A Study of Biweekly Gemcitabine, Paclitaxel, and Avastin in Patients With Metastatic Breast Cancer

Condition(s) targeted: Metastatic Breast Cancer

Intervention: Paclitaxel (Drug); Gemcitabine (Drug); Avastin (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: University of Cincinnati

Official(s) and/or principal investigator(s):
Kathleen Havlin, MD, Principal Investigator, Affiliation: University of Cincinnati

Overall contact:
Tammy S Roads, Phone: 513-558-2192, Email: roadst@ucmail.uc.edu

The purpose of this study is to look at a new chemotherapy schedule in metastatic breast cancer.

Official title: A Phase II Trial of Biweekly Gemcitabine, Paclitaxel, and Avastin as Frontline Therapy for Metastatic Breast Cancer

Study design: Treatment, Non-Randomized, Open Label, Active Control, Single Group Assignment, Safety/Efficacy Study

Primary outcome: To assess the progression-free survival in patients receiving biweekly Paclitaxel + Gemcitabine + Avastin as first-line therapy for metastatic breast cancer.

Secondary outcome: To estimate the overall response rate (OPR-complete and partial) in the subset of patients with measurable disease, overall survival (OS) at 3 years and to assess the toxicity of the combination therapy.

Detailed description: The purpose of this study is to determine whether a new chemotherapy schedule using biweekly combination of paclitaxel (Taxol®), gemcitabine (Gemzar®) and Avastin would help to lessen in-between-cycle growth of resistant cells and to evaluate the toxicity of this therapy.

Taxol is approved by the Food and Drug Administration (FDA) for use in metastatic breast and metastatic ovarian cancer but its use in this study is investigational. Gemzar is FDA approved for the use in breast, lung and pancreatic cancer but its use in this study is investigational.

The Avastin being given in this study is commercially available, however, it has not been approved by FDA for use in metastatic breast cancer.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Patient must be 18 years of age or older with histologically confirmed breast

cancer and clinical evidence of metastatic disease.

- Patients must have measurable or non-measurable disease. X-rays, scans or physical

examinations used to assess measurable disease must be performed within 28 days prior to registration. X-rays, scans or physical examinations to assess non-measurable disease must be completed within 42 days prior to registration. Patients with effusions or ascites as the only sites of disease are ineligible.

- Patients must meet the following requirements regarding prior and concurrent

chemotherapy: Patients must not have received prior chemotherapy regimens for metastatic breast cancer. Patients may have received adjuvant/neoadjuvant chemotherapy, for a total of 3 prior regimens.

- Prior therapy with paclitaxel or docetaxel is allowed in the adjuvant or neoadjuvant

setting, if given > 6 months prior to registration.

- Patients must have >14 days delay between the conclusion of any radiation and the

start of gemcitabine, provided the acute effects of radiation treatment have resolved.

- Patients may have received any number of exogenous hormonal therapies and/or

trastuzumab in the adjuvant, neoadjuvant or metastatic setting. Last dose of prior hormonal therapy at least 14 days prior to registration.

- Patients may receive concomitant bisphosphonate therapy for bone metastasis.

- Patients must have recovered from any prior surgery. Two weeks must have elapsed from

the time of any minor surgery and 4 weeks of any major surgery.

- Patients must have adequate bone marrow reserve as evidenced by the following: ANC >

1500/mcL, platelets > 100, 000/mcL, and hemoglobin > 9. 0 gm/dL. These results must be obtained within 28 days prior to registration.

- Patients must have serum creatinine < 1. 5 mg/dL, obtained within 28 days prior to

registration.

- Urine Protein: creatinine ratio ≥ 1. 0 at screening.

- Patients must have adequate liver function.

- Patients must have a Zubrod performance status of 0-1.

Exclusion Criteria:

- Patients must not have tumors that carry HER-2 gene amplifications as determined by

(i) fluorescence in situ hybridization (FISH) or (ii) overexpression of HER-2 protein 3+ level assessed by immunohistochemistry; or may have tumors that carry HER=2 gene amplification and have had disease progression while on trastuzumab. Patients who have previously been treated with trastuzumab must be off treatment at least 28 days prior to registration.

- Patients must not have CNS metastasis, leptomeningeal disease or lymphatic pulmonary

metastases.

- Patients must not have had prior therapy with gemcitabine or bevacizumab.

- Patient must not have major surgical procedure, open biopsy, or significant traumatic

injury within 28 days prior to start of treatment, anticipation of need for major surgical procedure during the course of the study.

- Patients must not have received radiation to > 50% of the marrow-bearing bone.

- Patients must not have a history of significant symptomatic cardiac disease or left

ventricular ejection fraction (LVEF) < 50% of the institutional lower limit of normal (ILLN). An isotope cardiac scan (MUGA) and ECG must be obtained within 28 days.

- Patients with uncontrolled hypertension are NOT eligible (BP>150/100).

- Patients must not have pr-existing clinically significant (Grade 2 or greater per

CTCAE Version 3. 0 motor or sensory neuropathy except for abnormalities due to cancer.

- Patients known to be HIV positive.

- Patients must not be nursing or pregnant. Men and women of reproductive potential must

agree to use an effective contraceptive method.

- No other prior malignancy is allowed except for the following: adequately treated

basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or Stage II cancer from which the patient has been disease free for 5 years.

- Patients must not have had a Stroke or Myocardial Infarction in the past 6 months.

Patients with unstable agina, significant peripheral vascular disease, history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within the last 6 months should be excluded.

Tammy S Roads, Phone: 513-558-2192, Email: roadst@ucmail.uc.edu

University of Cincinnati Dept. of Medicine, Div. Hem/Onc, Cincinnati, Ohio 45267, United States; Recruiting
Ruth Steele, BS, EMT-P, Phone: 513-584-2951, Email: ruth.steele@uc.edu
Tammy Roads, Phone: 513-558-2192, Email: roadst@ucmail.uc.edu
Kathleen Havlin, MD, Principal Investigator

Starting date: November 2006
Ending date: November 2011
Last updated: August 13, 2008