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Breast CancerPhase 3NCT00078572

Capecitabine (XELODA) With Or Without Lapatinib (GW572016) For Women With Refractory Advanced or Metastatic Breast Cancer

A Phase 3 study testing capecitabine and lapatinib (GW572016) in people with Breast Cancer, run by GlaxoSmithKline.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study was designed to compare the efficacy and safety of an oral dual tyrosine kinase inhibitor in combination with capecitabine versus capecitabine alone in women with locally advanced or metastatic breast cancer that has not responded to previous therapy. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer
What is being tested?
capecitabine and lapatinib (GW572016)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
408 participants
Where
No sites listed yet
Study dates
Mar 2004to Feb 2010
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed informed consent
  • Patients must have histologically confirmed invasive breast cancer with stage IIIb, stage IIIc with T4 lesion, or stage IV disease
  • Documentation of ErbB2 overexpression (immunohistochemistry (IHC) 3+ or IHC 2+ with fluorescence in situ hybridization (FISH) confirmation) is required based on local laboratory or initial diagnostic results. Where testing is not feasible, central laboratory testing will be utilized
  • Subjects must have documented progressive advanced or metastatic breast cancer. Progression for entry is defined as appearance of any new lesion not previously identified or increase of 25% or more in existent lesions and must be documented
  • Subjects must have refractory breast cancer defined as progression in the locally advanced or metastatic setting or relapse within 6 months of completing adjuvant therapy. Prior therapies must include, but are not limited to:
  • Taxane containing regimen for at least 4 cycles or 2 cycles provided disease progression occurred while on taxane
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  • Anthracycline containing regimen for at least 4 cycles or 2 cycles provided disease progression occurred while on anthracycline
  • Subjects who relapse > 6 months after completion of adjuvant anthracycline-containing chemotherapy, and for whom further anthracycline is not indicated, will be considered to have met the anthracycline prior exposure requirement
  • Taxanes and Anthracyclines may have been administered concurrently or separately
  • Prior treatment with capecitabine is not permitted
  • Prior treatment must have contained trastuzumab (Herceptin) alone or in combination with other chemotherapy for at least 6 weeks of standard doses in the locally advanced or metastatic setting. Trastuzumab administered in the adjuvant setting is not exclusionary, but for eligibility trastuzumab must also have been administered in the locally advanced or metastatic setting.
  • Subjects with hormone receptor positive tumors must have disease progression following hormonal therapy unless intolerant to hormonal therapy or hormonal therapy is not considered to be clinically appropriate
  • Subjects with stable central nervous system (CNS) metastases (asymptomatic and off systemic steroids and anticonvulsants for at least 3 months) are eligible
  • Female subjects must be≥18 years of age
  • Eastern Cooperative Oncology Group (ECOG Performance Status of 0 or 1
  • Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST)
  • Subjects must have archived tumor tissue available to re-evaluate intra-tumoral expression levels of ErbB1 and ErbB2 by IHC and FISH testing performed by the study central laboratory. Central laboratory results will not be used to determine subject eligibility for the study, unless testing is being used for required documentation of ErbB2 overexpression.
  • Life expectancy of ≥12 weeks
  • Subjects must have recovered from clinically significant side effects associated with prior radiotherapy and chemotherapy
  • Measurable lesions may be in the field of prior irradiation. However, there must be at least a 4-week period between the last radiation treatment and the baseline scan documenting disease status for the lesion to be measurable
  • Cardiac ejection fraction within the institutional range of normal as measured by echocardiogram (multigated acquisition (MUGA) scan may be performed if ECHO is not available)
  • Able to swallow and retain oral medication
  • Subjects must complete all screening assessments as outlined in the protocol
  • Adequate renal function defined as a Creatinine Clearance ≥50mL/min, determined by calculated creatinine clearance using Cockcroft and Gault Method and normalized to Body Surface Area (BSA)
  • Adequate hematologic and hepatic function as defined in Table 1:
  • Table 1 (Body System and Adequate Function Definitions) SYSTEM (LABORATORY VALUES)
  • Hematologic:
  • ANC (absolute neutrophil count) ≥1.5 x 10^9/L Hemoglobin ≥9 g/dL Platelets ≥100 x 10^9/L
  • Hepatic:
  • Albumin ≥2.5 g/dL Serum bilirubin ≤1.5 x upper limit of normal (ULN)
  • 2.5 x ULN if patient has Gilbert's syndrome aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 x ULN without liver metastases
  • 5 x ULN if documented liver metastases

Who cannot join

  • Pregnant or lactating females at anytime during the study
  • Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. In addition, subjects with ulcerative colitis are also excluded
  • History of other malignancy. Subjects who have been disease-free for 5 years or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible
  • Concurrent disease or condition that would make the subject inappropriate for study participation, or any serious medical disorder that would interfere with the subject's safety
  • Unresolved or unstable serious toxicity from prior administration of another investigational drug
  • Active or uncontrolled infection
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  • Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent
  • Known history of uncontrolled or symptomatic angina, arrhythmia or congestive heart failure
  • No prior anti-ErbB1/ErbB2 inhibitor for breast cancer other than trastuzumab
  • Known history or clinical evidence of leptomeningeal carcinomatosis
  • Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, or tumor embolization) other than capecitabine
  • Bisphosphonates for the treatment of bone metastases should not be initiated following the first dose of randomized therapy. Prophylactic use of bisphosphonates in subjects without bone disease is not permitted, except for prevention of osteoporosis
  • Concurrent treatment with an investigational agent or participation in another clinical trial
  • Use of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study medication
  • Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to GW572016 or excipients of GW572016
  • Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to capecitabine, fluorouracil or any excipients
  • Known dihydropyrimidine dehydrogenase (DPD) deficiency

