Cetuximab and Cisplatin in the Treatment of "Triple Negative" (Estrogen Receptor [ER] Negative, Progesterone Receptor [PgR] Negative, and Human Epidermal Growth Factor Receptor 2 [HER2] Negative) Metastatic Breast Cancer

Breast Neoplasm Clinical Trial

— BALI-1  

Official title:

Randomized Phase II Trial With Cetuximab and Cisplatin in the Treatment of ER-negative, PgR-negative, HER2-negative Metastatic Breast Carcinoma ("Basal Like")

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00463788
• Other study ID #: EMR 200027-051
• Status: Completed
• Phase: Phase 2
• First received: April 19, 2007
• Last updated: January 20, 2014
• Start date: June 2007
• Est. completion date: February 2011

Study information

• Verified date: January 2014
• Source: Merck KGaA
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods AdministrationAustralia: Human Research Ethics CommitteeAustria: EthikkommissionAustria: Federal Office for Safety in Health CareGermany: Ethics CommissionGermany: Paul-Ehrlich-InstitutIreland: Research Ethics CommitteeIreland: Irish Medicines BoardIsrael: Ethics CommissionItaly: National Monitoring Centre for Clinical Trials - Ministry of HealthItaly: Ethics CommitteeNew Zealand: MedsafeNew Zealand: Ministry of HealthPortugal: Ethics Committee for Clinical ResearchPortugal: National Pharmacy and Medicines InstituteSpain: Agencia Española de Medicamentos y Productos SanitariosSpain: Ethics CommitteeUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to determine whether overall response to cetuximab combined with cisplatin is better than overall response to cisplatin alone together with showing that the overall response for cetuximab and cisplatin was above a pre-specified threshold of 0.2 in the treatment of "triple negative" metastatic breast cancer.

The secondary objective of this study is to compare the differences between the two treatment groups using the following criteria : Progression-Free Survival (PFS) Time, Overall Survival (OS), Time to Response (TTR) and Safety.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 181
• Est. completion date: February 2011
• Est. primary completion date: July 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed diagnosis of metastatic breast cancer (Stage IV)

• Estrogen Receptor [ER] negative, PgR negative and HER2 less than 3+ expression by immunohistochemistry (IHC)

• No more than 1 prior chemotherapy received for treating this metastatic breast cancer

• No more than 1 prior anthracycline and/or taxane regimen (either adjuvant or metastatic setting)

• Other protocol-defined inclusion criteria may apply

Exclusion Criteria:

• Prior platinum agent

• Prior mitomycin

• Known history of brain metastases

• Other protocol-defined exclusion criteria may apply

Study Design

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

Related Conditions & MeSH terms

• Breast Neoplasm
• Breast Neoplasms

Intervention

Drug:
• cetuximab, cisplatin
Subjects will receive an initial dose of cetuximab 400 milligram per square meter (mg/m^2) followed by weekly doses of 250 mg/m^2. All doses will be given by intravenous (IV) infusion. Subjects will receive cisplatin (75 mg/m^2 IV on Day 1) every 3 weeks, with a maximum of 6 cycles. Administration of the Investigational Medicinal Product (IMP) will be stopped upon the first occurrence of disease progression, unacceptable toxicity or withdrawal of consent.
• cisplatin
Subjects will receive cisplatin (75 mg/m^2 IV on Day 1) every 3 weeks, with a maximum of 6 cycles. Subjects have the option of receiving cetuximab plus cisplatin at progression within the first 6 cycles, or cetuximab alone at progression after the 6 cycles. Administration of the IMP will be stopped upon the first occurrence of disease progression (except in cisplatin arm where switch to cetuximab plus cisplatin, or cetuximab alone is possible), unacceptable toxicity or withdrawal of consent.

Locations

Country	Name	City	State
Australia	Research Site	Campbelltown	New South Wales
Australia	Research Site	Liverpool	New South Wales
Australia	Research Site	Malvern	Victoria
Australia	Research Site	Perth	Western Australia
Australia	Research Site	Wollongong	New South Wales
Austria	Research Site	Bludesch-Gais
Austria	Research Site	Salzburg
Austria	Research Site	Wien
Belgium	Research Site	Brussels
Belgium	Research Site	Edegem
Belgium	Research Site	Gent
Belgium	Research Site	Liège
Belgium	Research Site	Namur
Belgium	Research Site	Wilrijk
Germany	Research Site	Frankfurt am Main
Germany	Research Site	Heidelberg
Germany	Research Site	Kiel
Germany	Research Site	Köln
Germany	Research Site	München
Germany	Research Site	Rostock
Ireland	Research Site	Dublin
Israel	Research Site	Beer Sheba
Israel	Research Site	Haifa
Israel	Research Site	Jerusalem
Israel	Research Site	Kefar Sava
Israel	Research Site	Petah Tikva
Israel	Research Site	Rehovot
Israel	Research Site	Tel Aviv
Israel	Research Site	Tel Hashomer
Italy	Research Site	Genova
Italy	Research Site	Modena
New Zealand	Research Site	Christchurch
New Zealand	Research Site	Wellington
Portugal	Research Site	Coimbra
Portugal	Research Site	Lisboa
Portugal	Research Site	Porto
Spain	Research Site	Barcelona
Spain	Research Site	Madrid
Spain	Research Site	Murcia
Spain	Research Site	Palma de Mallorca
Spain	Research Site	Valencia
Spain	Research Site	Zaragoza
United Kingdom	Research Site	Cardiff
United Kingdom	Research Site	Guildford
United Kingdom	Research Site	London
United Kingdom	Research Site	Manchester

Sponsors (1)

Lead Sponsor	Collaborator
Merck KGaA

Countries where clinical trial is conducted

Australia,  Austria,  Belgium,  Germany,  Ireland,  Israel,  Italy,  New Zealand,  Portugal,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Best Overall Response (BOR)	Percentage of participants with best overall (objective) response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST).	Evaluations were performed every 6 weeks until progression reported between day of first participant randomized, 20 June 2007, until cut-off date, 31 July 2009	No
Secondary	Progression-Free Survival (PFS) Time	The PFS was defined as the duration from randomization until radiological progression according to investigator (based on RECIST) or death due to any cause. Only deaths within 85 days of last tumor assessment were considered. Participants without event were censored on the date of last tumor assessment.	Time from randomization to disease progression, death or last tumour assessment, reported between day of first participant randomized, 20 June 2007, until cut-off date, 31 July 2009	No
Secondary	Overall Survival (OS) Time	The OS time was defined as the time from randomization to death. Participants without event were censored at the last date known to be alive or at the clinical cut-off date, whatever was earlier.	Time from randomization to death or last day known to be alive, reported between day of first participant randomized, 20 June 2007, until cut-off date, 05 April 2010	No
Secondary	Time to Response (TTR)	The TTR was determined for participants whose confirmed BOR (based on RECIST) was either a CR or a PR . It was defined as the time from the first dose study treatment until the date of the first assessment of confirmed CR or PR.	Time from the first dose of study treatment (cetuximab or cisplatin) to first assessment of CR or PR, reported between day of first participant randomized, 20 June 2007, until cut-off date, 31 July 2009	No
Secondary	Safety- Number of Participants Experiencing Any Adverse Event (AE)	Number of participants experiencing any AE. AEs: Any untoward medical occurrence in the form of signs, clinically significant abnormalities in laboratory findings, diseases, symptoms, or worsening of complications.	Time from first dose up to 30 days after last dose of study treatment, reported between day of first dose of study treatment, 20 June 2007, until cut-off date 05 April 2010	Yes