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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00558103




Registration number
NCT00558103
Ethics application status
Date submitted
9/11/2007
Date registered
14/11/2007
Date last updated
4/02/2013

Titles & IDs
Public title
Pazopanib Plus Lapatinib Compared To Lapatinib Alone In Subjects With Inflammatory Breast Cancer
Scientific title
A Randomized, Multicenter, Phase III Study Comparing the Combination of Pazopanib and Lapatinib Versus Lapatinib Monotherapy in Patients With ErbB2 Over-expressing Inflammatory Breast Cancer
Secondary ID [1] 0 0
VEG108838
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neoplasms, Breast 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - lapatinib
Treatment: Drugs - Pazopanib

Active Comparator: arm 1 - Lapatinib

Active Comparator: arm2 - Pazopanib monotherapy (open label)

Experimental: arm3 - Lapatinib+ pazopanib


Treatment: Drugs: lapatinib
Oral administration

Treatment: Drugs: Pazopanib
Oral administration
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Overall Response (OR), Defined as Those Participants Achieving Complete Response (CR) or Partial Response (PR), Assessed Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0 and Cutaneous Lesions
Timepoint [1] 0 0
Baseline until disease progression/recurrence was documented, assessed for up to 66 weeks
Secondary outcome [1] 0 0
Median Duration of Response,Defined as the First Documented Evidence of CR or PR Until the First Documentation of Disease Progression
Timepoint [1] 0 0
From the date of the first documented evidence of CR or PR until the date of the first documented disease progression or death, assessed for up to 62 weeks
Secondary outcome [2] 0 0
Progression-free Survival, Defined as the Interval Between the Date of Randomization and the Earliest Date of Disease Progression (PD) or Death Due to Any Cause (Defined by an Investigator Review of Lesions Based on RECIST and Cutaneous Disease)
Timepoint [2] 0 0
From the date of the randomization until the earliest date of disease progression or death due to any cause, assessed for up to 66 weeks
Secondary outcome [3] 0 0
Overall Survival
Timepoint [3] 0 0
From the date of randomization until the date of death due to any cause, assessed for up to 163 weeks

Eligibility
Key inclusion criteria
Inclusion criteria:

Specific information regarding warnings, precautions, contraindications, adverse events,
and other pertinent information on the investigational product that may impact patient
eligibility is provided in the pazopanib IB and lapatinib prescribing information (or the
lapatinib IB).

For Cohort 1 of this study, eligible patients met inclusion criteria outlined in the
original version of the protocol and protocol amendment 1.

For Cohort 2 of this study, eligible patients must meet all of the following criteria:

- Patients must have evaluable Inflammatory Breast Cancer (IBC) substantiated by all of
the following prior to randomization:

- History of invasive breast cancer documented by a biopsy and accompanying pathology
report

- Current photographs* (global view and close-up views of all skin lesions) submitted at
screening demonstrating unequivocal evidence of IBC as determined by either the
medical monitor alone or in consultation with one or more of the study Principal
Investigators.

- All patients must have photography at screening. Canfield Scientific Inc. will provide
centralized monitoring, tracking, and collection of patients' photographs throughout
the study. Screening photographs must be uploaded to the Canfield Scientific Inc
website and approved by Canfield Scientific Inc, as the central photography vendor.
The photographs, along with the completed Inflammatory Breast Cancer Skin Assessment
Tool (IBSAT), must be reviewed and approved by GSK before a patient can be randomized.
Sites should allow a minimum of 3 business days for this process. Sites submitting
quality photographs and IBSATs on a regular basis will receive an exemption from this
requirement for future patients.

- Patients with secondary IBC are eligible.

- Measurable lesions (cutaneous or radiographic) may be in the field of prior standard
or palliative radiation therapy; however, there must be at least a 4 week period
between the last radiation treatment and the baseline scan documenting disease status
for the lesion to be measurable. If the irradiated lesion is the only site of disease,
documented progression of the irradiated lesion is required.

- Disease progression or relapse following treatment for invasive breast cancer, which
must have included a chemotherapy regimen. In regions where trastuzumab is available
with no barriers to access*, patients must have received prior trastuzumab in addition
to chemotherapy in order to be eligible. * (Barriers to access may include financial
considerations.)

- Unequivocal ErbB2 overexpressing breast cancer, defined as 3+ staining by
immunohistochemistry (IHC), or 2+ staining by IHC in conjunction with ErbB2 gene
amplification by FISH/CISH, or ErbB2 gene amplification by FISH/CISH alone (in
subjects whose tumor blocks were not assessed by IHC). ErbB2 gene amplification is
defined by: > six (6) ErbB2 gene copies/nucleus for test systems without an internal
control probe or an ErbB2/CEP 17 ratio of more than 2.2.

