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Metastatic Breast CancerPhase 2NCT00477464

Lapatinib in Combination With Capecitabine in Japanese Patients With Metastatic Breast Cancer

A Phase 2 study testing Lapatinib and capecitabine in people with Metastatic Breast Cancer and Neoplasms, Breast, run by GlaxoSmithKline at 15 sites in Japan.

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 is to evaluate the safety and efficacy of lapatinib taken together with capecitabine in Japanese patients. The study will proceed in two phases; the first phase(Part1) will lead to an evaluation of the mainly tolerability as well as PK parameters. Read more about this study

Who is it for?
Ages 20 years and older, women only
Conditions the study is for
Metastatic Breast Cancer, Neoplasms, Breast
What is being tested?
Lapatinib and capecitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
51 participants
Where
15 sitesJapan
Study dates
Jun 2007to Dec 2010
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 20 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subjects eligible for enrolment in the study must meet all of the following criteria:
  • Patients who have consent to this study participation and signed into Informed consent form.
  • Subjects must have histologically confirmed invasive breast cancer with stage IIIB, stage IIIC with T4 lesion, or stage IV disease.
  • Documentation of ErbB2 overexpression [IHC3+ or IHC2+ with FISH confirmation] is required based on local laboratory.
  • Subjects must have documented progressive advanced or metastatic breast cancer.
  • 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:
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  • Taxane containing regimen for at least 4 cycles or 2 cycles provided disease progression occurred while on taxane.
  • 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 alone or in combination with other chemotherapy for at least 6 weeks of standard doses in the adjuvant or advanced/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 CNS metastases (asymptomatic, and off systemic steroids and anticonvulsants for at least 3 months) are eligible.
  • Measurable disease according to modified RECIST (Response Evaluation Criteria in Solid Tumors) (see Section 6.2, Efficacy p.49).
  • Subjects must have archived tumor tissue available for biomarker assessment.
  • Female subjects must be ≥20
  • ECOG Performance Status of 0 or 1.
  • Life expectancy of ≥12 weeks.
  • 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 ECHO (or MUGA if ECHO is not available). If no institutional range is available, cardiac ejection fraction must be ≥50%.
  • Adequate hematologic value, hepatic and renal function as defined below. Hematologic ANC (absolute neutrophil count) ≥1.5×109/L Hemoglobin ≥9 g/dL Platelets ≥100× 109/L Hepatic Serum bilirubin ≤1.5×ULN
  • 2.5×ULN if subject has Gilbert's syndrome AST and ALT ≤5×ULN if documented liver metastases
  • 3×ULN without liver metastases Renal Serum creatinine Creatinine clearance* ≤50 mL/min
  • Calculated by the Cockcroft and Gault Method

Who cannot join

  • Subjects meeting any of the following criteria must not be enrolled in the study:
  • Pregnant or lactating females.
  • Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. In addition, subjects with ulcerative colitis are excluded.
  • History of other malignancy. Subjects who have been disease-free for at least 5 years or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.
  • Unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or of prior anticancer therapy.
  • 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 anticancer 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 study medication. Prophylactic use of bisphosphonate in subjects without bone disease is not permitted, except for prevention of osteoporosis.
  • Use of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study medication.
  • Participation in other studies or use of other investigational drugs during this study.
  • Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to lapatinib or excipients of lapatinib.
  • Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to capecitabine, fluorouracil or any excipients.
  • Known dihydropyrimidine dehydrogenase (DPD) deficiency.
  • Patients who an investigator judges ineligible to this study in consideration of patient's safety (e.g., complications).

Trial locations and contacts

15 sites in 1 country.

