Study In Women And Men With Metastatic Breast Cancer That Have Overexpression Of ErbB2

NCT00281658 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: EGF104535CLAP016A2302
• Study Type: interventional
• Target: 444
• Locations: 8 countries
• Sites: 54

Brief Summary

This was a randomized, double-blind, placebo-controlled, multicenter, Phase III study to evaluate and compare the efficacy and safety of Lapatinib + Paclitaxel versus Placebo + Paclitaxel in men and women with ErbB2 amplified metastatic (Stage IV) breast cancer who had not received prior therapy for metastatic disease.

Conditions

Neoplasms, Breast

Keywords

ErbB2 positive; human epidermal growth factor receptor 2 positive (Her2+); metastatic breast cancer; Fluorescence in situ hybridization (FISH) positive; Stage IV

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS) at 53 Months

  Overall Survival (OS) was defined as the interval of time (in months) between the date of randomization and the date of death due to any cause.

  From date of randomization until date of death from any cause, assessed up to 53 months (Primary OS analysis cut-off date = 18-Jun-2010)

Secondary Outcomes (12)

• Overall Survival (OS) at 190 Months

  From date of randomization until date of death from any cause, assessed up to 190 months (Final OS analysis cut-off date = 23-Nov-2021)

• Progression-free Survival (PFS) by Investigator Assessment

  From date of randomization until date of progression or date of death from any cause, whichever comes first, assessed up to 190 months (Final analysis cut-off date = 23-Nov-2021)

• Overall Response Rate (ORR) by Investigator Assessment

  From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 190 months (Final analysis cut-off date = 23-Nov-2021)

• Clinical Benefit Rate (CBR)

  From date of randomization until date of progression or date of death from any cause, whichever comes first, assessed up to 53 months (Primary analysis cut-off date = 18-Jun-2010)

• Duration of Response (DOR)

  From date of confirmed CR or PR until date of progression or date of death from any cause, whichever comes first, assessed up to 190 months (Final analysis cut-off date = 23-Nov-2021)

Study Arms (4)

Paclitaxel and Lapatinib (Blinded)

EXPERIMENTAL

Paclitaxel and Lapatinib (Blinded)

Drug: Lapatinib (GW572016) oral tablets; Drug: Paclitaxel infusion

Paclitaxel and Placebo (Blinded)

ACTIVE COMPARATOR

Paclitaxel and Placebo (Blinded)

Drug: Paclitaxel infusion; Drug: Placebo

Open Label - Monotherapy (Extension Phase)

OTHER

Open Label - Monotherapy (Lapatinib)

Drug: Lapatinib (GW572016) oral tablets

Open Label - Combination Therapy (Extension Phase)

OTHER

Open Label - Combination Therapy (Lapatinib and Paclitaxel)

Drug: Lapatinib (GW572016) oral tablets; Drug: Paclitaxel infusion

Interventions

Lapatinib (GW572016) oral tablets DRUG

1500 mg oral daily continuously

Open Label - Combination Therapy (Extension Phase); Open Label - Monotherapy (Extension Phase); Paclitaxel and Lapatinib (Blinded)

Paclitaxel infusion DRUG

Paclitaxel 80 mg/m2 every 3 weeks, 4th week rest for minimum 6 months

Open Label - Combination Therapy (Extension Phase); Paclitaxel and Lapatinib (Blinded); Paclitaxel and Placebo (Blinded)

Placebo DRUG

Paclitaxel Matching Placebo

Paclitaxel and Placebo (Blinded)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent;
• Male or female ≥18 years;
• Histologically confirmed invasive breast cancer with stage IV disease; If the disease is restricted to a solitary lesion, its neoplastic nature should be confirmed by cytology or histology.
• Documented amplification of ErbB2 by fluorescence in situ hybridization (FISH) in primary or metastatic tumor tissue by the central laboratory for randomization into the study;
• If a taxane was administered in the neoadjuvant or adjuvant setting, progression must have occurred \>12 months after completion of this treatment and the patient recovered from all associated toxicities;
• 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;
• Bisphosphonate therapy for bone metastases and is allowed; however, treatment must be initiated prior to the first dose of investigational treatment. Prophylactic use of bisphosphonates in subjects without bone disease is not permitted, except for the treatment of osteoporosis;
• For those patients whose disease is ER+ and/or PR+ the following criteria should be met:
• Patients with visceral disease that requires chemotherapy (eg., patients with liver or lung metastases) Rapidly progressing or life threatening disease, as determined by the investigator Patients 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;
• 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;
• Archived tumor tissue available for testing;

You may not qualify if:

• 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. (Refer to Section 5.3 Efficacy for list sites considered to be non-measurable disease.);
• Received prior chemotherapy, immunotherapy, biologic therapy, or anti-ErbB1/ErbB2 therapy for metastatic disease.
• Prior therapy with an ErbB1 and/or ErbB2 inhibitor, other than trastuzumab in the adjuvant setting. If trastuzumab was administered in the adjuvant setting, then \> 12 months must have elapsed since completion of trastuzumab therapy;
• 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;
• 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;
• 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;
• Known history or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis;
• Concurrent treatment with prohibited medications, including herbal remedies and Chinese traditional medicines;

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (54)

