Clinical trial NCT01227408: Neoadjuvant Doxorubicin, Polyglutamate Paclitaxel, Capecitabine and Metronomic Chemotherapy in Breast Cancer
Official title: Phase II Clinical Trial of Neoadjuvant Weekly Doxorubicin, Polyglutamate Paclitaxel, Capecitabine and Metronomic Chemotherapy in Breast Cancer
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Breast Cancer
Keywords: Patients with confirmed breast cancer for neoadjuvant chemotherapy
Lead sponsor: University of Southern California
Sponsor class: OTHER
Collaborators: name: CTI BioPharma
First posted: 2010-10-25
Enrollment: 0
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Response
timeFrame: At surgical resection on about week 30
Secondary outcomes:
measure: Toxicity
timeFrame: Every 4 weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center
state: California
Study officials:
affiliation: University of Southern California
name: Agustin Garcia, MD
role: PRINCIPAL_INVESTIGATOR
References: