Lapatinib +Capecitabine Treatment for Advanced Metastatic Breast Cancer in Women From China

An Open-Label Multicenter Study Administering Lapatinib and Capecitabine (Xeloda) in Women With Advanced or Metastatic Breast Cancer

Local study in China and Hong Kong to evaluate safety and efficacy in lapatinib + capecitabine in women with Human epidermal growth factor receptor 2 (HER2) positive advanced or metastatic breast cancer.

Study Overview

• Status: Terminated
• Conditions: Neoplasms, Breast
• Intervention / Treatment: Drug: lapatinib; Drug: capecitabine

Detailed Description

The Primary objective of the study was to evaluate the overall clinical benefit response (CBR) rate.

This was a single arm, open-label, multi-center study of lapatinib plus capecitabine in women from mainland China and Hong Kong who had advanced or metastatic breast cancer that progressed on prior chemotherapies with or without trastuzumab.

Participants received study treatment until disease progression, unacceptable toxicity, or withdrawal for any other reasons.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100021
    • Novartis Investigative Site
  • Beijing, China, 100071
    • Novartis Investigative Site
  • Shanghai, China, 200032
    • Novartis Investigative Site
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Novartis Investigative Site
    • Guangzhou, Guangdong, China, 510515
      • Novartis Investigative Site
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Novartis Investigative Site
  • Jiangsu
    • Nanjing, Jiangsu, China, 210009
      • Novartis Investigative Site
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310006
      • Novartis Investigative Site
    • Hangzhou, Zhejiang, China, 310022
      • Novartis Investigative Site
• Hong Kong
  • Hong Kong, Hong Kong
    • Novartis Investigative Site
  • Shatin, Hong Kong
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Signed informed consent;
• Female ≥18 years;

• Pathology that has histologically confirmed invasive breast cancer with stage IIIb/c or stage IV disease;

  • If recurrent disease is restricted to a solitary lesion, its neoplastic nature should be confirmed by cytology or histology.

• Documented overexpression of Her2 (ErbB2) of IHC 3+ or FISH positive, in primary or metastatic tumor tissue is required for enrollment into the study; by local testing or central laboratory testing determined by country of residence. NB. Approximately, 51 subjects will be enrolled in a single stage design to test for efficacy in women from China and Hong Kong. Due to the fact that trastuzumab is not commonly prescribed in China and Hong Kong, the current study allows up to 40% of subjects who are trastuzumab naïve to be enrolled.

• Prior therapies must include at minimum a taxane and/or anthracycline and may include trastuzumab if available; other prior regimens are not limited except capecitabine and Erbb2 inhibitors other than trastuzumab. Chemo regimen requirements are as follows:

  • Taxane containing regimen for at least 4 cycles or <4 cycles provided disease progression or treatment limiting toxicity occurred while on taxane
  • Anthracycline containing regimen for at least 4 cycles or <4 cycles provided disease progression or treatment limiting toxicity occurred while on anthracycline
  • Taxanes and Anthracyclines may have been administered concurrently or separately
  • Prior treatment may have contained trastuzumab alone or in combination with other chemotherapy in the adjuvant, locally advanced or metastatic setting and patient must have failed the treatment
  • Prior treatment with capecitabine is not permitted unless 6 months have elapsed since the last dose of capecitabine and the subject is free of any capecitabine related toxicity
  • Prior therapy with an ErbB1 and/or ErbB2 inhibitor, other than trastuzumab is not permitted
  • Other prior chemo-regimens not listed above are unlimited.

• For those subjects whose disease is ER+ and/or PR+ one of following criteria should be met.

  • Subjects who received hormonal therapy and are no longer benefiting from this therapy and the hormonal treatment must have been stopped before the first dose of investigational treatment
  • Subjects with visceral disease that requires chemotherapy (eg., subjects with liver or lung metastases)
  • Rapidly progressing or life threatening disease, as determined by the investigator
• Subjects with stable CNS metastases (asymptomatic and off systemic steroids and anticonvulsants for at least 3 months) are eligible
• Measurable lesion(s) according to RECIST (Response Evaluation Criteria in Solid Tumors);
• Radiotherapy as palliative treatment for painful metastatic disease is permitted but must have been stopped within 2 weeks prior to initiation of any investigational treatment. All subjects must have recovered from all radiotherapy related toxicities prior to initiation of any investigational treatment. The site of radiotherapy must not be used as a site of measurable disease;
• Cardiac ejection fraction within institutional range of normal as measured by echocardiogram. MUGA scans will be accepted in cases where an echocardiogram cannot be performed or is inconclusive;
• ECOG Performance Status of 0 to 1;
• Life expectancy of ≥ 12 weeks;
• Able to swallow and retain oral medication;
• Women with potential to have children must be willing to practice acceptable methods of birth control during the study;
• Willing to complete all screening assessments as outlined in the protocol;
• Adequate organ function as defined by the Table of Baseline Laboratory Values

