Lapatinib in Combination With Vinorelbine

NCT ID: NCT01013740

Last Updated: 2017-05-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 112 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-11-25
• Study Completion Date: 2016-03-01

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.

Detailed Description

Approximately 105 subjects will be enrolled in the study and randomized 2:1 to one of the following regimens Arm A (n=70): Lapatinib 1250 mg orally once daily continuously plus Vinorelbine 20mg/m2 intravenously (IV) on day 1 and 8, every third week, or Arm B (n=35): Lapatinib 1250 mg orally once daily (QD) continuously plus Capecitabine 2000 mg/m2/day orally in 2 doses 12 hours apart on days 1-14 every third week. Randomization will be stratified according to the following variables: 1) Prior receipt of therapy for metastatic breast cancer (Yes or No), and 2) Site of metastatic disease (Visceral/Soft tissue or Bone-only). Subjects will receive randomized study treatment until disease progression or discontinuation of study treatment due to unacceptable toxicity, withdrawal of consent, lost to follow up, or death. All subjects who discontinue study treatment without documented progression will continue to be followed for progression according to protocol-schedule until new anti-cancer therapy is initiated and/or progression or death is documented. Survival data will be collected for all subjects to ensure a minimum of 18 months survival data. This study will include a safety run-in phase for approximately the first 30 subjects (20 randomized to lapatinib and vinorelbine; 10 to lapatinib and capecitabine).

Conditions

Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Lapatinib + Vinorelbine

Lapatinib + Vinorelbine

Group Type: EXPERIMENTAL

Vinorelbine

Intervention Type: DRUG

Vinorelbine

Lapatinib

Intervention Type: DRUG

Lapatinib

Lapatinib + Capecitabine

Lapatinib + Capecitabine

Group Type: ACTIVE_COMPARATOR

Lapatinib

Intervention Type: DRUG

Lapatinib

Capecitabine

Intervention Type: DRUG

Capecitabine

Interventions

Vinorelbine

Vinorelbine

Intervention Type: DRUG

Lapatinib

Lapatinib

Intervention Type: DRUG

Capecitabine

Capecitabine

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.
• Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Plovdiv, , Bulgaria

Novartis Investigative Site

Sofia, , Bulgaria

Novartis Investigative Site

Sofia, , Bulgaria

Novartis Investigative Site

Varna, , Bulgaria

Novartis Investigative Site

Santiago, Región Metro de Santiago, Chile

Novartis Investigative Site

Santiago, Región Metro de Santiago, Chile

Novartis Investigative Site

Viña Del Mar, ValparaÃ-so, Chile

Novartis Investigative Site

Bayonne, , France

Novartis Investigative Site

Marseille, , France

Novartis Investigative Site

Nîmes Cedex 9, , France

Novartis Investigative Site

Saint-Cloud, , France

Novartis Investigative Site

Rheinfelden, Baden-Wurttemberg, Germany

Novartis Investigative Site

München, Bavaria, Germany

Novartis Investigative Site

Munich, Bavaria, Germany

Novartis Investigative Site

Bad Nauheim, Hesse, Germany

Novartis Investigative Site

Frankfurt am Main, Hesse, Germany

Novartis Investigative Site

Düsseldorf, North Rhine-Westphalia, Germany

Novartis Investigative Site

Mönchengladbach, North Rhine-Westphalia, Germany

Novartis Investigative Site

Velbert, North Rhine-Westphalia, Germany

Novartis Investigative Site

Mainz, Rhineland-Palatinate, Germany

Novartis Investigative Site

Chemnitz, Saxony, Germany

Novartis Investigative Site

Berlin, State of Berlin, Germany

Novartis Investigative Site

Athens, , Greece

Novartis Investigative Site

Athens, , Greece

Novartis Investigative Site

Heraklion,Crete, , Greece

Novartis Investigative Site

Thessaloniki, , Greece

Novartis Investigative Site

Brindisi, Apulia, Italy

Novartis Investigative Site

Genoa, Liguria, Italy

Novartis Investigative Site

Brescia, Lombardy, Italy

Novartis Investigative Site

Turin, Piedmont, Italy

Novartis Investigative Site

Catania, Sicily, Italy

Novartis Investigative Site

Catania, Sicily, Italy

Novartis Investigative Site

Ancona, The Marches, Italy

Novartis Investigative Site

Verona, Veneto, Italy

Novartis Investigative Site

Monterrey, Nuevo León, Mexico

Novartis Investigative Site

Oaxaca City, Oaxaca, Mexico

Novartis Investigative Site

Gdansk, , Poland

Novartis Investigative Site

Gliwice, , Poland

Novartis Investigative Site

Konin, , Poland

Novartis Investigative Site

Lodz, , Poland

Novartis Investigative Site

Lublin, , Poland

Novartis Investigative Site

Olsztyn, , Poland

Novartis Investigative Site

Warsaw, , Poland

Novartis Investigative Site

Belgrade, , Serbia

Novartis Investigative Site

Kamenitz, , Serbia

Novartis Investigative Site

Fuenlabrada (Madrid), , Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Marbella, , Spain

Novartis Investigative Site

Pamplona, , Spain

Novartis Investigative Site

Reus, , Spain

Novartis Investigative Site

Segovia, , Spain

Novartis Investigative Site

Vigo (Pontevedra), , Spain

Novartis Investigative Site

Zamora, , Spain

Countries

Bulgaria; Chile; France; Germany; Greece; Italy; Mexico; Poland; Serbia; Spain

References

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.

Reference Type: DERIVED

PMID: 34037241 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26384789 (View on PubMed)

Other Identifiers

CLAP016A2205 / 112620

Identifier Type: -

Identifier Source: org_study_id