A Study of Triciribine Phosphate Monohydrate (TCN-PM)

Overview[ - collapse ][ - ]

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.
ConditionMetastatic Breast Cancer
Carcinoma Breast Stage IV
InterventionDrug: Triciribine
Drug: Paclitaxel
Drug: Doxorubicin
Drug: Cyclophosphamide
PhasePhase 1/Phase 2
SponsorJoseph Sparano
Responsible PartyAlbert Einstein College of Medicine of Yeshiva University
ClinicalTrials.gov IdentifierNCT01697293
First ReceivedSeptember 13, 2012
Last UpdatedSeptember 27, 2012
Last verifiedSeptember 2012

Tracking Information[ + expand ][ + ]

First Received DateSeptember 13, 2012
Last Updated DateSeptember 27, 2012
Start DateJanuary 2012
Estimated Primary Completion DateJune 2014
Current Primary Outcome MeasuresRecommended 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.
Current 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)

Descriptive Information[ + expand ][ + ]

Brief TitleA Study of Triciribine Phosphate Monohydrate (TCN-PM)
Official TitleA 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
Brief Summary
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.
Detailed DescriptionNot Provided
Study TypeInterventional
Study PhasePhase 1/Phase 2
Study DesignEndpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition
  • Metastatic Breast Cancer
  • Carcinoma Breast Stage IV
InterventionDrug: Triciribine
Triciribine (15, 25, or 35 mg/m2) on days 1, 8, 15 every 28 days
Other Names:
TCN-PMDrug: Paclitaxel
Paclitaxel 80 mg/m2 IV infusion over 1 hour weekly x 12 weeks
Other Names:
TaxolDrug: Doxorubicin
Doxorubicin 60 mg/m2 IV over 5-10 minutes. Only patients with locally advanced disease eligible for the phase II portion.
Other Names:
DOXORUBICIN HYDROCHLORIDEDrug: Cyclophosphamide
Cyclophosphamide 600 mg/m2 IV infusion over 30-60 minutes. Only patients with locally advanced disease eligible for the phase II portion.
Other Names:
Cytoxan
Study Arm (s)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)

Recruitment Information[ + expand ][ + ]

Recruitment StatusRecruiting
Estimated Enrollment46
Estimated Completion DateJune 2014
Estimated Primary Completion DateJanuary 2014
Eligibility 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
- 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.
GenderFemale
Ages18 Years
Accepts Healthy VolunteersNo
ContactsContact: Joseph Sparano, MD
718-904-2900
jsparano@montefiore.org
Location CountriesUnited States

Administrative Information[ + expand ][ + ]

NCT Number NCT01697293
Other Study ID Numbers2011-269
Has Data Monitoring CommitteeYes
Information Provided ByAlbert Einstein College of Medicine of Yeshiva University
Study SponsorJoseph Sparano
CollaboratorsCahaba Pharmaceuticals
Investigators Study Chair: Joseph Sparano, MD Montefiore Medical Center-Weiler DivisionPrincipal Investigator: Eleni Andreopoulou, MD Montefiore Medical Center-Weiler DivisionPrincipal Investigator: Christine Pellegrino, MD Montefiore Medical Center-Moses Division
Verification DateSeptember 2012

Locations[ + expand ][ + ]

Montefiore Medical Center -Department of Medical Oncology
Bronx, New York, United States, 10461
Contact: Joseph Sparano, MD | 718-904-2900 | jsparano@montefiore.org
Principal Investigator: Joseph Sparano, MD
Recruiting