About this study

Official title: A Phase III, Randomized, Open-label, Multicenter Study Comparing GW572016 and Capecitabine (XELODA) Versus Capecitabine in Women With Refractory Advanced or Metastatic Breast Cancer

This study was designed to compare the efficacy and safety of an oral dual tyrosine kinase inhibitor in combination with capecitabine versus capecitabine alone in women with locally advanced or metastatic breast cancer that has not responded to previous therapy.

Conditions
Breast Cancer
Being tested
capecitabine, lapatinib (GW572016)
Keywords
XELODA, Metastatic, Breast Cancer, Advanced, HERCEPTIN
Medical subject headings
Breast Neoplasms, Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • capecitabineDrug

    Capecitabine daily dose divided and given twice daily orally, for 14 days, every 21 days. The capecitabine starting dose for the monotherapy arm was 2500 mg/m2 and for the combination arm was 2000 mg/m2.

  • lapatinib (GW572016)Drug

    Lapatinib 1250 mg orally once daily

Study groups in NCT00078572
Study groupRoleWhat they receive
capecitabine aloneActive comparatorCapecitabine daily dose divided and given twice daily orally, for 14 days, every 21 days. The capecitabine starting dose for the monotherapy arm was 2500 mg/m2. Randomization is 1:1.
Receives: Drug: capecitabine
CombinationExperimentalLapatinib 1250 mg once daily plus capecitbine daily dose divided and given twice daily orally, for 14 days, every 21 days. The capecitabine starting dose for the combination arm was 2000 mg/m2.
Receives: Drug: capecitabine; Drug: lapatinib (GW572016)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Time to progression

    Measured: randomization to time of progression or death due to breast cancer

Secondary outcomes (9)

  1. Overall survival

    Measured: from randomization until death due to any cause

  2. progression-free survival

    Measured: time from randomization until first documented sign of disease progression

  3. 6-month progression-free survival

    Measured: six months after the date of randomization

  4. overall tumor response rate (percentage of subjects achieving complete response (CR) or partial response (PR)

    Measured: response after randomization

  5. clinical benefit rate (percentage of subjects with CR or PR or stable disease [SD] for ≥6 months)

    Measured: response after randomization

  6. time to response

    Measured: from randomization until first documented sign of CR/ PR

  7. Quality of Life (QoL)

    Measured: duration of study

  8. Safety

    Measured: duration of study

  9. Biomarkers

    Measured: duration of study

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Mar 2004 (estimated)
  2. Study startMar 2004
  3. Primary completionApr 2006
  4. Study completionFeb 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
408 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00078572
Sponsor's protocol ID
100151
Status last verified
Dec 2010
First submitted
1 Mar 2004
Last updated
13 Dec 2010
Results posted
No
Data monitoring committee
Yes

Publications

  • Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, Jagiello-Gruszfeld A, Crown J, Chan A, Kaufman B, Skarlos D, Campone M, Davidson N, Berger M, Oliva C, Rubin SD, Stein S, Cameron D. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006 Dec 28;355(26):2733-43. doi: 10.1056/NEJMoa064320.

    PubMed 17192538

  • Cameron D, Casey M, Press M, Lindquist D, Pienkowski T, Romieu CG, Chan S, Jagiello-Gruszfeld A, Kaufman B, Crown J, Chan A, Campone M, Viens P, Davidson N, Gorbounova V, Raats JI, Skarlos D, Newstat B, Roychowdhury D, Paoletti P, Oliva C, Rubin S, Stein S, Geyer CE. A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses. Breast Cancer Res Treat. 2008 Dec;112(3):533-43. doi: 10.1007/s10549-007-9885-0. Epub 2008 Jan 11.

    PubMed 18188694

  • Cameron D, Casey M, Oliva C, Newstat B, Imwalle B, Geyer CE. Lapatinib plus capecitabine in women with HER-2-positive advanced breast cancer: final survival analysis of a phase III randomized trial. Oncologist. 2010;15(9):924-34. doi: 10.1634/theoncologist.2009-0181. Epub 2010 Aug 24.

    PubMed 20736298

  • Labonte MJ, Wilson PM, Yang D, Zhang W, Ladner RD, Ning Y, Gerger A, Bohanes PO, Benhaim L, El-Khoueiry R, El-Khoueiry A, Lenz HJ. The Cyclin D1 (CCND1) A870G polymorphism predicts clinical outcome to lapatinib and capecitabine in HER2-positive metastatic breast cancer. Ann Oncol. 2012 Jun;23(6):1455-64. doi: 10.1093/annonc/mdr445. Epub 2011 Oct 11.

    PubMed 21989330

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing capecitabine and lapatinib (GW572016) in people with Breast Cancer, run by GlaxoSmithKline.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 32 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Dec 2010. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time to progression (time frame: randomization to time of progression or death due to breast cancer). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00078572, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Dec 2010.

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