Therapy for Locally Advanced Breast Cancer Using Doxil, Paclitaxel, and Cyclophosphamide With Avastin

NCT00635050 | Completed Phase 2 Results DMC

• 2 other identifiers: F070824009UAB 0493
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the rate of pathological complete response (pCR) to the sequential therapy of Doxil, paclitaxel, and cyclophosphamide with concurrent Avastin for patients with locally advanced invasive (T2,T3, Nany, M0) breast carcinoma. Also, the study will evaluate the clinical and subclinical cardiotoxic effect(s) of this regimen, assess how feasible and safe the study is. Survival without any progression of disease will also be calculated. A regimen of chemotherapy will be given to replicate the high rate of pCR seen with conventional chemotherapy in patients with locally advanced breast cancer. Doxil will substitute the normally given doxorubicin. It is expected that the low effect or minimal effect of Doxil on cardiac function will minimize any additional risk of cardiotoxicity from Avastin. It is expected that clinical and subclinical rates of cardiotoxicity will be very low at the total doses to be given in this clinical trial.

Conditions

Invasive Breast Cancer

Keywords

Breast cancer

Outcome Measures

Primary Outcomes (1)

• Rate of Achievement of Pathological Complete Response (pCR)

  Results of the pathologic evaluation of the surgical specimen(s) from operation (segmental or total mastectomy) will be used to report the overall complete pathological response rate. Criteria used were those described by Kaufmann et al, Journal of Clinical Oncology 2003; 21(13):2600-2608. The definition of pCR used from this source was absence of invasive cancer in both resected breast tissue and in resected axillary nodes.

  After completion of at least 8 of the 9 chemotherapy doses and operation.

Secondary Outcomes (3)

• Number of Participant With Clinical or Subclinical Cardiotoxicity

  Prior to treatment and at completion of chemotherapy

• Calculate Progression Free Survival

  5 years

• Assess Toxicities of Regimen Including Hand Foot Syndrome

  Baseline, every 2 weeks during treatment, and at completion of therapy. Every 3 weeks during postoperative Avastin

Study Arms (1)

Doxil, Paclitaxel, Cyclophosphamide + Avastin

EXPERIMENTAL

Two stage phase II single arm trial to evaluate the pathologic complete response rate to sequential dose dense chemotherapy using Doxil 25 mg/M2 iv and Avastin 10 mg/kg iv every 2 weeks x 3, then paclitaxel 175 mg/M2 iv and Avastin 10 mg/kg iv every 2 weeks x 3, then cyclophosphamide 600 mg/M2 iv and Avastin 10 mg/kg iv every 2 weeks x 3, in patients with locally advanced invasive breast cancer.

Drug: Doxil, Paclitaxel, Cyclophosphamide, Avastin

Interventions

Doxil, Paclitaxel, Cyclophosphamide, Avastin DRUG

Regimen A: Doxil 25 mg/M2 iv and Avastin 10 mg/kg iv every 2 weeks x 3, then paclitaxel 175 mg/M2 i.v. and Avastin 10 mg/kg iv every 2 weeks x 3, then cyclophosphamide 600 mg/M2 i.v. and Avastin 10 mg/kg iv every 2 weeks x 3 . Patients who experience \<pCR to primary chemotherapy will receive an additional year of Avastin 15 mg/kg iv every 3 weeks, beginning 6-8 weeks after operation. Regimen B: Doxil 30 mg/M2 iv and Avastin 10 mg/kg iv every 2 weeks x 3, then paclitaxel 175 mg/M2 i.v. and Avastin 10 mg/kg iv every 2 weeks x 3, then cyclophosphamide 600 mg/M2 i.v. and Avastin 10 mg/kg iv every 2 weeks x 3. Patients who experience \<pCR to primary chemotherapy will receive an additional year of Avastin15 mg/kg iv every 3 weeks, beginning 6-8 weeks after operation.

Also known as: Bevacizumab (Avastin)

Doxil, Paclitaxel, Cyclophosphamide + Avastin

Eligibility Criteria

• Age: 19 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed, measurable, invasive breast carcinoma T \>2cm, Nany, M0.
• Patients with node-negative, ER or PR-positive tumors ≤4 cm in size whose tumors are low risk (defined as a score of 0-17) on an Oncotype DX profile are not eligible.
• years of age or greater
• Known ER, PR and HER-2 status (FISH assay to be done on specimens with 2+ or 3+ immunohistochemical staining for HER-2): patients with gene amplification on FISH study will be considered to be HER-2 positive. Patients for this study must be FISH negative if immunohistochemical stain is 2+ or 3+ positive; patients with negative, 0 or 1+ immunohistochemical stain for HER-2 are eligible.
• Known axillary nodal status: aspiration cytology or biopsy
• Documented menopausal status premenopausal (having menstrual periods or FSH \<35) or postmenopausal (≥12 months since last menstrual period with intact uterus and at least one ovary or FSH ≥35 or previous bilateral oophorectomy
• Non-pregnant if premenopausal (negative serum or urine pregnancy test within 7 days of starting chemotherapy) and not breast feeding
• Patients with reproductive potential must use an adequate contraceptive method (e.g., abstinence, intrauterine device, barrier device with spermicide or surgical sterilization) during treatment and for three months after completing treatment.
• Life expectancy of less than 12 weeks
• Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored Avastin cancer study
• Pregnant or lactating women.
• History of cardiac disease, with New York Heart Association Grade II or greater or clinical evidence of congestive heart failure.
• Serious comorbid medical conditions which would impair the ability to receive chemotherapy on time
• Previous invasive cancer within the last 5 years
• Altered mental status or dementia which would interfere with understanding of informed consent and ability to comply with study and follow-up procedures.

You may not qualify if:

• Minor surgical procedure (excluding placement of a vascular access device) such as fine needle aspiration or core needle biopsy within 7 days of beginning therapy
• Urine protein:creatinine ratio ≥1.0 at initial screening
• Known hypersensitivity to any component of Avastin
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months of beginning therapy
• Serious, non-healing wound, active ulcer, or untreated bone fracture
• Any prior history of hypertensive crisis or hypertensive encephalopathy
• Known CNS metastasis, except for treated brain metastasis. Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. Anticonvulsants (stable dose) are allowed. Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, LINAC, or equivalent) or a combination as deemed appropriate by the treating physician. Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to Day 1 will be excluded.

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• Ortho Biotech, Inc.: collaborator
• Genentech, Inc.: collaborator

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294 - 0104, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

liposomal doxorubicin; Paclitaxel; Cyclophosphamide; Bevacizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

pilot study

Results Point of Contact

• Title: John Carpenter, M.D.
• Organization: UAB

jtc4321@bellsouth.net

205-910-8886 or 205-934-2084

Study Officials

• John Carpenter, M.D.

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Medicine

Study Record Dates

• First Submitted: March 6, 2008
• First Posted: March 13, 2008
• Study Start: March 1, 2008
• Primary Completion: December 1, 2014
• Study Completion: June 1, 2015
• Last Updated: July 14, 2016
• Results First Posted: June 15, 2016

Record last verified: 2016-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)