Exclusion Criteria:

• Pregnant or lactating females at anytime during the study
• Subjects with only non-measurable metastatic sites of disease per RECIST, (e.g. bone metastases, pleural effusion, or ascites, etc.);
• Planned concurrent anti-cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy) while taking investigational treatment;
• Unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or of prior cancer treatment;
• 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;
• Uncontrolled infection;
• Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: lapatinib in combination with capecitabine; daily oral lapatinib (1250 mg/day) in combination with capecitabine (2000mg/m2/day on days1-14 every 21 days)	Drug: lapatinib; Lapatinib ditosylate monohydrate tablets, 250 mg, are oval, biconvex, orange, film-coated tablets taken orally.; Other Names: LAP016, GW572016; Drug: capecitabine; Capecitabine is supplied as a biconvex, oblong, light peach and peach colored, film-coated tablets for oral administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Benefit Rate (CBR)	CBR is defined by the percentage of participants achieving either a confirmed tumor response of complete response (CR) or partial response (PR) or stable disease (SD) for at least 24 weeks. Response Criteria in Solid Tumors (RECIST) is a system for measuring tumor shrinkage or progression in terms of the longest dimensions of the tumor on imaging scans such as computerized tomography (CT). A "partial response" requires a decrease of 30% or more, "complete response" requires all target lesions disappear, "Progression" requires an increase of at least 20%, and "Stable disease" falls in between these two. All responses have a repeat assessment to confirm the response.	Baseline; every 6 weeks for the first 36 weeks and then every 12 weeks until disease progression. The maximum time participants were followed was approx. 90 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	PFS is defined as the time from first dose date until the date of disease progression or death due to any reason, whichever occurs first.	Baseline; every 6 weeks for the first 36 weeks and then every 12 weeks until disease progression. The maximum time participants were followed was 90.38 months.
Six Months Progression-Free Survival	Six Months Progression-Free Survival is defined as the percentage of surviving participants who are progression-free longer than six months (greather than 180 days) after the first start date of study treatment.	at Baseline and every 6 weeks for the first 36 weeks and then every 12 weeks until disease progression. The maximum time participants were followed up to 90.38 months, with 6 months PFS reported.
Time to Response (TTR)	Time to response is defined as the time from first dose date until first documentation of disease response. TTR only applied to participants for whom best overall response was complete response (CR), partial response (PR) or stable disease (SD). Participants who had not had a partial response, complete response or stable disease at the cut-off date for this endpoint analysis were censored for time to response.	Baseline; every 6 weeks for the first 36 weeks and then every 12 weeks until disease progression. The maximum time participants were followed was approx. 14.78 months
Duration of Response (DOR)	Duration of response (complete response, partial response or stable disease) is defined as the time of first documentation of disease response until the date of disease progression or death due to breast cancer, whichever occurs first. DOR only applied to participants for whom best overall response was complete response (CR), partial response (PR) or stable disease (SD). Participants who had not had a partial response, complete response or stable disease at the cut-off date for this endpoint analysis were censored for duration of response.	Baseline; every 6 weeks for the first 36 weeks and then every 12 weeks until disease progression. The maximum time participants were followed was 88.80 months.
Number of Participants With Central Nervous System (CNS) as First Site of Relapse	Number of participants who had Central Nervous System metastasis as the first site of relapse. CT, Magnetic Resonance Imaging, etc. were used for the assessment.	Baseline; every 6 weeks for the first 36 weeks and then every 12 weeks until disease progression. The maximum time participants were followed was 90 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Xu BH, Jiang ZF, Chua D, Shao ZM, Luo RC, Wang XJ, Liu DG, Yeo W, Yu SY, Newstat B, Preston A, Martin AM, Chi HD, Wang L. Lapatinib plus capecitabine in treating HER2-positive advanced breast cancer: efficacy, safety, and biomarker results from Chinese patients. Chin J Cancer. 2011 May;30(5):327-35. doi: 10.5732/cjc.010.10507.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 18, 2007
• Primary Completion (ACTUAL): December 2, 2015
• Study Completion (ACTUAL): July 1, 2020

Study Registration Dates

• First Submitted: July 26, 2007
• First Submitted That Met QC Criteria: July 26, 2007
• First Posted (ESTIMATE): July 27, 2007

Study Record Updates

• Last Update Posted (ACTUAL): September 21, 2021
• Last Update Submitted That Met QC Criteria: August 26, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Capecitabine; breast cancer; lapatinib; HER2 positive; HER2+; Advanced Metastatic Breast Cancer; TYVERB; TYKERB
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Protein Kinase Inhibitors; Capecitabine; Lapatinib
• Other Study ID Numbers: EGF109491; CLAP016A2304 (OTHER: Novartis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No