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Neoplasms, BreastPhase 2NCT00356811

Lapatinib Combined With Paclitaxel For Patients With First-Line ErbB2-Amplified Metastatic Breast Cancer

A Phase 2 study testing Lapatinib oral tablets and Paclitaxel infusion in people with Neoplasms, Breast, run by GlaxoSmithKline at 13 sites in 4 countries.

Completed

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

Official record
Search all trials

Trial summary

This study investigates the safety and efficacy of oral lapatinib in combination with an approved medication, paclitaxel, for patients with ErbB2 metastatic breast cancer. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Neoplasms, Breast
What is being tested?
Lapatinib oral tablets and Paclitaxel infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
57 participants
Where
13 sitesin 4 countries
Study dates
May 2006to Dec 2013
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • A subject will be eligible for inclusion in this study only if all of the following criteria apply:
  • Signed informed consent.
  • Only females ≥18 years of age will be recruited:
  • Non-child-bearing potential (i.e., women with functioning ovaries who have a current documented tubal ligation or hysterectomy, or women who are postmenopausal); or
  • Child-bearing potential (i.e., women with functioning ovaries and no documented impairment of oviductal or uterine function that would cause sterility). This category includes women with oligomenorrhoea (severe), women who are perimenopausal and young women who have begun to menstruate. These subjects must provide a negative serum pregnancy test at Screening and agree to one of the following:
  • Complete abstinence from intercourse from 2 weeks prior to administration of the first dose of study medication until 28 days after the final dose of study medication; or
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  • Consistent and correct use of one of the following acceptable methods of birth control:
  • Male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject.
  • Implants of levonorgestrel.
  • Injectable progestogen.
  • Any intrauterine device (IUD) with a documented failure rate of less than 1% per year.
  • Oral contraceptives (either combined or progestogen only).
  • Barrier methods, including diaphragm or condom with a spermicide.
  • Subjects must have histologically confirmed invasive breast cancer with stage IVdisease;
  • Where the disease is restricted to a solitary lesion, the neoplastic nature of the lesion should be confirmed by cytology or histology.
  • Subjects whose disease is ER+ and/or PR+ or unknown status will only be included in the study if they meet the following criteria:
  • They have symptomatic visceral disease that requires chemotherapy (e.g., patients with liver or lung metastases).
  • The disease is considered by the Investigator to be progressing rapidly or lifethreatening.
  • Subjects who have received endocrine therapy and who are no longer benefiting from this therapy.
  • Documented amplification of ErbB2 defined by FISH in primary or metastatic tumor tissue. Results of FISH testing at local laboratories are acceptable, however, tissue sample must still be sent to Central laboratory where results will be repeated but not used for eligibility criterion.
  • If a taxane had been administered in the neoadjuvant or adjuvant setting, progression must have occurred ≥12 months after completion of this treatment.
  • Measurable lesion(s) according to RECIST (Response Evaluation Criteria in Solid Tumors) criteria [Stephens, 2004; Therasse, 2000].
  • Radiotherapy prior to initiation of study medication is allowed to a limited area (e.g., palliative treatment for painful bone metastases), if it is not the sole site of disease. Subject must have completed radiation treatment and recovered from all acute radiation treatment-related toxicities, in particular bone marrow suppression.
  • Bisphosphonate therapy for bone metastases is allowed however; treatment must be initiated prior to the first dose of study medication. Prophylactic use of bisphosphonates in subjects without bone disease, except for the treatment of osteoporosis, is not permitted.
  • Subjects with stable central nervous system (CNS) metastases (stable for at least 3 months) as confirmed by computerized tomography (CT)/magnetic resonance imaging (MRI)) or leptomeningeal involvement are eligible only if they are not taking oral steroids or enzyme-inducing anticonvulsants.
  • Subjects must have a cardiac ejection fraction within institutional range of normal as measured by echocardiogram (or multigated acquisition (MUGA) scan if an echocardiogram cannot be performed or is inconclusive). Subjects with known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure are not eligible.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 - 1.
  • Considered by the Investigator to have a life expectancy of at least 3 months.
  • Able to swallow and retain oral medication.
  • Subjects must have new or archived tumor tissue available for analysis.
  • Subjects must complete all screening assessments as outlined in the protocol.
  • Subject must have adequate organ function as defined in Table 1.
  • Table 1 Baseline Laboratory Values for Adequate Organ Function SYSTEM LABORATORY VALUES
  • Haematologic
  • Absolute neutrophil count ≥1.5 × 10^9/L Haemoglobin ≥9 g/dL Platelets ≥100 × 10^9/L
  • Hepatic
  • Albumin ≥2.5 g/dL Serum bilirubin
  • 1.25 x ULN AST and ALT ≤3 × ULN without liver metastases
  • 5 × ULN with documented liver metastases
  • Renal
  • Serum Creatinine1 ≤2.0 mg/dL
  • OR - Calculate Creatinine Clearance1 ≥40 mL/min
  • Calculated by the Cockcroft and Gault Method. ALT = alanine aminotransferase; AST = aspartate aminotransferase

