This phase II trial studies capecitabine and lapatinib ditosylate to see how well they work compared with capecitabine, lapatinib ditosylate, and cixutumumab in treating patients with previously treated HER2-positive stage IIIB-IV breast cancer. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with cixutumumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether capecitabine and lapatinib ditosylate are more effective when given with or without cixutumumab in treating breast cancer that has spread nearby or to other areas of the body.
PRIMARY OBJECTIVE: I. To compare progression-free survival of HER2+ breast cancer patients randomized to receive lapatinib ditosylate (lapatinib) and capecitabine +/- cixutumumab (IMC-A12). SECONDARY OBJECTIVES: I. To assess the safety and tolerability of lapatinib and capecitabine +/- IMC-A12 in HER2+ breast cancer patients. II. To compare the overall survival time, time to treatment failure, confirmed tumor response rate, and duration of response of lapatinib and capecitabine +/- IMC-A12 in HER2+ breast cancer patients. III. To assess patient compliance per treatment arm and to compare overall quality of life and treatment side effects via patient-reported outcomes between treatment arms. TRANSLATIONAL RESEARCH OBJECTIVES: I. To determine the role of the following in predicting response to lapatinib and capecitabine +/- IMC-A12: Ia. Expression patterns and/or activation IGF- and ErbB family of receptors and signaling molecules in formalin-fixed, paraffin-embedded breast tumor tissue. Ib. Expression patterns and/or activation IGF- and ErbB receptors and signaling molecules in circulating tumor cells from breast cancer patients. Ic. Changes in expression patterns and/or activation IGF- and ErbB receptors and signaling molecules following treatment with lapatinib and capecitabine +/- IMC-A12 in circulating tumor cells from breast cancer patients. Id. Expression patterns of IGF-1, IGF-II, insulin, growth hormone, and the IGF binding proteins in the serum of breast cancer patients. Ie. Changes in expression patterns of IGF-1, IGF-II, insulin, growth hormone, and the IGF binding proteins in the serum of breast cancer patients. II. Banking of paraffin-embedded tissue blocks/slides and blood products (i.e., serum, plasma, and buffy coat) for future studies. III. To assess the proportion of patients whose pathologic specimens were correctly diagnosed as HER2 positive (according to 2007 American Society of Clinical Oncology \[ASCO\] College of American Pathologist \[CAP\] guidelines) metastatic breast cancer. OUTLINE: The first 10 patients enrolled on this study are assigned to cohort I (safety analysis). All other patients are assigned to cohort II (randomized treatment). COHORT I (SAFETY ANALYSIS, closed to accrual): Patients receive cixutumumab intravenously (IV) over 1 hour on days 1, 8, and 15. Patients also receive capecitabine orally (PO) twice daily (BID) on days 1-14 and lapatinib ditosylate PO once daily (QD) on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. COHORT II (RANDOMIZED TREATMENT): Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive capecitabine PO BID on days 1-14 and lapatinib ditosylate PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive capecitabine and lapatinib ditosylate as in Arm A. Patients also receive cixutumumab IV over 1 hour on days 1, 8, and 15. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months until disease progression and then every 6 months for up to 5 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
64
Providence Hospital
Mobile, Alabama, United States
Mayo Clinic in Arizona
Scottsdale, Arizona, United States
Alta Bates Summit Medical Center-Herrick Campus
Berkeley, California, United States
Mills-Peninsula Medical Center
Burlingame, California, United States
East Bay Radiation Oncology Center
Castro Valley, California, United States
Progression-free Survival (PFS)
Analysis of the primary endpoint, PFS, will be performed using Cox regression with treatment group as a single covariate.
Time frame: From randomization to the earliest date of documentation of disease progression, up to 5 years
Overall Survival
Median Survival time (months)
Time frame: From randomization to death due to any cause, up to 5 years
Time to Treatment Failure
Distribution estimated by the Kaplan-Meier (1958) method for each treatment arm.
Time frame: From the date of randomization to the date at which the patient is removed from treatment due to progression, adverse events, or refusal, up to 5 years
Confirmed Tumor Response, Defined as Either a Complete Response (CR) or Partial Response (PR) Noted as the Objective Status on 2 Consecutive Evaluations at Least 6 Weeks Apart, Assessed by Response Evaluation Criteria for Solid Tumors (RECIST)
Time frame: Up to 5 years
Duration of Response
Distribution estimated by the Kaplan-Meier (1958) method for each treatment arm.
Time frame: Up to 5 years
Adverse Event Profile of Capecitabine and Lapatinib With and Without IMC-A12 (Using NCI CTCAE v3.0)
All eligible patients that have initiated treatment will be considered evaluable for assessing adverse event rate(s) according to CTCAE v3.0 within each treatment arm. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. 4/19 (21.05%) 14/45 (31.11%)
Time frame: Baseline to 30 days past end of treatment
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Eden Hospital Medical Center
Castro Valley, California, United States
Valley Medical Oncology Consultants-Castro Valley
Castro Valley, California, United States
Bay Area Breast Surgeons Inc
Emeryville, California, United States
Valley Medical Oncology Consultants-Fremont
Fremont, California, United States
Glendale Memorial Hospital and Health Center
Glendale, California, United States
...and 380 more locations