15 sites in 1 country

Japan15 sites

  • GSK Investigational Site

    Aichi, 464-8681

  • GSK Investigational Site

    Chiba, 277-8577

  • GSK Investigational Site

    Ehime, 791-0280

  • GSK Investigational Site

    Fukuoka, 811-1395

  • GSK Investigational Site

    Hokkaido, 003-0804

  • GSK Investigational Site

    Ibaraki, 305-8576

  • GSK Investigational Site

    Kagoshima, 892-0833

  • GSK Investigational Site

    Osaka, 540-0006

  • GSK Investigational Site

    Osaka, 553-0003

  • GSK Investigational Site

    Shizuoka, 411-8777

  • GSK Investigational Site

    Tochigi, 329-0498

  • GSK Investigational Site

    Tokyo, 104-0045

  • GSK Investigational Site

    Tokyo, 104-8560

  • GSK Investigational Site

    Tokyo, 113-8677

  • GSK Investigational Site

    Tokyo, 135-8550

Other trials in Japan

About this study

Official title: Clinical Evaluation of Lapatinib Administered With Capecitabine in Japanese Patients With ErbB2 Overexpressing Advanced or Metastatic Breast Cancer

This study is to evaluate the safety and efficacy of lapatinib taken together with capecitabine in Japanese patients. The study will proceed in two phases; the first phase(Part1) will lead to an evaluation of the mainly tolerability as well as PK parameters. If there are no major safety concerns in Part 1, the study will move into the second phase (Part 2) to further evaluate the safety and clinical activity.

Being tested
Lapatinib, capecitabine
Keywords
dual kinase inhibitor,, EGFR/ErbB1,, ErbB2-overexpressing,, GW572016,, advanced/metastatic breast cancer, Lapatinib,, HER-2/new,, pharmacokinetics
Medical subject headings
Breast Neoplasms

What participants receive

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

  • LapatinibDrug

    1250mg once daily

  • capecitabineDrug

    2000mg/m^2 twice daily (14 days out of 21 days)

Study groups in NCT00477464
Study groupRoleWhat they receive
Lapatinib+capecitabineExperimentalLapatinib 1250mg once daily +capecitabine 2000mg/m^2 twice daily (14 days out of 21 days)
Receives: Drug: Lapatinib; Drug: capecitabine

What is being measured

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

  1. Clinical Benefit Response (Independent Reviewer-assessed)

    CBR is defined as the percentage of participants receiving at least one dose of study medication who achieved a best overall response classified as a complete or partial (confirmed) tumor response or stable disease for at least 6 months (24 weeks). A "complete response" is defined as the disappearance of all target or non-target lesions, "partial response" and "disease progression" as at least a 30% decrease and at least a 20% increase, respectively, in the sum of the longest diameter of target lesions, and "stable disease" as neither "partial response" nor "disease progression."

    Measured: Baseline, every 6 weeks until Week 24 and then every 12 weeks until disease progression (up to Week 119)

Secondary outcomes (19)

  1. Time to Progression (Independent Reviewer-assessed)

    Time to progression is defined as the interval between the start of treatment and the earliest date of disease progression or death due to breast cancer, if sooner. Time to progression was calculated by using the Kaplan Meier estimate.

    Measured: Baseline, every 6 weeks until Week 24 and then every 12 weeks until disease progression or death due to breast cancer (up to Week 119)

  2. Progression-free Survival (PFS) (Independent Reviewer-assessed)

    PFS is defined as the interval between the start of treatment and the earliest date of disease progression or death of any cause, if sooner.

    Measured: Baseline, every 6 weeks until Week 24 and then every 12 weeks until disease progression or death (up to Week 119)

  3. 6-Month Progression-free Survival (Independent Reviewer-assessed)

    6-Month progression-free survival is defined as the percentage of participants surviving without progressive disease at 6 months (24 weeks) after the start of treatment. Progressive disease is defined as at least a 20% increase in the sum of the longest diameter of target lesions.

    Measured: Baseline and then every 6 weeks until Month 6 (Week 24)

  4. Objective Response (Independent Reviewer-assessed)

    Objective response is defined as the percentage of participants achieving a best overall response classified as a complete or partial (confirmed) tumor response. Complete response is defined as the disappearance of all target or non-target lesions, and partial response is defined as at least a 30% decrease in the sum of the longest diameter of target lesions.

    Measured: Baseline every 6 weeks until Week 24 and then every 12 weeks until disease progression or death (up to Week 119)

  5. Overall Survival (Independent Reviewer-assessed)

    Overall survival is defined as the time from the start of treatment until death regardless of cause. For participants who did not die, time to death was censored at the time of last confirmation of survival.

