Overview

This trial is active, not recruiting.

Conditions her2-positive breast cancer, male breast cancer, recurrent breast cancer, stage iiib breast cancer, stage iiic breast cancer, stage iv breast cancer
Treatments cixutumumab, lapatinib ditosylate, capecitabine
Phase phase 2
Sponsor National Cancer Institute (NCI)
Collaborator Southwest Oncology Group
Start date July 2008
End date December 2012
Trial size 154 participants
Trial identifier NCT00684983, CDR0000596070, N0733, NCCTG-N0733, NCI-2009-00665, U10CA025224

Summary

This randomized phase II trial is studying capecitabine and lapatinib to see how well they work compared with capecitabine, lapatinib, and cixutumumab in treating patients with previously treated HER2-positive stage IIIB, stage IIIC, or stage 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 or by stopping them from dividing. Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as cixutumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether capecitabine and lapatinib are more effective with or without monoclonal antibody therapy in treating locally advanced or metastatic breast cancer.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Active Comparator)
Patients receive oral capecitabine twice daily on days 1-14 and oral lapatinib ditosylate once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
lapatinib ditosylate GSK572016
Given PO
capecitabine CAPE
Given PO
(Active Comparator)
Patients receive capecitabine and lapatinib ditosylate as in arm I. Patients also receive cixutumumab IV over 1-1½ hours on days 1, 8, and 15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
cixutumumab anti-IGF-1R recombinant monoclonal antibody IMC-A12
Given IV
lapatinib ditosylate GSK572016
Given PO
capecitabine CAPE
Given PO

Primary Outcomes

Measure
Progression-free survival (PFS)
time frame: From randomization to the earliest date of documentation of disease progression, up to 5 years

Secondary Outcomes

Measure
Overall survival
time frame: From randomization to death due to any cause, up to 5 years
Time to treatment failure
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 CR or 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
time frame: Up to 5 years
Adverse event profile as assessed by NCI CTCAE v4.0
time frame: Up to 5 years

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Histologically confirmed breast cancer, meeting one of the following criteria: - Locally advanced disease (i.e., stage IIIB or IIIC [T4 primary tumor] disease) - Metastatic disease - Disease progressed after treatment with regimens that included trastuzumab (Herceptin®) in combination with an anthracycline and/or a taxane - Must have received 1-2 prior chemotherapy regimens in the neoadjuvant, adjuvant, or metastatic setting - One regimen must have included treatment with an anthracyclineand/or a taxane - Prior treatment with trastuzumab required unless there is a contraindication for trastuzumab treatment - HER2-positive disease, defined by any of the following: - Validated IHC assay score of 3+ (defined as uniform, intensestaining of > 30% of invasive tumor cells) - Average HER2 gene copy number > 6 - Gene amplified (HER2:D17Z1 ratio > 2.20) - Measurable disease according to RECIST criteria - No evidence of active brain metastases, including leptomeningeal involvement - CNSmetastasis controlled* by prior surgery and/or radiotherapy is allowed - Hormone receptor status not specified - Menopausal status not specified - ECOG performance status 0-2 - Life expectancy > 3 months - WBC ≥ 3,000/mm³ - ANC ≥ 1,500/mm³ - Platelet count ≥ 75,000/mm³ - Hemoglobin > 9.0 g/dL - Total bilirubin ≤ 1.5 times upper limit of normal (ULN) - AST and ALT ≤ 2.5 times ULN (5 times ULN if elevations are due to liver metastases) - Serum creatinine ≤ 1.5 times ULN - Creatinine clearance ≥ 30 mL/min - Fasting glucose < 120 mg/dL - Diabetes allowed provided blood glucose level meets the above criterion - INR ≤ 1.5 times ULN - LVEF ≥ 50% by MUGA or ECHO - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception - Willing to provide tissue and blood samples for research purposes - Able to complete questionnaires by self or with assistance - No other stage III or IV invasive cancer within the past 5 years - No other malignancy requiring active treatment, except nonmelanoma skin canceror carcinoma in situ of the cervix - History of prior malignancy allowed providedpatient is not receiving other specific treatment for their malignancy - No current, active hepatic or biliary disease, except Gilbert syndrome's orasymptomatic gallstones - No New York Heart Association class III or IV cardiovascular disease - No concurrent uncontrolled illness including, but not limited to, any of the following: - Poorly controlled diabetes - Ongoing or active infection - Symptomatic congestive heart failure - Unstable angina pectoris - Cardiac arrhythmia - Psychiatric illness/social situation that would preclude compliance with studyrequirements - No co-morbid systemic illness or other severe concurrent disease that, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of the safety of the prescribed study regimens - Not immunocompromised (other than that related to the use of corticosteroids), including known HIV-positivity with an AIDS-defining illness - HIV-positive patients with a CD4 count within normal range and who have no history of an AIDS-defining illness are eligible - No other concurrent chemotherapeutic agents, biologic agents, or radiotherapy - Prior hormonal therapy in the neoadjuvant, adjuvant, or metastatic setting allowed - More than 6 weeks since prior major surgery, chemotherapy, or immunologic therapy - More than 4 weeks since prior radiotherapy, except a single dose of palliative radiotherapy or radiotherapy to a non-target lesion - Prior radiotherapy to a target lesion is allowed only if there has been clear progression of the lesion since completion of radiotherapy - Recovered from prior radiotherapy - No more than 2 prior chemotherapy regimens for metastatic disease - No prior treatment with any therapy targeting IGF-I, IGF-II, or its receptors (eithermonoclonal antibody or tyrosine kinase inhibitor) including, but not limited to, anyof the following: - Cixutumumab - CP-751871 - AMG-479 - INSM-18 - MK-0646 (h7C10) - 19D12 - R1507 - OSI-906 - BMS-536924 - PPP - NVP-AEW541 - No other prior therapy targeting HER1 (EGFR) and/or HER2 (either monoclonal antibody or tyrosine kinase inhibitor) including, but not limited to, any of the following: - Lapatinib ditosylate - Gefitinib - Erlotinib hydrochloride - Cetuximab - Panitumumab - No concurrent agents that would contraindicate study treatment, including any of the following: - CYP3A4 inhibitors and inducers, including grapefruit and grapefruit juice - Warfarin, cimetidine,allopurinol, sorivudine or brivudine,ketoconazole, itraconazole, ritonavir,amprenavir, or indinavir - No concurrent treatment in another clinical study in which investigational procedures are performed or investigational therapies are administered

