
Drug: Triciribine
Triciribine (15, 25, or 35 mg/m2) on days 1, 8, 15 every 28 days
Other Name: TCN-PM
Drug: Paclitaxel
Paclitaxel 80 mg/m2 IV infusion over 1 hour weekly x 12 weeks
Other Name: Taxol
Drug: Doxorubicin
Doxorubicin 60 mg/m2 IV over 5-10 minutes. Only patients with locally advanced disease eligible for the phase II portion.
Other Name: DOXORUBICIN HYDROCHLORIDE
Drug: Cyclophosphamide
Cyclophosphamide 600 mg/m2 IV infusion over 30-60 minutes. Only patients with locally advanced disease eligible for the phase II portion.
Other Name: Cytoxan

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Phase I: Patients must have histologically or cytologically confirmed adenocarcinoma of the breast associated with the following clinical stage: clinical IIIC or IV .The tumor must be Her2/neu negative
  • Phase II: Patients must have histologically or cytologically confirmed adenocarcinoma of the breast associated with the following clinical stage: IIB, IIIA, IIIB, or IIIC.The tumor must be Her2/neu negative
  • Phase I: Up to two prior non-taxane chemotherapy regimens for metastatic disease is permitted for patients enrolled on the phase I portion.
  • Phase II: No prior chemotherapy, irradiation, or definitive therapeutic surgery 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 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 (eg, Fulvestrant) are also eligible.
  • Age >18 years.
  • ECOG performance status 0 or 1.
  • Patients must have normal organ and marrow function as defined below within 2 weeks of registration (except where specified otherwise):
  • leukocytes >3,000/μl
  • absolute neutrophil count >1,500/μl
  • platelets >100,000/μl
  • total bilirubin within normal institutional limits
  • AST(SGOT)/ALT(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 for patients treated in the phase II portion of the trial who will receive AC chemotherapy)
  • EKG QTc < 450 msec
  • serum calcium & phosphorus within normal institutional limits
  • Hemoglobin A1C </= 6.5 %
  • 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. 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 due to the unknown effects.
  • 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
  • HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with triciribine or other agents administered during the study.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01697293

Contacts
Contact: Joseph Sparano, MD 718-904-2900 jsparano@montefiore.org
Contact: Shakira Forde, CCRP 718-904-2534 sforde@montefiore.org

Locations
United States, New York
Montefiore Medical Center -Department of Medical Oncology Recruiting
Bronx, New York, United States, 10461
Contact: Joseph Sparano, MD    718-904-2900    jsparano@montefiore.org   
Contact: Shakira Forde, CCRP    718-904-2534    sforde@montefiore.org   
Principal Investigator: Joseph Sparano, MD         
Sponsors and Collaborators
Joseph Sparano
Cahaba Pharmaceuticals
Investigators
Study Chair: Joseph Sparano, MD Montefiore Medical Center-Weiler Division
Principal Investigator: Eleni Andreopoulou, MD Montefiore Medical Center-Weiler Division
Principal Investigator: Christine Pellegrino, MD Montefiore Medical Center-Moses Division
  More Information

No publications provided

Responsible Party: Joseph Sparano, Associate Director for Cancer Clinical Research, Albert Einstein College of Medicine of Yeshiva University
ClinicalTrials.gov Identifier: NCT01697293     History of Changes
Other Study ID Numbers: 2011-269
Study First Received: September 13, 2012
Last Updated: September 27, 2012
Health Authority: United States: Food and Drug Administration
United States: Data and Safety Monitoring Board
United States: Institutional Review Board

Keywords provided by Albert Einstein College of Medicine of Yeshiva University:
Breast
Breast Cancer
Metastatic Breast Cancer
Advanced Breast Cancer
Carcinoma Breast Stage IV
Carcinoma Breast Stage IIIB
TCN-PM
Triciribine
Breast Diseases
Paclitaxel
Doxorubicin
Cyclophosphamide
Triciribine Phosphate Monohydrate

Additional relevant MeSH terms:
Breast Neoplasms
Carcinoma
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Cyclophosphamide
Doxorubicin
Paclitaxel
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on April 17, 2014