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Breast AdenocarcinomaPhase 1/2NCT01697293

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

A Phase 1/2 study testing Cyclophosphamide, Doxorubicin Hydrochloride and Laboratory Biomarker Analysis in people with Breast Adenocarcinoma and Estrogen Receptor Positive, run by Prescient Therapeutics, Ltd. at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cyclophosphamide, Doxorubicin Hydrochloride and Laboratory Biomarker Analysis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
34 participants
Where
2 sitesUnited States
Study dates
Jan 2012to Jun 2020
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 21Show fewer
  • 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
  • Serum calcium within normal institutional limits
  • Serum phosphorus within normal institutional limits
  • Fasting glucose within normal limits
  • 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 (for phase II only); patients 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 (and no prior adjuvant chemotherapy for previous breast malignancy)
  • Women of childbearing 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; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • 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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Moffitt Cancer Center

    Tampa, Florida, 33612

  • Albert Einstein College of Medicine

    The Bronx, New York, 10461

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • Doxorubicin HydrochlorideDrug

    Also called 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

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • PaclitaxelDrug

    Also called Anzatax, Asotax, Bristaxol, Praxel

    Given IV

  • Therapeutic Conventional SurgeryProcedure or surgery

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

  • Triciribine PhosphateDrug

    Also called 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)

    Given IV

Study groups in NCT01697293
Study groupRoleWhat they receive
Treatment (chemotherapy, surgery)ExperimentalCOURSES 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.
Receives: Drug: Cyclophosphamide; Drug: Doxorubicin Hydrochloride; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel; Procedure: Therapeutic Conventional Surgery; Drug: Triciribine Phosphate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: At time of surgery

  2. 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.

    Measured: 28 days

Secondary outcomes (1)

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

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Oct 2012 (estimated)
  2. Study startJan 2012
  3. Primary completionJun 2020
  4. Study completionJun 2020

Why it stopped: criteria for continuing enrollment in Phase 2 portion was not met

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
34 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01697293
Sponsor's protocol ID
2011-269
Other IDs
NCI-2013-01311, 11-051, TCN-PM, PTX-200-BC-1501.1, PTX-200, 007884, 2011-269, P30CA013330
Status last verified
Sep 2020
First submitted
13 Sep 2012
Last updated
24 Sep 2020
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Cyclophosphamide, Doxorubicin Hydrochloride and Laboratory Biomarker Analysis in people with Breast Adenocarcinoma and Estrogen Receptor Positive, run by Prescient Therapeutics, Ltd. at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 24 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: criteria for continuing enrollment in Phase 2 portion was not met). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pathologic response (RCB score 0-1), assessed using the criteria of Chevallier (Phase II) (time frame: At time of surgery). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01697293.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2020.

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