Who cannot join

  • A subject will not be eligible for inclusion in this study if any of the following criteria apply:
  • Pregnant or lactating females.
  • Received prior chemotherapy, hormonal therapy, immunotherapy, biologic therapy for metastatic disease.
  • Prior therapy with ErbB1 and/or ErbB2 inhibitors.
  • Concurrent anti-cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy) while taking study medication.
  • Unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or of prior cancer treatment.
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  • Peripheral neuropathy of grade 2 or greater.
  • Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Subjects with ulcerative colitis are also excluded.
  • History of other malignancy. However, 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.
  • Active or uncontrolled infection.
  • 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, arrhythmias, or congestive heart failure.
  • Concurrent treatment with an investigational agent or participation in another clinical trial involving investigational agents.
  • Used an investigational drug within 30 days or five half-lives, whichever is longer, preceding the first dose of investigational treatment.
  • The subject has a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to lapatinib or excipients and those related to paclitaxel or excipients.

Trial locations and contacts

13 sites in 4 countries.

13 sites in 4 countries

Russia5 sites
  • GSK Investigational Site

    Moscow, 115 478

  • GSK Investigational Site

    Moscow, 117997

  • GSK Investigational Site

    Moscow, 129 128

  • GSK Investigational Site

    Saint Petersburg, 197022

  • GSK Investigational Site

    Saint Petersburg, 197758

Other trials in Russia

Poland4 sites
  • GSK Investigational Site

    Krakow, 31-115

  • GSK Investigational Site

    Olsztyn, 10-228

  • GSK Investigational Site

    Olsztyn, 10-699

  • GSK Investigational Site

    Warsaw, 02-781

Other trials in Poland

Latvia3 sites
  • GSK Investigational Site

    Liepāja, LV3401

  • GSK Investigational Site

    Riga, LV 1002

  • GSK Investigational Site

    Riga, LV 1079

Other trials in Latvia

Romania1 site
  • GSK Investigational Site

    Bucharest, 022328

Other trials in Romania

About this study

Official title: An Open-label, Single-arm, Multi-centre, Phase II Study of Oral Lapatinib in Combination With Paclitaxel as First-line Treatment for ErbB2-amplified Metastatic Breast Cancer Patients

This study investigates the safety and efficacy of oral lapatinib in combination with an approved medication, paclitaxel, for patients with ErbB2 metastatic breast cancer.

Being tested
Lapatinib oral tablets, Paclitaxel infusion
Keywords
Lapatinib, Metastatic breast cancer, Paclitaxel, ErbB2-amplification, GW572016
Medical subject headings
Breast Neoplasms

What participants receive

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

  • Lapatinib oral tabletsDrug

    Also called Tykerb/ Tyverb

    Lapatinib will be given as tablets contain 410 mg of lapatinib ditosylate monohydrate, equivalent to 250 mg lapatinib free base per tablet. Subjects will be given a 4 week supply of lapatinib tables and instructed to take 6 tablets daily (1500 mg daily dose) orally at the same time each day. Subjects will receive a daily dose of lapatinib until disease progression or withdrawal from study treatment due to unacceptable toxicity or withdrawal of consent.

  • Paclitaxel infusionDrug

    Also called Taxol

    Subjects will receive weekly paclitaxel (80 mg/m2 IV for 3 weeks in a 4 week cycle). Subjects will be treated with paclitaxel for at least 6 months, and may continue on paclitaxel at the discretion of the Investigator, or discontinued sooner if the subject has disease progression, an unacceptable toxicity or withdraws consent.

