Predicting Response and Toxicity in Patients Receiving Paclitaxel and Avastin for Breast Cancer

This study has been terminated.
(Lack of Accrual)
Sponsor:
Collaborators:
Indiana University School of Medicine
University of Colorado, Denver
Baylor University
McGill University
Information provided by:
Hoosier Oncology Group
ClinicalTrials.gov Identifier:
NCT00537173
First received: September 26, 2007
Last updated: April 27, 2011
Last verified: April 2011
  Purpose

This trial provides a unique opportunity in that it combines genomic, proteomic and pharmacogenomic assessments in patients receiving chemotherapy for advanced breast cancer. To date no other trials have analyzed gene and protein expression at the same time points in the same patient, combined with clinical outcome. Similar to previous attempts to predict response based on expression of a single gene or protein, we expect that neither genomic or proteomic profiling alone will be sufficient to optimize therapy. Rather, we expect an iterative process that combines information gleaned from both platforms, modified to avoid toxicity based on pharmacogenomics.


Condition Intervention
Breast Cancer
Procedure: Core Biopsy
Procedure: Blood Collection
Drug: Paclitaxel
Drug: Avastin

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Predicting Response and Toxicity in Patients Receiving Paclitaxel and Avastin for Breast Cancer: A Multicenter Genomic, Proteomic and Pharmacogenomic Correlative Study

Resource links provided by NLM:


Further study details as provided by Hoosier Oncology Group:

Primary Outcome Measures:
  • To correlate tumor gene expression (genomic profile) with response to paclitaxel + Avastin in patients with advanced breast cancer [ Time Frame: 36 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To correlate serum and tumor proteomic profiles with response; To compare serum and tissue proteomic analyses; To compare genomic and proteomic profiles; To correlate toxicity and/or response with drug-specific pharmacogenomic parameters. [ Time Frame: 36 months ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Blood and tumor samples


Enrollment: 11
Study Start Date: September 2007
Study Completion Date: August 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Arm 1
Paclitaxel 90 mg/m2 IV D1, 8, and 15 + Avastin 10 mg/kg IV, day 1 and 15
Procedure: Core Biopsy
biopsy
Procedure: Blood Collection
Blood/serum sample
Drug: Paclitaxel
Paclitaxel 90 mg/m2 IV, day 1, 8 and 15
Drug: Avastin
Avastin 10 mg/kg IV, day 1 and 15

Detailed Description:

OUTLINE: This is a multi-center study.

Sample Collection:

  • Core biopsy
  • Blood sample

    28-day Cycle Treatment Regimen:

  • Paclitaxel 90 mg/m2 IV D1, 8, and 15
  • Avastin 10 mg/kg IV D1 and 15

ECOG Performance Status of 0 or 1

Life Expectancy: Not specified

Hematopoietic:

  • Platelet count > 100,000/mm³
  • Absolute neutrophil count > 1200/mm³
  • PTT < 1.5 x upper limit of normal
  • INR < 1.5 x upper limit of normal

Hepatic:

  • Total bilirubin < 1.5 mg/dL
  • SGOT (AST) < 2 x upper limit of normal

Renal: Not specified

Cardiovascular:

  • Clinically significant cardiovascular or cerebrovascular disease including prior myocardial infarction (within 6 months prior to study entry), unstable angina, Grade II or greater peripheral vascular disease, New York Heart Association (NYHA) Grade II or greater congestive heart failure, hypertensive crises, hypertensive encephalopathy or uncontrolled hypertension (SBP>150, DBP>100).
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Study population is limited to patients with advanced breast cancer who are receiving paclitaxel + Avastin

Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed adenocarcinoma of the breast with measurable locally recurrent, locally advanced (that is not amenable to resection with curative intent), or metastatic disease.
  • Patients must consent to have a biopsy performed to obtain fresh tissue or be able to identify a FFPE tissue block in which tissue samples can be obtained to complete the testing for this study.
  • Planned chemotherapy regimen of paclitaxel and Avastin for the treatment of metastatic breast cancer.
  • Females age > 18 years
  • Written informed consent and HIPAA authorization for release of personal health information.

Exclusion Criteria:

  • Patients must not have had chemotherapy for locally recurrent or metastatic breast cancer.
  • Hormonal therapy for locally recurrent or metastatic disease must have been discontinued at least 2 weeks prior to study entry.
  • Patients must not have had adjuvant or neoadjuvant taxane therapy within 12 months prior to study entry.
  • Breast cancer overexpressing HER-2 (gene amplification by FISH or 3+ overexpression by immunohistochemistry) are not eligible unless they have received prior therapy with Herceptin.
  • Patients must not have had a major surgical procedure within 4 weeks prior to study entry. (Placement of vascular access device, and breast biopsy, will not be considered major surgery.)
  • Patients must not have had a minor surgical procedure, placement of an access device, or fine needle aspiration within 7 days of starting protocol therapy.
  • Patients must not have had radiation within 2 weeks prior to study entry.
  • Previously radiated area(s) must not be the only site of disease for study entry.
  • Patients must not have a history of bleeding diathesis or have used anticoagulant therapy within 10 days of study entry. (Low dose anticoagulant therapy to maintain patency of a vascular access device is allowed.)
  • Patients with a history of deep vein thrombosis or pulmonary embolism are not eligible.
  • Aspirin usage (> 325 mg/day) or other nonsteroidal anti-inflammatory medications known to inhibit platelet function daily are not allowed within 10 days prior to study entry.
  • Patients currently using any of the following drugs known to inhibit platelet function are not eligible: dipyridamole (Persantine), ticlopidine (Ticlid), clopidogrel (Plavix) and cilostazol (Pletal).
  • Patients must not have a history of TIA or CVA within 6 months prior to study entry.
  • Patients must not have a history or radiologic evidence of CNS metastases including previously treated, resected or asymptomatic brain lesions or leptomeningeal involvement (head CT or MRI must be obtained within 6 weeks prior to study entry).
  • Patients must not have a non-healing wound or fracture.
  • Patients must not have a hypersensitivity to paclitaxel or drugs using the vehicle Cremophor, Chinese hamster ovary cell products or other recombinant human antibodies.
  • Females must not be pregnant or breastfeeding. Females of childbearing potential must use an accepted and effective method of contraception (hormonal or barrier method of birth control; abstinence) while on treatment and for a 3 month period thereafter.
  • Females of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for protocol therapy. Subjects are considered not of child bearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal.
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study entry
  • Urine protein: creatinine (UPC) ratio > 1.0 at baseline or urine protein dipstick > 2+.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00537173

Locations
United States, Indiana
Cancer Care Center of Southern Indiana
Bloomington, Indiana, United States, 47403
Indiana University Simon Cancer Center
Indianapolis, Indiana, United States, 46202
Horizon Oncology Center
Lafayette, Indiana, United States, 47905
United States, Texas
Baylor College of Medicine - Methodist Breast Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Hoosier Oncology Group
Indiana University School of Medicine
University of Colorado, Denver
Baylor University
McGill University
Investigators
Principal Investigator: George Sledge, M.D. Hoosier Oncology Group, Inc.
  More Information

Additional Information:
No publications provided

Responsible Party: Kathy Miller, M.D., Hoosier Oncology Group
ClinicalTrials.gov Identifier: NCT00537173     History of Changes
Other Study ID Numbers: HOG COE-02, DoD Grant BC030400
Study First Received: September 26, 2007
Last Updated: April 27, 2011
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Bevacizumab
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on April 17, 2014