Clinical trial NCT00508274: Lapatinib +Capecitabine Treatment for Advanced Metastatic Breast Cancer in Women From China
Official title: An Open-Label Multicenter Study Administering Lapatinib and Capecitabine (Xeloda) in Women With Advanced or Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Neoplasms, Breast
Keywords: Advanced Metastatic Breast Cancer
HER2 positive
HER2+
breast cancer
lapatinib
TYVERB
TYKERB
Capecitabine
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2007-07-27
Enrollment: 52
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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;

Primary outcomes:
measure: Clinical Benefit Rate (CBR)
timeFrame: 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 outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: 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.
measure: Six Months Progression-Free Survival
timeFrame: 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.
measure: Time to Response (TTR)
timeFrame: 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
measure: Duration of Response (DOR)
timeFrame: 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.
measure: Number of Participants With Central Nervous System (CNS) as First Site of Relapse
timeFrame: 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
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Guangzhou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Wuhan
country: China
facility: Novartis Investigative Site
state: Hubei
city: Nanjing
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Hangzhou
country: China
facility: Novartis Investigative Site
state: Zhejiang
city: Hangzhou
country: China
facility: Novartis Investigative Site
state: Zhejiang
city: Beijing
country: China
facility: Novartis Investigative Site
city: Beijing
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Hong Kong
country: Hong Kong
facility: Novartis Investigative Site
city: Shatin
country: Hong Kong
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: 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.