Neoadjuvant Doxorubicin, Polyglutamate Paclitaxel, Capecitabine and Metronomic Chemotherapy in Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01227408
Recruitment Status : Withdrawn (Sponsor withdrew due to funding issues)
First Posted : October 25, 2010
Last Update Posted : May 2, 2017
CTI BioPharma
Information provided by (Responsible Party):
University of Southern California

Brief Summary:

The investigators propose to conduct a clinical trial of neoadjuvant treatment utilizing chemotherapy formulations with favorable toxicity profiles: weekly doxorubicin, PPX and capecitabine. It is expected this combination will at least maintain the efficacy of a traditional chemotherapy regimen but will be associated with less toxicity, particularly nausea, vomiting and alopecia. In order to accomplish this the investigators have designed a chemotherapy regimen whose components (or administration schedule) are associated with minimal or no alopecia and are also considered to have low emetogenic potential.

In an attempt to improve the efficacy of the regimen the investigators plan to study an alternate schedule of cyclophosphamide and methotrexate administration (metronomic chemotherapy) which appears to inhibit angiogenesis and therefore enhance the activity of conventional cytotoxic chemotherapy administered concurrently.

In this trial the investigators aim to determine the clinical and pathologic response rate of 12 weeks of doxorubicin followed by 4 cycles of PPX and capecitabine. Metronomic chemotherapy with cyclophosphamide and methotrexate will be administered during the 24 weeks of chemotherapy.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: doxorubicin, paclitaxel poliglumex, capecitabine, cyclophosphamide, methotrexate Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Clinical Trial of Neoadjuvant Weekly Doxorubicin, Polyglutamate Paclitaxel, Capecitabine and Metronomic Chemotherapy in Breast Cancer
Estimated Study Start Date : February 2009
Estimated Primary Completion Date : February 2010
Estimated Study Completion Date : February 2011

Arm Intervention/treatment
Experimental: Metronomic Chemotherapy
Doxorubicin will be administered as an intravenous bolus, careful intravenous injection. PPX will be administerd as an intravenous 10 mins. infusion. Capecitabine and methotrexate will be taken orally twice a day. Cyclophosphamide will be taken orally once a day.
Drug: doxorubicin, paclitaxel poliglumex, capecitabine, cyclophosphamide, methotrexate
doxorubicin 20mg/m2 weekly x 12 wks, cyclophosphamide 50 mg PO qd x 12 wks, methotrexate 2.5 mg PO bid d1,2 wkly x 12. One week later paclitaxel poliglumex 135mg/m2 IV every 3 wks plus capecitabine 825 mg/m2 PO bid x 14days x 4 cycles

Primary Outcome Measures :
  1. Response [ Time Frame: At surgical resection on about week 30 ]

Secondary Outcome Measures :
  1. Toxicity [ Time Frame: Every 4 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • SWOG performance status of 0-2
  • Projected life expectancy of at least 3 months
  • Female age 18 years and over
  • Provision of informed consent prior to any study-related procedures.
  • Hormone receptor positive or negative tumor
  • Her 2 neu negative tumor
  • Negative pregnancy test for women of childbearing potential
  • Patients must agree to use some form of contraception while on this study at initiation and for the duration of participation in the study. Sexually active males must also use a reliable and appropriate method of contraception. Post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.
  • ANC > 1500, Platelet count > 100,000, Hemoglobin > 9.0
  • Serum creatinine < 1.5 mg/dl
  • Hepatic function: Patients must have adequate liver functions: AST or ALT < 2.5 X upper limit of normal (ULN), alkaline phosphatase < 2.5 X upper limit of normal. Serum Bilirubin < 1.5 mg
  • Peripheral neuropathy grade 0-1
  • No other concomitant therapy directed at the cancer is allowed.

Exclusion Criteria:

  • Serum bilirubin > 1.5 the upper limit of reference range (ULRR)
  • Serum creatinine >1.5
  • Prior therapy for this tumor.
  • Clinical Congestive Heart Failure
  • Women who are currently pregnant or breast feeding.
  • Receipt of any investigational agents within 30 days prior to commencing study treatment
  • Prior radiation must not have included ≥ 30% of major bone marrow containing areas (pelvis, lumbar spine)
  • No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, lobular carcinoma in-situ of the breast (LCIS), or any other cancer from which the patient has been disease-free for 5 years. Patients with prior invasive breast cancer or ductal carcinoma in-situ (DCIS) are eligible if they have been disease free for 5 years and did not receive prior treatment with doxorubicin and/or a taxane.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01227408

United States, California
USC/Norris Comprehensive Cancer Center
Los Angeles, California, United States, 90033
Sponsors and Collaborators
University of Southern California
CTI BioPharma
Principal Investigator: Agustin Garcia, MD University of Southern California

Responsible Party: University of Southern California Identifier: NCT01227408     History of Changes
Other Study ID Numbers: 1B-08-7
First Posted: October 25, 2010    Key Record Dates
Last Update Posted: May 2, 2017
Last Verified: April 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Southern California:
Patients with confirmed breast cancer for neoadjuvant chemotherapy

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Liposomal doxorubicin
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors