Breast Cancer
Conditions
Keywords
recurrent breast cancer, stage IV breast cancer, male breast cancer
Brief summary
RATIONALE: Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining erlotinib with docetaxel may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining erlotinib with docetaxel in treating patients who have stage IV or recurrent breast cancer.
Detailed description
OBJECTIVES: * Determine the antitumor effects of erlotinib and docetaxel, in terms of objective response, stabilization of disease, and progression-free survival, in patients with stage IV or recurrent breast cancer. * Determine time to tumor progression in patients treated with this regimen. * Compare time to tumor progression in patients who achieve disease stabilization or response after treatment with this regimen and continue to receive erlotinib versus patients who do not receive additional erlotinib. OUTLINE: Patients receive docetaxel IV over 1 hour once weekly for 3 weeks and oral erlotinib once daily beginning on day 1. Treatment repeats every 4 weeks for a minimum of 6 courses in the absence of unacceptable toxicity or disease progression. Patients achieving maximal tumor response or stabilization of disease after 6 courses may continue to receive erlotinib alone until disease progression. Patients are followed for survival. PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study within 12-14 months.
Interventions
DRUGdocetaxel
Docetaxel IV infusion weekly for 3 weeks with a one-week break. One cycle is 4 weeks (28 days). Patients' actual weight will be used to calculate dose.
DRUGerlotinib hydrochloride
OSI-774 will be taken 1 hour before or 2 hours after meals. Cycle 1 will be administered at dose level -1.If no grade 3 or 4 toxicity occurs during cycle 1, then the patient may proceed to be treated at dose level 0 for the remaining chemotherapy cycles.
Sponsors
National Cancer Institute (NCI)
Paula Silverman, MD
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
DISEASE CHARACTERISTICS: * Histologically confirmed stage IV or recurrent adenocarcinoma of the breast * Measurable disease * Disease recurrence must not be within 1 year of receiving prior adjuvant docetaxel * Stable brain metastases allowed * Hormone receptor status: * Not specified PATIENT CHARACTERISTICS: Age * 18 and over Sex * Male or female Menopausal status * Not specified Performance status * ECOG (Eastern Cooperative Oncology Group) 0-2 OR * Karnofsky 60-100% Life expectancy * More than 6 months Hematopoietic * WBC(White Blood Count) at least 3,000/mm\^3 * Platelet count at least 100,000/mm\^3 * Absolute neutrophil count at least 1,500/mm\^3 * Hemoglobin at least 8 g/dL Hepatic * Bilirubin normal * AST(aspartate aminotransferase)/ALT(alanine aminotransferase) no greater than 2.5 times upper limit of normal Renal * Creatinine normal OR * Creatinine clearance at least 60 mL/min * No clinically significant proteinuria * No significant impairment of renal function Cardiovascular * No New York Heart Association class III or IV heart disease * No symptomatic congestive heart failure * No unstable angina pectoris * No cardiac arrhythmia * No inadequately controlled hypertension Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective barrier contraception * No prior severe hypersensitivity reaction to docetaxel or drugs formulated with polysorbate 80 * No other malignancy within the past 10 years except inactive nonmelanoma skin cancer, carcinoma in situ of the cervix, carcinoma in situ of the breast, or bilateral breast cancer * No ongoing or active infection * No peripheral neuropathy greater than grade 1 * No other concurrent uncontrolled medical condition that would preclude study participation * No psychiatric illness or social situation that would preclude study compliance PRIOR CONCURRENT THERAPY: Biologic therapy * Prior trastuzumab (Herceptin) allowed Chemotherapy * See Disease Characteristics * No prior chemotherapy for recurrent or metastatic disease * Prior adjuvant chemotherapy allowed Endocrine therapy * Prior hormonal therapy allowed Radiotherapy * Not specified Surgery * Not specified Other * No other concurrent investigational agents
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease Response (Tumor Measurements)Per RECIST Criteria v. 2000 | after 6 course (6 months) of combination therapy | Response and progression will be evaluated in this study using the criteria by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in the RECIST criteria. Partial Response: At least a 30% decrease in the sum of the longest diameter (LD) of target lesions. Progressive Disease: At least a 20% increase in the sum of the LD of target lesions. Stable Disease: Neither sufficient shrinkage nor sufficient increase. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival(PFS) | 3 years | Progression free survival was defined as time from the start of treatment to the date of cancer progression, or death, and censored at the date of last follow-up for those without disease progression and still alive. Stable disease is measured from the start of the treatment until progression, taking as reference the smallest measurements recorded since the treatment started. Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. |
| Overall Survival as of 2008 | 5 yrs | Overall survival (OS) was defined as time from the start of treatment to death, and censored at the time of last assessment for survivors. |
Countries
United States
Participant flow
Recruitment details
Patients recruited from University Hospitals and its satellite hospitals from 12/4/2002 through 9/22/2006.
Participants by arm
| Arm | Count |
|---|---|
| Docetaxel and OSI-774 docetaxel IV over 1 hour once weekly for 3 weeks and oral erlotinib once daily | 39 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 5 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Progressive disease in cycle 1 | 1 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Docetaxel and OSI-774 |
|---|---|
| Age, Continuous | 51 years |
| Region of Enrollment United States | 39 participants |
| Sex: Female, Male Female | 39 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 | 39 / 39 |
| serious Total, serious adverse events | 28 / 39 |
Outcome results
Primary
Disease Response (Tumor Measurements)Per RECIST Criteria v. 2000
Response and progression will be evaluated in this study using the criteria by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in the RECIST criteria. Partial Response: At least a 30% decrease in the sum of the longest diameter (LD) of target lesions. Progressive Disease: At least a 20% increase in the sum of the LD of target lesions. Stable Disease: Neither sufficient shrinkage nor sufficient increase.
Time frame: after 6 course (6 months) of combination therapy
Population: Excluding 11 not evaluable cases
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Docetaxel and OSI-774 | Disease Response (Tumor Measurements)Per RECIST Criteria v. 2000 | Partial response | 11 participants |
| Docetaxel and OSI-774 | Disease Response (Tumor Measurements)Per RECIST Criteria v. 2000 | Disease progression | 14 participants |
| Docetaxel and OSI-774 | Disease Response (Tumor Measurements)Per RECIST Criteria v. 2000 | Stable disease | 3 participants |
p-value: 0.9595% CI: [0.23, 0.58]confidence interval for partial response
Secondary
Overall Survival as of 2008
Overall survival (OS) was defined as time from the start of treatment to death, and censored at the time of last assessment for survivors.
Time frame: 5 yrs
Population: Including 10 patients with only 1 cycle of treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Docetaxel and OSI-774 | Overall Survival as of 2008 | 22.3 months |
Secondary
Progression Free Survival(PFS)
Progression free survival was defined as time from the start of treatment to the date of cancer progression, or death, and censored at the date of last follow-up for those without disease progression and still alive. Stable disease is measured from the start of the treatment until progression, taking as reference the smallest measurements recorded since the treatment started. Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Time frame: 3 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Docetaxel and OSI-774 | Progression Free Survival(PFS) | 8.4 months |