Additional Information

Official title Randomized Phase II Trial of Capecitabine and Lapatinib With or Without IMC-A12 in Patients With HER2 Positive Breast Cancer Previously Treated With Trastuzumab and an Anthracycline and/or a Taxane
Principal investigator Paul Haluska
Description PRIMARY OBJECTIVES: I. To compare progression-free survival of HER2+ breast cancer patients randomized to receive lapatinib and capecitabine +/- 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. TERTIARY OBJECTIVES: I. To determine the role of the following in predicting response to lapatinib and capecitabine +/- IMC-A12: II. Expression patterns and/or activation IGF- and ErbB family of receptors and signaling molecules in formalin-fixed, paraffin-embedded breast tumor tissue. III. Expression patterns and/or activation IGF- and ErbB receptors and signaling molecules in circulating tumor cells from breast cancer patients. IV. 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. V. Expression patterns of IGF-1, IGF-II, insulin, growth hormone, and the IGF binding proteins in the serum of breast cancer patients. VI. Changes in expression patterns of IGF-1, IGF-II, insulin, growth hormone, and the IGF binding proteins in the serum of breast cancer patients. VII. As part of ongoing research for NCCTG breast studies, we are banking paraffin-embedded tissue blocks/slides and blood products (i.e., serum, plasma, and buffy coat) for future studies. VIII. To assess the proportion of patients whose pathologic specimens were correctly diagnosed as HER2 positive (according to 2007 ASCO CAP guidelines) metastatic breast cancer. OUTLINE: This is a multicenter study. Patients are stratified according to hormone receptor status (estrogen receptor- or progesterone receptor-positive vs other) and number of prior chemotherapy regimens in the metastatic setting (2 vs 1 vs none). The first 10 patients enrolled on this study are assigned to cohort 1 (safety analysis). All other patients are assigned to cohort 2 (randomized treatment). COHORT 1 (SAFETY ANALYSIS): Patients receive cixutumumab IV over 1-1½ hours on days 1, 8, and 15. Patients also receive oral capecitabine twice daily on days 1-14 and oral lapatinib ditosylate once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. COHORT 2 (RANDOMIZED TREATMENT): Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive oral capecitabine twice daily on days 1-14 and oral lapatinib ditosylate once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive capecitabine and lapatinib ditosylate as in arm I. Patients also receive cixutumumab IV over 1-1½ hours on days 1, 8, and 15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Blood samples are collected at baseline and on day 8 of courses 1 and 2 for biomarker laboratory studies. Serum and circulating tumor cell biomarkers are analyzed by immunohistochemistry or immunofluorescence for changes in protein expression (total and phosphorylated). Tumor tissue samples obtained at the time of original diagnosis are analyzed by immunohistochemistry for protein biomarkers. Patients complete quality of life questionnaires periodically. After completion of study treatment, patients are followed every 3 months until disease progression and then every 6 months for up to 5 years.
Trial information was received from ClinicalTrials.gov and was last updated in December 2013.
Information provided to ClinicalTrials.gov by National Cancer Institute (NCI).