Novartis Investigative Site

Salvador, Estado de Bahia, 40.050-410, Brazil

Location

Novartis Investigative Site

Salvador, Estado de Bahia, 40285-001, Brazil

Location

Novartis Investigative Site

Belo Horizonte, Minas Gerais, 30150-281, Brazil

Location

Novartis Investigative Site

Natal, Rio Grande do Norte, 59075-740, Brazil

Location

Novartis Investigative Site

Porto Alegre, Rio Grande do Sul, 90610 000, Brazil

Location

Novartis Investigative Site

Jaú, São Paulo, 17210-120, Brazil

Location

Novartis Investigative Site

Santo André, São Paulo, 09060-650, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 01221-020, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 03102-002, Brazil

Location

Novartis Investigative Site

Guangzhou, Guangdong, 510060, China

Location

Novartis Investigative Site

Wuhan, Hubei, 430030, China

Location

Novartis Investigative Site

Nanjing, Jiangsu, 210002, China

Location

Novartis Investigative Site

Nanjing, Jiangsu, 210009, China

Location

Novartis Investigative Site

Dalian, Liaoning, 116027, China

Location

Novartis Investigative Site

Xi'an, Shaanxi, 710032, China

Location

Novartis Investigative Site

Xi'an, Shaanxi, 710061, China

Location

Novartis Investigative Site

Jinan, Shandong, 250012, China

Location

Novartis Investigative Site

Jinan, Shandong, 250031, China

Location

Novartis Investigative Site

Jinan, Shandong, 250117, China

Location

Novartis Investigative Site

Hangzhou, Zhejiang, 310022, China

Location

Novartis Investigative Site

Beijing, 100021, China

Location

Novartis Investigative Site

Beijing, 100036, China

Location

Novartis Investigative Site

Beijing, 100071, China

Location

Novartis Investigative Site

Beijing, 100853, China

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Novartis Investigative Site

Chengdu, 610041, China

Location

Novartis Investigative Site

Chongqing, 400037, China

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Novartis Investigative Site

Dalian, 116011, China

Location

Novartis Investigative Site

Fuzhou, 350001, China

Location

Novartis Investigative Site

Fuzhou, 350014, China

Location

Novartis Investigative Site

Shanghai, 200032, China

Location

Novartis Investigative Site

Shanghai, 200070, China

Location

Novartis Investigative Site

Shanghai, 200433, China

Location

Novartis Investigative Site

Shenyang, 110015, China

Location

Novartis Investigative Site

Tianjin, 300060, China

Location

Novartis Investigative Site

Kowloon, Hong Kong

Location

Novartis Investigative Site

Pokfulam, Hong Kong

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Novartis Investigative Site

Tuenmen, Hong Kong

Location

Novartis Investigative Site

Lahore, 53400, Pakistan

Location

Novartis Investigative Site

Lahore, 54600, Pakistan

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Novartis Investigative Site

Lahore, Pakistan

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Novartis Investigative Site

Lima, Lima 34, Peru

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Novartis Investigative Site

Kazan', 420029, Russia

Location

Novartis Investigative Site

Moscow, 117997, Russia

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Novartis Investigative Site

Moscow, 125101, Russia

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Novartis Investigative Site

Moscow, 143423, Russia

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Novartis Investigative Site

Rostov-on-Don, 344037, Russia

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Novartis Investigative Site

Samara, 443031, Russia

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Novartis Investigative Site

Voronezh, 394062, Russia

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Novartis Investigative Site

Bangkok, 10400, Thailand

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Novartis Investigative Site

Chiang Mai, 50200, Thailand

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Novartis Investigative Site

Cherkasy, 18009, Ukraine

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Novartis Investigative Site

Chernihiv, 14029, Ukraine

Location

Novartis Investigative Site

Dnipropetrovsk, 49055, Ukraine

Location

Novartis Investigative Site

Zaporizhzhia, 69040, Ukraine

Location

Related Publications (2)

• Xu B, Guan Z, Shen Z, Tong Z, Jiang Z, Yang J, DeSilvio M, Russo M, Leigh M, Ellis C. Association of phosphatase and tensin homolog low and phosphatidylinositol 3-kinase catalytic subunit alpha gene mutations on outcome in human epidermal growth factor receptor 2-positive metastatic breast cancer patients treated with first-line lapatinib plus paclitaxel or paclitaxel alone. Breast Cancer Res. 2014 Jul 24;16(4):405. doi: 10.1186/s13058-014-0405-y.

  PMID: 25056500 DERIVED

• Guan Z, Xu B, DeSilvio ML, Shen Z, Arpornwirat W, Tong Z, Lorvidhaya V, Jiang Z, Yang J, Makhson A, Leung WL, Russo MW, Newstat B, Wang L, Chen G, Oliva C, Gomez H. Randomized trial of lapatinib versus placebo added to paclitaxel in the treatment of human epidermal growth factor receptor 2-overexpressing metastatic breast cancer. J Clin Oncol. 2013 Jun 1;31(16):1947-53. doi: 10.1200/JCO.2011.40.5241. Epub 2013 Mar 18.

  PMID: 23509322 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Lapatinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

The data collected for China patients after 01JUL2019 were excluded from analysis due to local regulations in China.

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2006
• First Posted: January 25, 2006
• Study Start: January 2, 2006
• Primary Completion: June 18, 2010
• Study Completion: November 23, 2021
• Last Updated: February 10, 2023
• Results First Posted: June 1, 2011

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will share

Locations

TH (2); HK (3); UA (4); CN (25); BR (9); PA (3); PE (1); RU (7)