Ignite Creation Date:
2025-12-25 @ 1:24 AM
Ignite Modification Date:
2025-12-27 @ 11:35 PM
Study NCT ID:
NCT01697293
Status:
TERMINATED
Last Update Posted:
2020-09-24
First Post:
2012-09-13
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
PTX-200, Paclitaxel, Doxorubicin Hydrochloride, and Cyclophosphamide in Treating Patients With Stage IIB-IV Breast Cancer
Sponsor:
Prescient Therapeutics, Ltd.
Organization:
Study Overview
Official 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
Status:
TERMINATED
Status Verified Date:
2020-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
criteria for continuing enrollment in Phase 2 portion was not met
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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.
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.
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.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2013-01311 | REGISTRY | CTRP (Clinical Trial Reporting Program) | View | |
| 11-051 | None | None | View | |
| TCN-PM | None | None | View | |
| PTX-200-BC-1501.1 | None | None | View | |
| PTX-200 | None | None | View | |
| 007884 | None | None | View | |
| 2011-269 | OTHER | Albert Einstein College of Medicine | View | |
| P30CA013330 | NIH | None | https://reporter.nih.gov/quic… | View |
| R01CA098473 | NIH | None | https://reporter.nih.gov/quic… | View |