Lapatinib in Combination With Vinorelbine

NCT01013740 | Completed Phase 2 Results

• 1 other identifier: CLAP016A2205 / 112620
• Study Type: interventional
• Target: 112
• Locations: 10 countries
• Sites: 53

Brief Summary

This is a randomized, parallel-arm, open-label, multi-centre, Phase II study to determine the efficacy and safety of lapatinib in combination with vinorelbine or capecitabine in women with ErbB2 overexpressing metastatic breast cancer (MBC) who have received no more than one chemotherapeutic regimen in the metastatic setting.

Conditions

Cancer

Keywords

Neoplasms, Breast

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS) in the Randomized Phase

  PFS is defined as the time from randomization until the earliest date of disease progression (PD) or death due to any cause, if sooner. PD is defined as at least a 20 % increase in the sum of the longest diameter (LD) of target lesions, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of \>=1 new lesion.

  From randomization until disease progression, death, or discontinuation from the study (average of 27 study weeks)

Secondary Outcomes (8)

• Number of Participants With Overall Response (OR), as Assessed by the Investigator in the Randomized Phase

  From randomization until disease progression, death, or discontinuation from the study (average of 27 study weeks)

• Overall Survival (OS)

  From the date of randomization until death (average of 55 study weeks)

• Duration of Response (DOR) in the Randomized Phase

  From the time of the first documented confirmed complete or partial response until disease progression or death, if sooner (average of 27 study weeks)

• Time to Response in the Randomized Phase

  From randomization until the time of the first documented confirmed CR or PR (average of 27 study weeks)

• Number of Participants With Clinical Benefit (CB) in the Randomized Phase

  From randomization until disease progression, death, or discontinuation from the study (average of 27 study weeks)

Study Arms (2)

Lapatinib + Vinorelbine

EXPERIMENTAL

Lapatinib + Vinorelbine

Drug: Vinorelbine; Drug: Lapatinib

Lapatinib + Capecitabine

ACTIVE COMPARATOR

Lapatinib + Capecitabine

Drug: Lapatinib; Drug: Capecitabine

Interventions

Vinorelbine DRUG

Vinorelbine

Lapatinib + Vinorelbine

Lapatinib DRUG

Lapatinib

Lapatinib + Capecitabine; Lapatinib + Vinorelbine

Capecitabine DRUG

Capecitabine

Lapatinib + Capecitabine

Eligibility Criteria

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

You may qualify if:

• Signed informed consent prior to registration.
• Considered by the investigator to have a life expectancy of ≥12 weeks.
• Subjects must be female and have histologically - confirmed invasive breast cancer with Stage IV disease at primary diagnosis or at relapse after curative - intent surgery.
• Documented overexpression of ErbB2
• Subjects should have progressive disease following prior therapy which may include anthracyclines, taxanes, and trastuzumab.
• Females aged ≥18 years
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1.
• Subjects must have adequate organ and marrow function
• Subjects must have a cardiac ejection fraction of at least 50% and within the institutional range of normal.
• Radiotherapy prior to initiation of study medication is allowed to a limited area ( e . g . , palliative therapy ) , if it is not the sole site of disease.
• Subjects with stable central nervous system (CNS) metastases are permitted.
• Subject must be free of gastrointestinal diseases or any other conditions that impede swallowing, retaining, and absorption of oral medications.
• 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.

You may not qualify if:

• Subjects taking prohibited medications are not eligible for the study.
• Therapy with lapatinib, vinorelbine, or capecitabine prior to randomization into this study.
• Prior therapy with more than one chemotherapeutic regimen for metastatic breast cancer.
• Concurrent anticancer or concomitant radiotherapy treatment.
• History of uncontrolled or symptomatic angina; history of arrhythmias requiring medications ; clinically significant myocardial infarction \< 6 months from study entry; uncontrolled or symptomatic congestive heart failure; ejection fraction below the institutional normal limit; or any other cardiac condition, which in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient.
• Have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment).
• Use of an investigational drug within 30 days or 5 half - lives, whichever is longer, preceding the first dose of investigational treatment, or, concurrent treatment with an investigational agent or participation in another clinical trial involving investigational agents.
• Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to any of the agents used in this study or their excipients that in the opinion of the investigator or GSK Medical Monitor contraindicates their participation.
• Known deficiency for the enzyme dihydropyrimidine dehydrogenase (DPD).
• Known history of uncontrolled inter - current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia, or psychiatric illness / social situations that would limit compliance with study requirements.
• 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.
• Pregnant or lactating females at any time during the study (due to the potential teratogenic or abortifacient effects of lapatinib and breastfeeding).
• Subjects with diseases affecting gastrointestinal function resulting in an inability to take oral medication , including ; malabsorption syndrome, disease significantly affecting gastrointestinal function , or resection of the stomach , small bowel , or colon. Subjects with inflammatory bowel disease or ulcerative colitis are also excluded.
• Peripheral neuropathy of Grade 2 or greater.
• Unresolved or unstable, serious toxicity from prior administration of another investigational drug and / or of prior cancer treatment.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (53)