Study groups in NCT00356811
Study groupRoleWhat they receive
Single armExperimentalSubjects will receive a daily dose of lapatinib until disease progression or withdrawal from study treatment due to unacceptable toxicity or withdrawal of consent. Subjects will be treated with paclitaxel for at least 6 months, and may continue on paclitaxel at the discretion of the Investigator, or discontinued sooner if the subject has disease progression, an unacceptable toxicity or withdraws consent.
Receives: Drug: Lapatinib oral tablets; Drug: Paclitaxel infusion

What is being measured

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

  1. Number of Participants With a Best Overall Response (OR) of Confirmed Complete Response (CR) or Partial Response (PR), as Assessed by the Independent Review Committee (IRC)

    OR is defined as the number of participants achieving either a CR or PR, per Response Evaulation Criteria in Solid Tumors (RECIST). The best OR is defined as the best response recorded from the start of treatment until progressive disease (PD)/recurrence. CR is defined as the disappearance of all target lesions (TLs) and non-TLs. PR is defined as at least a 30% decrease in the sum of the longest diameters (LD) of TLs, taking as a reference the Baseline sum LD and no PD, or complete resolution of TLs and the persistence of one or more non-TL(s), as assessed by the IRC. PD is defined as at least a 20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-TLs. Responses were confirmed at subsequent assessments made >=28 days after the original response. Participants with an unknown or missing response are treated as non-responders.

    Measured: From the first dose of study medication to the first documented evidence of a confirmed CR or PR (up to Week 86)

Secondary outcomes (9)
  1. Number of Participants With a Best Overall Response (OR) of Confirmed Complete Response (CR) or Partial Response (PR), as Assessed by the Investigator

    OR is defined as the number of participants achieving either a CR or PR, per RECIST. The best OR is defined as the best response recorded from the start of treatment until progressive disease (PD)/recurrence. CR is defined as the disappearance of all target lesions (TLs) and non-TLs. PR is defined as at least a 30% decrease in the sum of the longest diameters (LD) of TLs, taking as a reference the Baseline sum LD and no PD, or complete resolution of TLs and the persistence of one or more non-TL(s), as assessed by the Investigator. PD is defined as at least a 20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-TLs. Responses were confirmed at subsequent assessments made >=28 days after the original response. Participants with an unknown or missing response are treated as non-responders.

    Measured: From the first dose of study medication to the first documented evidence of a confirmed CR or PR (up to Week 86)

  2. Duration of Response (DoR), as Assessed by the IRC

    DoR is defined for the subset of participants who had a confirmed CR (disappearance of all TLs and non-TLs) or PR (>=30% decrease in the sum of the LD of TLs, taking as a reference the Baseline sum LD and no PD, or complete resolution of TLs and the persistence of one or more non-TL[s]) as the time from the first documented evidence of a CR or PR until the first documentation of radiological PD or death due to breast cancer, if sooner. PD is defined as a >=20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-TLs. For participants who did not progress or die, DoR was censored on the date of the last radiological scan. If a participant had only a Baseline visit or did not have a date of a radiological scan that was later than the date of initiation of anti-cancer therapy, DoR was censored at the start date of treatment.

    Measured: From the first documented evidence of a PR or CR until the earlier of the date of disease progression or the date of death due to breast cancer (up to Week 86)

  3. Duration of Response (DoR), as Assessed by the Investigator

    DoR is defined for the subset of participants who had a confirmed CR (disappearance of all TLs and non-TLs) or PR (>=30% decrease in the sum of the LD of TLs, taking as a reference the Baseline sum LD and no PD, or complete resolution of TLs and the persistence of one or more non-TL[s]) as the time from the first documented evidence of a CR or PR until the first documentation of radiological PD or death due to breast cancer, if sooner. PD is defined as a >=20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-TLs. For participants who did not progress or die, DoR was censored on the date of the last radiological scan. If a participant had only a Baseline visit or did not have a date of a radiological scan that was later than the date of initiation of anti-cancer therapy, DoR was censored at the start date of treatment.

    Measured: From the first documented evidence of a PR or CR until the earlier of the date of disease progression or the date of death due to breast cancer (up to Week 86)

  4. Time to Response, as Assessed by the IRC

    Time to response is defined as the time from randomization until the first documented evidence of a PR or CR (whichever status is recorded first). Analysis was based on responses confirmed at a repeat assessment made at least 4 weeks after the initial response, with the time to response taken as the first time the response was observed, not the confirmation assessment. Participants who withdraw with no tumor response were censored at the date of withdrawal from the study. CR is defined as the disappearance of all TLs and non-TLs. PR is defined as at least a 30% decrease in the sum of the LD of TLs, taking as a reference the Baseline sum LD and no PD, or complete resolution of TLs and the persistence of one or more non-TL(s). PD is defined as at least a 20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-TLs.