    Measured: Baseline and then followed every 4 weeks until death (up to Week 157.9) while on treatment. After treatment termination, followed every 12 weeks until death (up to Week 157.9)

  6. Time to Response (Independent Reviewer-assessed)

    Time to response is defined as the time from the start of treatment until the first documented evidence of complete response or partial response.

    Measured: Baseline, every 6 weeks until Week 24 and then every 12 weeks until disease progression or death (up to Week 119)

  7. Duration of Response (Independent Reviewer-assessed)

    For the subset of participants who showed a complete or partial response, duration of response is defined as the time from the first documented evidence of partial or complete tumor response until the first documented sign of disease progression or death due to breast cancer, if sooner.

    Measured: Baseline, every 6 weeks until Week 24 and then every 12 weeks until disease progression or death (up to Week 119)

  8. Maximum Plasma Concentration (Cmax) of Lapatinib

    Pharmacokinetic (PK) samples were collected at pre-dose, and at 1, 2, 3, 4 (plus or minus 15 minutes), 6, 8, 10, 12, and 24 hours (hr) (plus or minus 30 minutes) after dosing. Cmax is defined as the maximum concentration of lapatinib.

    Measured: Week 2

  9. Time to Maximum Plasma Concentration (Tmax) of Lapatinib

    PK samples were collected at pre-dose, and at 1, 2, 3, 4 (plus or minus 15 minutes), 6, 8, 10, 12, and 24 hr (plus or minus 30 minutes) after dosing. Tmax is defined as the time to peak concentration from initiation of lapatinib dosing.

    Measured: Week 2

  10. Terminal Elimination Half-life (t1/2) of Lapatinib

    Terminal elimination half-life is defined as the duration until observation of half of the maximum concentration. PK samples were collected at pre-dose, and at 1, 2, 3, 4 (plus or minus 15 minutes), 6, 8, 10, 12, and 24 hr (plus or minus 30 minutes) after dosing.

    Measured: Week 2

  11. Area Under the Plasma Concentration-time Curve Within the Dosing Interval AUC0-tau of Lapatinib

    PK samples were collected at pre-dose, and at 1, 2, 3, 4 (plus or minus 15 minutes), 6, 8, 10, 12, and 24 hr (plus or minus 30 minutes) after dosing. AUC is defined as the area under the concentration-time curve from 0 to last quantifiable concentration (AUC 0-tau). AUC is a measure of exposure.

    Measured: Week 2

  12. Area Under the Plasma Concentration-time Curve From Zero to 24 Hours AUC0-24 of Lapatinib

    PK samples were collected at pre-dose, and at 1, 2, 3, 4 (plus or minus 15 minutes), 6, 8, 10, 12, and 24 hr (plus or minus 30 minutes) after dosing. AUC is defined as the area under the concentration-time curve from 0 to 24 hour after dosing (AUC 0-24). AUC is a measure of exposure.

    Measured: Week 2

  13. Cmax of Capecitabine, 5'-Fluorouracil (5-FU), and Alpha-fluoro-beta-alanine (FBAL)

    PK samples were collected at pre-dose, and at 0.5 (plus or minus 5 minutes), 1, 2, 3, 4 (plus or minus 15 minutes), 6, 8, and 10 hr (plus or minus 30 minutes) after dosing. Cmax is defined as the maximum concentration of drug. 5-FU and FBAL were evaluated because of the following reasons: (1) capecitabine is an orally administered fluoropyrimidine carbamate selectively activated to fluorouracil (5-FU) in tumors; (2) FBAL is an inactive major metabolite of capecitabine, and metabolites of capecitabine are excreted mainly in urine.

    Measured: Week 2

  14. Tmax of Capecitabine, 5'-Fluorouracil (5-FU), and Alpha-fluoro-beta-alanine (FBAL)

    PK samples were collected at pre-dose, and at 0.5 (plus or minus 5 minutes), 1, 2, 3, 4 (plus or minus 15 minutes), 6, 8, and 10 hr (plus or minus 30 minutes) after dosing. Tmax is defined as the time to peak concentration from initiation of dosing. 5-FU and FBAL were evaluated because of the following reasons: (1) capecitabine is an orally administered fluoropyrimidine carbamate selectively activated to fluorouracil (5-FU) in tumors; (2) FBAL is an inactive major metabolite of capecitabine, and metabolites of capecitabine are excreted mainly in urine.

