Capecitabine and Lapatinib With or Without Cixutumumab in Treating Patients With Previously Treated HER2-Positive Stage IIIB, Stage IIIC, or Stage IV Breast Cancer

This study is ongoing, but not recruiting participants.
Southwest Oncology Group
Information provided by (Responsible Party):
National Cancer Institute (NCI) Identifier:
First received: May 22, 2008
Last updated: October 1, 2014
Last verified: December 2013

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.

Condition Intervention Phase
HER2-positive Breast Cancer
Male Breast Cancer
Recurrent Breast Cancer
Stage IIIB Breast Cancer
Stage IIIC Breast Cancer
Stage IV Breast Cancer
Biological: cixutumumab
Drug: lapatinib ditosylate
Drug: capecitabine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Progression-free Survival (PFS) [ Time Frame: From randomization to the earliest date of documentation of disease progression, up to 5 years ] [ Designated as safety issue: No ]
    Analysis of the primary endpoint, PFS, will be performed using Cox regression with treatment group as a single covariate.

Secondary Outcome Measures:
  • Overall Survival [ Time Frame: From randomization to death due to any cause, up to 5 years ] [ Designated as safety issue: No ]
    Median Survival time (months)

  • 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 ] [ Designated as safety issue: No ]
    Distribution estimated by the Kaplan-Meier (1958) method for each treatment arm.

  • 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 ] [ Designated as safety issue: No ]
  • Duration of Response [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Distribution estimated by the Kaplan-Meier (1958) method for each treatment arm.

  • Adverse Event Profile as Assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]

Enrollment: 64
Study Start Date: July 2008
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I (lapatinib ditosylate, capecitabine)
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.
Drug: lapatinib ditosylate
Given PO
Other Names:
  • GSK572016
  • GW-572016
  • GW2016
  • Lapatinib
  • Tykerb
Drug: capecitabine
Given PO
Other Names:
  • CAPE
  • Ro 09-1978/000
  • Xeloda
Active Comparator: Arm II (cixutumumab, lapatinib ditosylate, capecitabine)
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.
Biological: cixutumumab
Given IV
Other Names:
  • anti-IGF-1R recombinant monoclonal antibody IMC-A12
  • IMC-A12
Drug: lapatinib ditosylate
Given PO
Other Names:
  • GSK572016
  • GW-572016
  • GW2016
  • Lapatinib
  • Tykerb
Drug: capecitabine
Given PO
Other Names:
  • CAPE
  • Ro 09-1978/000
  • Xeloda

  Show Detailed Description


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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 anthracycline and/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, intense staining of > 30% of invasive tumor cells)
    • Average HER2 gene copy number > 6
    • Gene amplified (HER2:D17Z1 ratio > 2.20)
  • Measurable disease according to Response Evaluation Criteria in Solid Tumors (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
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Life expectancy > 3 months
  • white blood cell count (WBC) ≥ 3,000/mm³
  • absolute neutrophil count (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 cancer or carcinoma in situ of the cervix

    • History of prior malignancy allowed provided patient is not receiving other specific treatment for their malignancy
  • No current, active hepatic or biliary disease, except Gilbert syndrome's or asymptomatic 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 study requirements
  • 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 (either monoclonal antibody or tyrosine kinase inhibitor) including, but not limited to, any of 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00684983

  Show 366 Study Locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Southwest Oncology Group
Principal Investigator: Paul Haluska North Central Cancer Treatment Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI) Identifier: NCT00684983     History of Changes
Other Study ID Numbers: NCI-2009-00665, NCI-2009-00665, CDR0000596070, NCCTG-N0733, N0733, N0733, U10CA025224
Study First Received: May 22, 2008
Results First Received: October 1, 2014
Last Updated: October 1, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

Additional relevant MeSH terms:
Breast Neoplasms
Breast Neoplasms, Male
Breast Diseases
Neoplasms by Site
Skin Diseases
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protein Kinase Inhibitors
Therapeutic Uses processed this record on October 08, 2015