Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12610000347066
Ethics application status
Approved
Date submitted
21/04/2010
Date registered
29/04/2010
Date last updated
8/04/2021
Date data sharing statement initially provided
8/04/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Lapatinib and vinorelbine in women with previously treated breast cancer
Scientific title
Phase II, open-label trial of lapatinib and vinorelbine in women with previously treated human epidermal growth factor receptor 2 (HER2/neu) positive metastatic breast cancer to assess progression-free survival.
Secondary ID [1] 251653 0
nil
Universal Trial Number (UTN)
Trial acronym
TyN
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Breast Cancer 257221 0
breast cancer 295247 0
Condition category
Condition code
Cancer 257360 257360 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Subjects will receive lapatinib (Investigational product) 1250mg daily, orally continuously with vinorelbine (Non-Investigational product) 20mg/m2 intravenously over 6 minutes (IV) Day 1 and Day 8 every 3 weeks until disease progression
Intervention code [1] 256342 0
Treatment: Drugs
Comparator / control treatment
None
Control group
Uncontrolled

Outcomes
Primary outcome [1] 258270 0
To evaluate the progression-free survival (PFS) in subjects with Her2/neu positive metastatic breast cancer treated with lapatinib and vinorelbine following trastuzumab-based therapy and lapatinib and capecitabine by clinical examination, computerised tomography (CT) scan and bone scan
Timepoint [1] 258270 0
The primary efficacy outcome is progression-free survival defined as the time from the initiation of therapy (day 1 cycle 1) to objective disease progression every 6 weeks until 24 weeks and then 12 weekly thereafter (using investigator assessments of disease progression) or death from breast cancer or death due to any other cause.
Secondary outcome [1] 263932 0
Progression-free survival at specific intervals by clinical examination, CT scan and bone scan.
Timepoint [1] 263932 0
12,24 and 52 weeks after intervention commencement
Secondary outcome [2] 263933 0
Overall objective response rate (defined as Complete and Partial Response) as defined by (Response evaluation criteria in solid tumours) RECIST v1.1 in subjects with measurable disease.
Timepoint [2] 263933 0
Time to response is defined as the time from Day 1 cycle 1 to the first date (of two successive scans) where complete response (CR) or partial response (PR) is documented every 6 weeks until 24 weeks and then 12 weekly thereafter until disease progression or death.
Secondary outcome [3] 263934 0
Clinical Benefit Rate (defined by Complete Response + Partial Response + Stable Disease) will be assessed by clinical examination, CT and bone scan.
Timepoint [3] 263934 0
the duration of response will be determined as the time from the date of the first scan to demonstrate response until unequivocal progressive disease or death from any cause.
Secondary outcome [4] 263935 0
Pain evaluation and analgesia use over treatment period will be assessed using the Brief Pain Inventory instrument
Timepoint [4] 263935 0
The Brief Pain Inventory (BPI) will be used to quantify pain control during the course of the treatment at 6 weekly intervals.
Secondary outcome [5] 263936 0
Time to objective response is defined as the time from Day 1 cycle 1 to the first date (of two successive scans) where CR or PR is documented
Timepoint [5] 263936 0
Time to response is defined as the time from Day 1 cycle 1 to the first date (of two successive scans) where CR or PR is documented
Secondary outcome [6] 263938 0
Overall survival by 12 weekly contact followup
Timepoint [6] 263938 0
Overall survival is defined as the time from the date of Day 1 cycle 1 to the documented date of death up until 2 years following completion of treatment
Secondary outcome [7] 263939 0
Adverse events of special interest e.g. liver chemistry abnormalities, cardiac dysfunction, diarrhea, constipation, abdominal pain, skin rash and neuropathy by blood tests, cardiac scans and clinical examination.
Timepoint [7] 263939 0
Duration of Study period. It is estimated that the study will be completed by approximately March 2012

Eligibility
Key inclusion criteria
Electrocardiogram (ECG) with QTc interval less than or equal to 480 msecs .
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Subjects meeting any of the following History of allergic or hypersensitivity reactions to either study drug (or related compounds) or their excipients.
Females who are pregnant or continuing to breast-feed.
Subjects who have received more than 2 different types of treatment with a Her2/neu targeted therapy for metastatic breast cancer
Evidence of a significant medical illness, abnormal laboratory finding or adverse event from prior anti-cancer therapy that would, in the investigators judgment, make the subject inappropriate for this study .
Any serious psychiatric disorder, dementia or altered mental status that would interfere with the subject’s safety or compliance to the study procedures.
GI tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory gastrointestinal (GI) disease (e.g., Crohn’s, ulcerative colitis).
Current active hepatic or biliary disease (with exception of subjects with Gilbert’s syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
Active cardiac disease
Concurrent therapy given to treat cancer including treatment with hormonal therapy, an investigational agent or concurrent participation in another clinical trial involving anti-cancer investigational drug.
Administration of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study treatment.
Neuropathy = grade 2 at baseline
Subjects previously treated with any vinorelbine or capecitabine (other than with lapatinib)
Subjects cannot have received any other chemotherapy agent concurrent with trastuzumab and the taxane apart from the inclusion of a platinum agent in the first HER2/neu targeted regimen used in the metastatic setting .
Prior treatment with anthracyclines with a cumulative dose of doxorubicin > 400 mg/m2 or epirubicin >800mg /m2 or equivalent dose for other anthracyclines derivatives .
Subjects who have concurrent active infections requiring IV antibiotics or non-healing wound.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
30/05/2010
Actual
21/07/2010
Date of last participant enrolment
Anticipated
Actual
18/01/2012
Date of last data collection
Anticipated
Actual
3/10/2012
Sample size
Target
20
Accrual to date
Final
19
Recruitment in Australia
Recruitment state(s)
NSW,VIC,QLD,SA,WA