    Measured: Week 2

  15. t1/2 of Capecitabine, 5'-Fluorouracil (5-FU), and Alpha-fluoro-beta-alanine (FBAL)

    Terminal elimination half-life is defined as the duration until observation of half of the maximum concentration. PK samples were collected at pre-dose, and at 0.5 (plus or minus 5 minutes), 1, 2, 3, 4 (plus or minus 15 minutes), 6, 8, and 10 hr (plus or minus 30 minutes) after dosing. 5-FU and FBAL were evaluated because of the following reasons: (1) capecitabine is an orally administered fluoropyrimidine carbamate selectively activated to fluorouracil (5-FU) in tumors; (2) FBAL is an inactive major metabolite of capecitabine, and metabolites of capecitabine are excreted mainly in urine.

    Measured: Week 2

  16. AUC0-tau of Capecitabine, 5'-Fluorouracil (5-FU), and Alpha-fluoro-beta-alanine (FBAL)

    PK samples were collected at pre-dose, and at 0.5 (plus or minus 5 minutes), 1, 2, 3, 4 (plus or minus 15 minutes), 6, 8, and 10 hr (plus or minus 30 minutes) after dosing. AUC is defined as the area under the concentration-time curve from 0 to last quantifiable concentration (AUC 0-tau). 5-FU and FBAL were evaluated because of the following reasons: (1) capecitabine is an orally administered fluoropyrimidine carbamate selectively activated to fluorouracil (5-FU) in tumors; (2) FBAL is an inactive major metabolite of capecitabine, and metabolites of capecitabine are excreted mainly in urine.

    Measured: Week 2

  17. Area Under the Plasma Concentration-time Curve From Zero to 12 Hours (AUC0-12) of Capecitabine, 5'-Fluorouracil (5-FU), and Alpha-fluoro-beta-alanine (FBAL)

    PK samples were collected at pre-dose, and at 0.5 (plus or minus 5 minutes), 1, 2, 3, 4 (plus or minus 15 minutes), 6, 8, and 10 hr (plus or minus 30 minutes) after dosing. AUC is defined as the area under the concentration-time curve from 0 to 12 hours after dosing (AUC 0-12). 5-FU and FBAL were evaluated because of the following reasons: (1) capecitabine is an orally administered fluoropyrimidine carbamate selectively activated to fluorouracil (5-FU) in tumors; (2) FBAL is an inactive major metabolite of capecitabine, and metabolites of capecitabine are excreted mainly in urine.

    Measured: Week 2

  18. Trough Concentration of Lapatinib

    PK samples were collected at pre-dose on Day 14 and Day 21 (minus 2 days). Trough concentration is defined as the minimum serum concentration at steady state after a repeated dose of lapatinib.

    Measured: Week 2

  19. Trough Concentration of Capecitabine, 5-FU, and FBAL

    PK samples were collected at pre-dose on Day 14 (minus 2 days). Trough concentration is defined as the minimum serum concentration at steady state after a repeated dose. 5-FU and FBAL were evaluated because of the following reasons: (1) capecitabine is an orally administered fluoropyrimidine carbamate selectively activated to fluorouracil (5-FU) in tumors; (2) FBAL is an inactive major metabolite of capecitabine, and metabolites of capecitabine are excreted mainly in urine.

    Measured: Week 2

Timeline

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

  1. First posted23 May 2007 (estimated)
  2. Study startJun 2007
  3. Primary completionDec 2010
  4. Study completionDec 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 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
51 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00477464
Sponsor's protocol ID
109749
Status last verified
Sep 2011
First submitted
22 May 2007
Last updated
17 Sep 2018
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Lapatinib and capecitabine in people with Metastatic Breast Cancer and Neoplasms, Breast, run by GlaxoSmithKline at 15 sites in Japan.

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 25 inclusion and 18 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 17 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in Japan. 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 5 Sep 2011). 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?

Clinical Benefit Response (Independent Reviewer-assessed) (time frame: Baseline, every 6 weeks until Week 24 and then every 12 weeks until disease progression (up to Week 119)). 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 NCT00477464.

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 17 Sep 2018.

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