NCT01697293

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

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

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 34 (actual)
• Sponsor: Prescient Therapeutics, Ltd. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

PRIMARY OBJECTIVES: I. To determine the recommended phase II dose of PTX-200 (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. (Phase I and Expansion Cohort) II. To determine the pathologic response rate (Residual Cancer Burden \[RCB\] score 0-1) after sequential weekly paclitaxel plus PTX 200 weekly, 3 weeks out of 4, 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 PTX-200 (days 1, 8, and 15) followed by doxorubicin/cyclophosphamide. (Phase II) SECONDARY OBJECTIVES: I. To correlate pre-treatment levels of erb-b2 receptor tyrosine kinase (ErbB)1, 2, 3, 4 and zinc finger protein 217 (ZNF217), and phosphorylated levels of v-akt murine thymoma viral oncogene homolog 1 (Akt), signal transducer and activator of transcription 3 (acute-phase response factor) (STAT3), extracellular signal-regulated protein kinases 1 and 2 (Erk1/2) to pathologic (RCB score 0-1) response (Sebti laboratory \[lab\]). (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 pathologic response rate (RCB score 0-1), 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 an expansion cohort and 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.

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

Interventions

Type	Name	Description
DRUG	Cyclophosphamide	Given IV
DRUG	Doxorubicin Hydrochloride	Given IV
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	Paclitaxel	Given IV
PROCEDURE	Therapeutic Conventional Surgery	Undergo modified radical mastectomy, radical mastectomy, segmental mastectomy or lumpectomy with an axillary lymph node dissection or biopsy
DRUG	Triciribine Phosphate	Given IV

Timeline

• Start date: 2012-01-01
• Primary completion: 2020-06-01
• Completion: 2020-06-01
• First posted: 2012-10-02
• Last updated: 2020-09-24

Locations

2 sites across 1 country: United States