Funding & Sponsors
Funding source category [1] 256849 0
Commercial sector/Industry
Name [1] 256849 0
Investigator Initiated Research Grant from GlaxoSmithKline
Country [1] 256849 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Breast Cancer Research Centre of WA
Address
Mount Medical Centre, 146 Mounts Bay Rd, Perth Western Australia 6000
Country
Australia
Secondary sponsor category [1] 256121 0
None
Name [1] 256121 0
Address [1] 256121 0
Country [1] 256121 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 258864 0
Mount Hospital Ethics Committee
Ethics committee address [1] 258864 0
150 Mounts Bay Road, Perth WA 6000
Ethics committee country [1] 258864 0
Australia
Date submitted for ethics approval [1] 258864 0
19/03/2010
Approval date [1] 258864 0
16/06/2010
Ethics approval number [1] 258864 0
EC57.2

Summary
Brief summary
This study looks at the effectiveness of the drugs lapatinib and vinorelbine in treating breast cancer (HER2/neu positive type) which has spread to distant sites and has been previously treated.

Who is it for?
You can join this study if you are a woman with Her2-positive breast cancer which has spread to distant sites and has progressed after initial treatment with trastuzumab-based treatment followed by lapatinib-capecitabine.

Trial details
Participants will receive lapatinib (1250 mg orally once daily) continuously and vinorelbine (20 mg/m2 (intra venous) on Day 1 and Day 8, of a 21-day cycle. Treatment will continue until any major toxic symptoms occur, or the disease or symptoms progress. If the cancer fails to respond, the patient will stop the study treatment and enter into the Survival Follow Up, where the cancer will be managed at the investigator’s discretion. Regular tumour scans will be used to monitor the disease. Scans will be completed 6 weekly until week 24 and then every 12 weeks thereafter. Quality of Life questionnaire will be completed by the patient to evaluate their pain and pain-relief use during the treatment period. The best combination of drugs to use after HER2 positive breast cancer has progressed on lapatinib-capecitabine is not known. Vinorelbine and lapatinib both have activity for the treatment of breast cancer. The study aims to evaluate the effect of this combination of drugs on survival rates and quality of life.

Throughout the study the safety of the patient will be continually reviewed by the study doctor (physical examination, vital signs, side effects assessment & regular safety blood tests). Cardiac safety will be monitored by serial multi-gated acquisition scan (MUGA) or Echocardiograph at weeks 12, 24 & 52.

For the first 5 patients enrolled in the study the Data Safety Monitoring Committee will review all side effects experienced during the course of cycle 1 and 2. This is to ensure that this treatment combination does not cause unacceptable side effects in a group of patients who have already received several lines of anti-cancer treatment.

Overall survival will be assessed by contacting the patients every 3 months during the Survival follow up part of the study.
Trial website
Trial related presentations / publications
Phase II, open-label trial of lapatinib and vinorelbine in women with previously treated HER2-positive metastatic breast cancer AJCO Vol10, pages 368-375, Dec 2014
Public notes

Contacts
Principal investigator
Name 31077 0
Prof Arlene Chan
Address 31077 0
Breast Cancer Research Centre - WA
Hollywood Private Hospital
Entrance 3, Lower Ground Floor
101 Monash Avenue
Nedlands WA 6009
Country 31077 0
Australia
Phone 31077 0
+61 8 6500 5555
Fax 31077 0
Email 31077 0
[email protected]
Contact person for public queries
Name 14324 0
Jeannette Devoto
Address 14324 0
Breast Cancer Research Centre-WA
Hollywood Private Hospital
Entrance 3, Lower Ground Floor
101 Monash Avenue
Nedlands WA 6009
Country 14324 0
Australia
Phone 14324 0
+ 61 8 6500 5556
Fax 14324 0
+ 61 8 6500 5599
Email 14324 0
[email protected]
Contact person for scientific queries
Name 5252 0
Jeannette Devoto
Address 5252 0
Breast Cancer Research Centre-WA
Hollywood Private Hospital
Entrance 3, Lower Ground Floor
101 Monash Avenue
Nedlands WA 6009
Country 5252 0
Australia
Phone 5252 0
+61 8 6500 5556
Fax 5252 0
+ 61 8 6500 5599
Email 5252 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Unavailable


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.