PTX-200, Paclitaxel, Doxorubicin Hydrochloride, and Cyclophosphamide in Treating Patients With Stage IIB-IV Breast Cancer

NCT01697293 | Terminated Phase 1 DMC

• 9 other identifiers: 2011-269NCI-2013-0131111-051TCN-PMPTX-200-BC-1501.1PTX-200007884P30CA013330R01CA098473
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 2

Brief Summary

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.

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

Outcome Measures

Primary Outcomes (2)

• Pathologic response (RCB score 0-1), assessed using the criteria of Chevallier (Phase II)

  The estimated pCR along with exact confidence interval will be presented.

  At time of surgery

• 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)

  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.

  28 days

Secondary Outcomes (1)

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

  Up to 20 weeks (completion of courses B 1-4)

Study Arms (1)

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.

Drug: Cyclophosphamide; Drug: Doxorubicin Hydrochloride; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel; Procedure: Therapeutic Conventional Surgery; Drug: Triciribine Phosphate

Interventions

Cyclophosphamide DRUG

Given IV

Also known as: (-)-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, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (chemotherapy, surgery)

Doxorubicin Hydrochloride DRUG

Given IV

Also known as: 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.HCl, Doxorubin, Farmiblastina, FI 106, FI-106, hydroxydaunorubicin, Rubex

Treatment (chemotherapy, surgery)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (chemotherapy, surgery)

Paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Treatment (chemotherapy, surgery)

Therapeutic Conventional Surgery PROCEDURE

Undergo modified radical mastectomy, radical mastectomy, segmental mastectomy or lumpectomy with an axillary lymph node dissection or biopsy

Treatment (chemotherapy, surgery)

Triciribine Phosphate DRUG

Given IV

Also known as: 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, Tricycloside Phosphate

Treatment (chemotherapy, surgery)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Phase I and expansion cohort: Patients must have histologically or cytologically confirmed adenocarcinoma of the breast associated with clinical stage: IV (see American Joint Committee on Cancer \[AJCC\] staging criteria, 7th edition) or stage IIB-IIIC (expansion cohort only)
• 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, 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 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)/alanine aminotransferase (ALT) =\< 2.5 x institutional upper limit of normal
• Left ventricular ejection fraction (LVEF) within normal institutional limits
• Creatinine within normal institutional limits
• LVEF at or above institutional lower limits of normal (\>= 50%), or at least 5% above lower limits of normal if prior anthracycline exposure (by echocardiogram or nuclear scan within 12 weeks of registration)
• Electrocardiogram (ECG) corrected QT (QTC) \< 450 msec

You may not qualify if:

• Patients 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 (eg, 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
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with PTX-200; these potential risks may also apply to other agents used in this study
• Human immunodeficiency virus (HIV)-positive patients receiving combination antiretroviral therapy are excluded from the study

Sponsors & Collaborators

• Prescient Therapeutics, Ltd.: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Albert Einstein College of Medicine

The Bronx, New York, 10461, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Cyclophosphamide; Doxorubicin; Paclitaxel; Taxes; triciribine phosphate; triciribine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations

Study Officials

• Joseph Sparano

  Albert Einstein College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2012
• First Posted: October 2, 2012
• Study Start: January 1, 2012
• Primary Completion: June 1, 2020
• Study Completion: June 1, 2020
• Last Updated: September 24, 2020

Record last verified: 2020-09

Locations

US (2)