Metastatic Breast Cancer
Conditions
Keywords
Breast cancer
Brief summary
The purpose of this study is to look at a new chemotherapy schedule in metastatic breast cancer.
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.
Interventions
DRUGPaclitaxel
Patients will be premedicated with dexamethasone and diphenhydramine hydrochloride. Patients will received 150mg of paclitaxel via IV over 120 mins.
DRUGGemcitabine
Patients will receive 1500mg of Gemcitabine via IV over 30-60 minutes. Gemcitabine will be given after Paclitaxel.
DRUGAvastin
10mg/kg will be given via IV over 90 mins (1st dose). Patients must remain under supervision for 1 hr after completion of the initial dose of Avastin. If no side effects occur, shortened, 60-min 2nd infusion, the post-infusion observation period for the subsequent infusions may be shortened to 20 minutes, and eliminated entirely with the fourth and subsequent infusions.
Sponsors
Eli Lilly and Company
Genentech, Inc.
Barbara Ann Karmanos Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | maximum 50 months | Time from study entry to disease progression or death |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | maximum 50 months | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) at 3 Years | 3 years | proportion of participants surviving 3 years |
| Toxicity | Duration of study | toxicities recorded using CTCAE definitions |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Period Treatment will be administered once every 2 weeks. One cycle of therapy will consist of 14 days. Paclitaxel is administered first after appropriate premedications. Gemcitabine is administered second and Avastin is administered after chemotherapy, all given on day 1 of each cycle.
Paclitaxel: Patients will be premedicated with dexamethasone and diphenhydramine hydrochloride. Patients will received 150mg of paclitaxel via IV over 120 mins.
Gemcitabine: Patients will receive 1500mg of Gemcitabine via IV over 30-60 minutes. Gemcitabine will be given after Paclitaxel.
Avastin: 10mg/kg will be given via IV over 90 mins (1st dose). Patients must remain under supervision for 1 hr after completion of the initial dose of Avastin. If no side effects occur, shortened, 60-min 2nd infusion, the post-infusion observation period for the subsequent infusions may be shortened to 20 minutes, and eliminated entirely with the fourth and subsequent infusions. | 14 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Treatment Period |
|---|---|
| Age, Continuous | 53.5 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Region of Enrollment United States | 14 participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 14 / 14 |
| serious Total, serious adverse events | 10 / 14 |
Outcome results
Primary
Progression-free Survival
Time from study entry to disease progression or death
Time frame: maximum 50 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment | Progression-free Survival | 43 months |
Secondary
Overall Response Rate
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: maximum 50 months
Population: patients with measurable disease
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Overall Response Rate | 0.46 proportion of participants |
Other Pre-specified
Overall Survival (OS) at 3 Years
proportion of participants surviving 3 years
Time frame: 3 years
Other Pre-specified
Toxicity
toxicities recorded using CTCAE definitions
Time frame: Duration of study