    Measured: From randomization until the first documented evidence of a PR or CR (up to Week 86)

  5. Time to Response, as Assessed by the Investigator

    Time to response is defined as the time from randomization until the first documented evidence of a PR or CR (whichever status is recorded first). Analysis was based on responses confirmed at a repeat assessment made at least 4 weeks after the initial response, with the time to response taken as the first time the response was observed, not the confirmation assessment. Participants who withdraw with no tumor response were censored at the date of withdrawal from the study. CR is defined as the disappearance of all TLs and non-TLs. PR is defined as at least a 30% decrease in the sum of the LD of TLs, taking as a reference the Baseline sum LD and no PD, or complete resolution of TLs and the persistence of one or more non-TL(s). PD is defined as at least a 20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-TLs.

    Measured: From randomization until the first documented evidence of a PR or CR (up to Week 86)

  6. Time to Progression, as Assessed by the IRC and the Investigator

    Time to progression is defined as the interval between the start date of treatment and the date of radiological disease progression or death due to breast cancer, whichever occurs first. Participents who did not progress or die were censored on the date of their last radiological assessment preceding the start of any additional anti-cancer therapy. PD is defined as at least a 20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-TLs. Responses were confirmed at a subsequent assessment made no less than 28 days after the original response.

    Measured: From the start date of treatment until the date of radiological disease progression or the date of death due to breast cancer (up to Week 86)

  7. Progression-free Survival, as Assessed by the IRC and the Investigator

    Progression-free survival is defined as the interval between the start date of treatment and the date of radiological disease progression or death due to any cause, whichever occurs first. Participants who did not progress in their disease were censored on the date of their last radiological assessment preceding the start of any additional anti-cancer therapy. PD is defined as at least a 20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-TLs. Responses were confirmed at a subsequent assessment made no less than 28 days after the original response.

    Measured: From the start date of treatment until the date of radiological disease progression or death due to any cause, whichever occurs first (up to Week 86)

  8. Overall Survival

    Overall survival is defined as the interval between the date of treatment start and the date of death due to any cause. For participants who did not die, follow-up was censored as the date of last contact. For participants who did not die, follow-up was censored at the date of last contact.

    Measured: From the date of the first dose until the date of death due to any cause (up to Week 86)

  9. Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)

    An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect. Medical or scientific judgment was exercised in deciding whether reporting was appropriate in other situations.

    Measured: From the start of study medication until 28 days after the last dose (up to Study Week 381)

Timeline

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

  1. First posted26 Jul 2006 (estimated)
  2. Study startMay 2006
  3. Primary completionMar 2008
  4. Study completionDec 2013

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
57 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00356811
Sponsor's protocol ID
EGF105764
Status last verified
May 2014
First submitted
25 Jul 2006
Last updated
21 Jul 2014
Data monitoring committee
No

Publications

  • Jagiello-Gruszfeld A, Tjulandin Sergei S, Dobrovolskaya N et al, Lapatinib (L) with weekly paclitaxel (P) as first-line therapy for patients (pts) with HER2+ metastatic breast cancer (MBC). The 31st Annual San Antonio Breast Cancer Symposium; San Antonio TX: December 10-14 2008. Abstract 3145.

  • Jagiello-Gruszfeld A, Tjulandin S, Dobrovolskaya N, Manikhas A, Pienkowski T, DeSilvio M, Ridderheim M, Abbey R. A single-arm phase II trial of first-line paclitaxel in combination with lapatinib in HER2-overexpressing metastatic breast cancer. Oncology. 2010;79(1-2):129-35. doi: 10.1159/000318043. Epub 2010 Nov 22.

    PubMed 21088439

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Lapatinib oral tablets and Paclitaxel infusion in people with Neoplasms, Breast, run by GlaxoSmithKline at 13 sites in 4 countries.

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 43 inclusion and 16 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 21 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in Russia, Poland, Latvia, Romania. Whether a site is taking part right now should be confirmed with that site. See every site.

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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Jul 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Participants With a Best Overall Response (OR) of Confirmed Complete Response (CR) or Partial Response (PR), as Assessed by the Independent Review Committee (IRC) (time frame: From the first dose of study medication to the first documented evidence of a confirmed CR or PR (up to Week 86)). 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 NCT00356811, which also lists 2 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 21 Jul 2014.

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