Lapatinib in Combination With Vinorelbine

Cancer Clinical Trial

— VITAL  

Official title:

A Phase II, Randomised, Multi-Centre Study Evaluating Lapatinib in Combination With Vinorelbine or Capecitabine in Women With ErbB2 Overexpressing Metastatic Breast Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01013740
• Other study ID #: 112620
• Status: Active, not recruiting
• Phase: Phase 2
• First received: October 29, 2009
• Last updated: November 5, 2015
• Start date: November 2009
• Est. completion date: June 2016

Study information

• Verified date: November 2015
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Agencia Española del Medicamento y Productos SanitariosItaly: Isituto Superiore di Sanita'Poland: Centralna Ewidencja Badan Klinicznych Urzad Rejestracji Produktów Leczniczych, Wyrobów Medycznych i Produktów BiobójczychGermany: Bundesinstitut für Arzneimittel und MedizinprodukteFrance: Agence Française de Sécurité Sanitaire des Produits de SantéGreece: National Drug Organisation
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 112
• Est. completion date: June 2016
• Est. primary completion date: August 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cancer

Intervention

Drug:
• Vinorelbine
Vinorelbine
• Lapatinib
Lapatinib
• Capecitabine
Capecitabine

Locations

Country	Name	City	State
Bulgaria	GSK Investigational Site	Plovdiv
Bulgaria	GSK Investigational Site	Sofia
Bulgaria	GSK Investigational Site	Sofia
Bulgaria	GSK Investigational Site	Varna
Chile	GSK Investigational Site	Santiago	Región Metro De Santiago
Chile	GSK Investigational Site	Santiago	Región Metro De Santiago
Chile	GSK Investigational Site	Viña del Mar	Valparaíso
France	GSK Investigational Site	Bayonne
France	GSK Investigational Site	Marseille
France	GSK Investigational Site	Nîmes cedex 9
France	GSK Investigational Site	Saint-Cloud
Germany	GSK Investigational Site	Bad Nauheim	Hessen
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Chemnitz	Sachsen
Germany	GSK Investigational Site	Duesseldorf	Nordrhein-Westfalen
Germany	GSK Investigational Site	Frankfurt am Main	Hessen
Germany	GSK Investigational Site	Mainz	Rheinland-Pfalz
Germany	GSK Investigational Site	Moenchengladbach	Nordrhein-Westfalen
Germany	GSK Investigational Site	Muenchen	Bayern
Germany	GSK Investigational Site	München	Bayern
Germany	GSK Investigational Site	Rheinfelden	Baden-Wuerttemberg
Germany	GSK Investigational Site	Velbert	Nordrhein-Westfalen
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Heraklion,Crete
Greece	GSK Investigational Site	Thessaloniki
Italy	GSK Investigational Site	Ancona	Marche
Italy	GSK Investigational Site	Brescia	Lombardia
Italy	GSK Investigational Site	Brindisi	Puglia
Italy	GSK Investigational Site	Catania	Sicilia
Italy	GSK Investigational Site	Catania	Sicilia
Italy	GSK Investigational Site	Genova	Liguria
Italy	GSK Investigational Site	Torino	Piemonte
Italy	GSK Investigational Site	Verona	Veneto
Mexico	GSK Investigational Site	Monterrey	Nuevo León
Mexico	GSK Investigational Site	Oaxaca
Poland	GSK Investigational Site	Gdansk
Poland	GSK Investigational Site	Gliwice
Poland	GSK Investigational Site	Konin
Poland	GSK Investigational Site	Lodz
Poland	GSK Investigational Site	Lublin
Poland	GSK Investigational Site	Olsztyn
Poland	GSK Investigational Site	Warszawa
Serbia	GSK Investigational Site	Belgrad
Serbia	GSK Investigational Site	Sremska Kamenica
Spain	GSK Investigational Site	Fuenlabrada (Madrid)
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Marbella
Spain	GSK Investigational Site	Pamplona
Spain	GSK Investigational Site	Reus
Spain	GSK Investigational Site	Segovia
Spain	GSK Investigational Site	Vigo (Pontevedra)
Spain	GSK Investigational Site	Zamora

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Secondary	Number of Participants With Overall Response (OR), as Assessed by the Investigator in the Randomized Phase	OR is defined as the number of participants achieving either a confirmed complete response (CR: the disappearance of all target lesions [TLs]) or partial response (PR: a >=30% decrease in the sum of the longest diameter [LD] of the TLs, taking as reference the baseline sum LD) as assessed by the investigator as the best OR.	From randomization until disease progression, death, or discontinuation from the study (average of 27 study weeks)	No
Secondary	Overall Survival (OS)	OS is defined as the time from randomization to the date of death due to any cause. Participants who had not died were censored at the date of the last adequate tumor assessment at the time of the cut-off.	From the date of randomization until death (average of 55 study weeks)	No
Secondary	Duration of Response (DOR) in the Randomized Phase	DOR is defined as the time from the first documented evidence of response (CR or PR) until the first documented sign of disease progression (a >=20% increase in the sum of the LD of TLs, taking as reference the smallest sum LD recorded since the treatment started or the appearance of >=1 new lesion) or death, if sooner. CR=the disappearance of all TLs. PR=a >=30% decrease in the sum of the LD of target lesions, taking as a reference the Baseline sum LD.	From the time of the first documented confirmed complete or partial response until disease progression or death, if sooner (average of 27 study weeks)	No
Secondary	Time to Response in the Randomized Phase	Time to response is defined as the time from randomization until the first documented evidence of CR (the disappearance of all TLs) or PR (a >=30% decrease in the sum of the LD of the TLs, taking as a reference the basline sum LD) (whichever status is recorded first). When tumor response was confirmed at a repeat assessment, the time to response was taken to be the first time that the response was observed.	From randomization until the time of the first documented confirmed CR or PR (average of 27 study weeks)	No
Secondary	Number of Participants With Clinical Benefit (CB) in the Randomized Phase	CB is defined as the the number of participants achieving either a confirmed CR or PR or having stable disease (SD) for at least 24 weeks (i.e., approximately 6 months). CR=the disappearance of all TLs. PR=a >=30% decrease in the sum of the LD of TLs, taking as a reference the Baseline sum LD. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD=at least a 20% increase in the sum of the LD of target lesions, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of >=1 new lesion). Participants with unknown or missing responses were treated as non-responders.	From randomization until disease progression, death, or discontinuation from the study (average of 27 study weeks)	No
Secondary	Area Under the Concentration-time Curve Over the Dosing Interval (AUC-tau) for Vinorelbine	AUC-tau is defined as the area under the concentration-time curve over a dosing interval at steady state, where tau is the length of the dosing interval. The AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. Pharmacokinetic (PK) parameters were to be assessed in an optional sub-study. No participants were enrolled in this optional sub-study; thus, no PK data are available.	Days 1 and 8; 0 to 24 hours post-dose	No
Secondary	Maximum Concentration (Cmax) for Vinorelbine	Cmax is defined as the maximum observed plasma or serum concentration after administration of the drug. PK parameters were to be assessed in an optional sub-study. No participants were enrolled in this optional sub-study; thus, no PK data are available.	Days 1 and 8; 0 to 24 hours post-dose	No
Secondary	Number of Participants With Grade 4 and Grade 5 Adverse Events (AE)	An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Grades: 0 = no AE or within normal limits; 1 = mild AE; 2 = moderate AE; 3 = severe and undesirable AE; 4 = life-threatening or disabling AE; 5 = death related to AE.	From randomization until disease progression, death, or discontinuation from the study (average of 55 study weeks)	No