Novartis Investigative Site

Plovdiv, 4000, Bulgaria

Location

Novartis Investigative Site

Sofia, 1527, Bulgaria

Location

Novartis Investigative Site

Sofia, 1756, Bulgaria

Location

Novartis Investigative Site

Varna, 9010, Bulgaria

Location

Novartis Investigative Site

Santiago, Región Metro de Santiago, 750 1088, Chile

Location

Novartis Investigative Site

Santiago, Región Metro de Santiago, 7650635, Chile

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Novartis Investigative Site

Viña Del Mar, ValparaÃ-so, 2520612, Chile

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Novartis Investigative Site

Bayonne, 64100, France

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Novartis Investigative Site

Marseille, 13009, France

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Novartis Investigative Site

Nîmes Cedex 9, 30029, France

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Novartis Investigative Site

Saint-Cloud, 92210, France

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Novartis Investigative Site

Rheinfelden, Baden-Wurttemberg, 79618, Germany

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Novartis Investigative Site

München, Bavaria, 80638, Germany

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Novartis Investigative Site

Munich, Bavaria, 80337, Germany

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Novartis Investigative Site

Bad Nauheim, Hesse, 61231, Germany

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Novartis Investigative Site

Frankfurt am Main, Hesse, 60590, Germany

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Novartis Investigative Site

Düsseldorf, North Rhine-Westphalia, 40225, Germany

Location

Novartis Investigative Site

Mönchengladbach, North Rhine-Westphalia, 41061, Germany

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Novartis Investigative Site

Velbert, North Rhine-Westphalia, 42551, Germany

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Novartis Investigative Site

Mainz, Rhineland-Palatinate, 55131, Germany

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Novartis Investigative Site

Chemnitz, Saxony, 09116, Germany

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Novartis Investigative Site

Berlin, State of Berlin, 12200, Germany

Location

Novartis Investigative Site

Athens, 115 22, Greece

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Novartis Investigative Site

Athens, 115 28, Greece

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Novartis Investigative Site

Heraklion,Crete, 71110, Greece

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Novartis Investigative Site

Thessaloniki, 564 29, Greece

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Novartis Investigative Site

Brindisi, Apulia, 72100, Italy

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Novartis Investigative Site

Genoa, Liguria, 16132, Italy

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Novartis Investigative Site

Brescia, Lombardy, 25124, Italy

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Novartis Investigative Site

Turin, Piedmont, 10126, Italy

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Novartis Investigative Site

Catania, Sicily, 95124, Italy

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Novartis Investigative Site

Catania, Sicily, Italy

Location

Novartis Investigative Site

Ancona, The Marches, 60020, Italy

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Novartis Investigative Site

Verona, Veneto, 37135, Italy

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Novartis Investigative Site

Monterrey, Nuevo León, 64060, Mexico

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Novartis Investigative Site

Oaxaca City, Oaxaca, 68000, Mexico

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Novartis Investigative Site

Gdansk, 80-219, Poland

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Novartis Investigative Site

Gliwice, 44-101, Poland

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Novartis Investigative Site

Konin, 62-500, Poland

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Novartis Investigative Site

Lodz, 93-509, Poland

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Novartis Investigative Site

Lublin, 20-090, Poland

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Novartis Investigative Site

Olsztyn, 10-513, Poland

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Novartis Investigative Site

Warsaw, 04-125, Poland

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Novartis Investigative Site

Belgrade, Serbia

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Novartis Investigative Site

Kamenitz, 21204, Serbia

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Novartis Investigative Site

Fuenlabrada (Madrid), 28942, Spain

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Novartis Investigative Site

Madrid, 28046, Spain

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Novartis Investigative Site

Marbella, 29600, Spain

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Novartis Investigative Site

Pamplona, 31008, Spain

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Novartis Investigative Site

Reus, 43201, Spain

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Novartis Investigative Site

Segovia, 40002, Spain

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Novartis Investigative Site

Vigo (Pontevedra), 36204, Spain

Location

Novartis Investigative Site

Zamora, Spain

Location

Related Publications (2)

• Hoon SN, Lau PK, White AM, Bulsara MK, Banks PD, Redfern AD. Capecitabine for hormone receptor-positive versus hormone receptor-negative breast cancer. Cochrane Database Syst Rev. 2021 May 26;5(5):CD011220. doi: 10.1002/14651858.CD011220.pub2.

  PMID: 34037241 DERIVED

• Janni W, Sarosiek T, Karaszewska B, Pikiel J, Staroslawska E, Potemski P, Salat C, Brain E, Caglevic C, Briggs K, Mahood K, DeSilvio M, Marini L, Papadimitriou C. Final overall survival analysis of a phase II trial evaluating vinorelbine and lapatinib in women with ErbB2 overexpressing metastatic breast cancer. Breast. 2015 Dec;24(6):769-73. doi: 10.1016/j.breast.2015.08.005. Epub 2015 Sep 16.

  PMID: 26384789 DERIVED

MeSH Terms

Conditions

Neoplasms; Breast Neoplasms

Interventions

Vinorelbine; Lapatinib; Capecitabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Quinazolines; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Clinical Disclosure Office
• Organization: Novartis Pharmaceuticals

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 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: After disease progression in the Randomized Phase (in which participants received lapatinib plus vinorelbine), participants were given the option of crossing over to the alternative treatment arm (lapatinib plus capecitabine), and continuing in a post-progression Cross-over Phase.

Study Record Dates

• First Submitted: October 29, 2009
• First Posted: November 16, 2009
• Study Start: November 25, 2009
• Primary Completion: August 21, 2012
• Study Completion: March 1, 2016
• Last Updated: May 31, 2017
• Results First Posted: July 18, 2013

Record last verified: 2017-03

Locations

ES (8); IT (8); BU (4); FR (4); DE (11); GR (4); PL (7); ME (2); SE (2); CL (3)