Sites must submit a copy of the laboratory report demonstrating unequivocal ErbB2
overexpression, if testing performed at a local laboratory, with the screening worksheet.
Archived tumor must be provided for all patients for ErbB2 FISH testing by the central
laboratory. Patients will remain on study based on local ErbB2 expression results. If
archived tumor is not available, a biopsy must be obtained at screening and sent to TMD
Laboratories for ErbB2 FISH testing.

- Patients must provide written informed consent prior to performance of study-specific
procedures or assessments, and must be willing to comply with treatment and follow up.
Procedures conducted as part of the patient's routine clinical management (e.g., blood
count, imaging study) and obtained prior to signing of informed consent may be utilized for
screening or baseline purposes provided these procedures are conducted as specified in the
protocol.

Note: Informed consent may be obtained prior to the protocol-specified screening window
(i.e. Day -14 to Day -1).

- Females age = 18 years, except in Tunisia. In Tunisia, patients must be = 20 years to
be eligible for this study.

- Adequate organ function as defined below:

- System (Laboratory Values)

- Hematologic:Absolute neutrophil count (ANC)(= 1.5 X 10^9/L)Hemoglobin1(=9
g/dL)Platelets(=100 X 10^9/L)International normalized ratio (INR)(= 1.2 X upper limit
of normal (ULN))Partial thromboplastin time (PTT)(=1.2 X ULN)

- Hepatic:Total bilirubin2 (= 1.5 X upper limit of normal (ULN))AST and ALT(= 2.5 X ULN)

- Renal:Serum Creatinine (= 1.5 mg/dL)Or, if serum creatinine >1.5 mg/dL,

- Calculated creatinine clearance(=50 mL/min)

- Urine Protein to Creatinine Ratio(<1)

- Patients may not have had a transfusion within 7 days of screening assessment.

- Exception: Patients with elevated bilirubin levels due to Gilberts syndrome are
eligible.

- Cardiac ejection fraction within the institutional range of normal as measured by
echocardiogram. MUGA scans will be accepted in cases where an echocardiogram cannot be
performed or is inconclusive or where MUGA scans are the accepted standard. Patients
with known history of uncontrolled or symptomatic angina, arrhythmias, or congestive
heart failure are not eligible.

- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

- A female is eligible to enter and participate in this study if she is of:

Non-childbearing potential (i.e., physiologically incapable of becoming pregnant),
including any female who has had:

- A hysterectomy

- A bilateral oophorectomy (ovariectomy)

- A bilateral tubal ligation

- Is post-menopausal

- Patients not using hormone replacement therapy (HRT) must have experienced total
cessation of menses for = 1 year and be greater than 45 years in age, OR, in
questionable cases, have a follicle stimulating hormone (FSH) value >40 mIU/mL and an
estradiol value < 40pg/mL (<140 pmol/L).

Patients must discontinue HRT prior to study enrollment due to the potential for inhibition
of CYP enzymes that metabolize estrogens and progestins (See Section 8). For most forms of
HRT, at least 2-4 weeks must elapse between the cessation of HRT and determination of
menopausal status; length of this interval depends on the type and dosage of HRT. If a
female patient is determined not to be post-menopausal, they must use adequate
contraception, as defined immediately below.

Childbearing potential, including any female who has had a negative serum pregnancy test
within 2 weeks prior to the first dose of study treatment, preferably as close to the first
dose as possible, has used adequate contraception since the pregnancy test and agrees to
use adequate contraception as described below. GSK acceptable contraceptive methods, when
used consistently and in accordance with both the product label and the instructions of the
physician, are as follow:

- An intrauterine device with a documented failure rate of less than 1% per year.

- Vasectomized partner who is sterile prior to the female patient's entry and is the
sole sexual partner for that female.

- Complete abstinence from sexual intercourse for 14 days before exposure to
investigational product, through the dosing period, and for at least 21 days after the
last dose of investigational product.

- Double-barrier contraception (condom with spermicidal jelly, foam suppository, or
film; diaphragm with spermicide; or male condom and diaphragm with spermicide).

Note: Oral contraceptives are not reliable due to potential drug drug interactions.

Female patients who are lactating should discontinue nursing prior to the first dose of
investigational product and should refrain from nursing throughout the treatment period and
for 14 days following the last dose of investigational product.

- French patients: In France, a patient will be eligible for inclusion in this study only
if either affiliated to or a beneficiary of a social security category.
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
- Patients meeting any of the following criteria must not be enrolled in the study:

- Treatment in the 14 days prior to randomization with any cancer therapy (tumor
embolization, chemotherapy, immunotherapy, biological therapy, or hormonal therapy) or
treatment with mitomycin within 6 weeks prior to randomization. Such treatment may not
be resumed or begun after study entry. Note: Patients receiving LH-RH analogue therapy
prior to the study may continue to receive LH-RH analogues for the duration of study
participation. Bisphosphonates are permitted if started prior to Day 1.

- Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is
progressing in severity (with the exception of alopecia).

- Prior lapatinib therapy or other Her2/ErbB2 targeted therapy (except trastuzumab).

- Prior therapy with an anti-VEGF antibody or other VEGF/VEGF-R targeted therapy.

- Use of an investigational agent, including an investigational anti-cancer agent,
within 28 days or 5 half-lives, whichever is longer, prior to the first dose of
investigational product.

- Use of any prohibited medication within the timeframes listed in Section 8.1.3

- History of another malignancy.

- Note: Subjects who have had another malignancy and have been disease-free for 5 years,
or subjects with a history of completely resected non-melanomatous skin carcinoma or
successfully treated in situ carcinoma are eligible. If subject previously had breast
cancer, it must have been HER2+ with either 3+ overexpression by IHC or unequivocal
HER2 gene amplification by FISH or CISH.

- History or clinical evidence of central nervous system (CNS) metastases or
leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS
metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure
medication for 2 months prior to first dose of study drug. Screening with CNS imaging
studies (computed tomography [CT] or magnetic resonance imaging [MRI]) is required
only if clinically indicated or if the subject has a history of CNS metastases.

- Clinically significant gastrointestinal abnormalities that may increase the risk for
GI bleeding including, but not limited to:

- Active peptic ulcer disease

- Known intraluminal metastatic lesion/s with suspected bleeding

- Inflammatory bowel disease

- Ulcerative colitis, or other gastrointestinal conditions with increased risk of
perforation

- History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess
within 28 days prior to beginning study treatment.

- Clinically significant gastrointestinal abnormalities that may affect absorption of
investigational product including, but limited to:

- Malabsorption syndrome

- Major resection of the stomach or small bowel.

- Presence of uncontrolled infection.

- Prolongation of corrected QT interval (QTc) > 480 msecs.

- History of any one or more of the following cardiovascular conditions within the past
6 months:

- Cardiac angioplasty or stenting

- Myocardial infarction

- Unstable angina

- Arterial thrombosis

- Symptomatic peripheral vascular disease

- Class III or IV congestive heart failure, as defined by the New York Heart Association
(NYHA) (see Section 15.9 Appendix 9 for description).

- Poorly controlled hypertension [defined as systolic blood pressure (SBP) of =140mmHg
or diastolic blood pressure (DBP) of = 90mmHg].

Note: Initiation or adjustment of antihypertensive medication(s) is permitted during the
screening period, in order to control a patient's BP prior to randomization. Blood pressure
must be re-assessed on two occasions that are separated by a minimum of 1 hour. The mean
SBP / DBP values from each blood pressure assessment must be < 140/90mmHg in order for a
patient to be eligible for the study. See Section 6.2 and Section 6.4.2 for details on
blood pressure control and reassessment prior to study enrollment.

- History of cerebrovascular accident, including TIA, pulmonary embolism or deep venous
thrombosis (DVT).

- Prior major surgery or trauma within 28 days prior to first dose of investigational
product and/or presence of any non-healing wound, fracture, or ulcer (other than
ulcers due to inflammatory breast cancer).

- Evidence of active bleeding or bleeding diathesis.

- Hemoptysis within 6 weeks prior to first dose of investigational product.

- Known endobronchial lesions or involvement of large pulmonary vessels by tumor.

- Any serious and/or unstable pre-existing medical, psychiatric, or other condition that
could interfere with patient's safety, provision of informed consent, or compliance to
study procedures.

- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to pazopanib or lapatinib.

- 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).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/12/2007
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/12/2011
Sample size
Target
Accrual to date
Final
163
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
GSK Investigational Site - Perth
Recruitment postcode(s) [1] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
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California
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Colorado
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District of Columbia
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Illinois
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Maine
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Michigan
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Nebraska
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North Carolina
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South Carolina
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Tennessee
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Texas
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Utah
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Washington
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Belgium
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Bruxelles
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Belgium
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Edegem
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Belgium
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Jette
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Belgium
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Wilrijk
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Canada
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Quebec
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Chile
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Región De La Araucania
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Chile
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Región Metro De Santiago
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Chile
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Valparaíso
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Beijing
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China
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Brno
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Hradec Kralove
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Praha 8
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Egypt
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Cairo
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France
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Bayonne
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France
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Bordeaux
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France
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Clermont-Ferrand cedex
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France
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Lille
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France
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Lyon
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France
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Marseille Cedex BP 156
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France
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Mulhouse
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France
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Paris Cedex 20
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France
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Saint-Cloud
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Tours
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Bayern
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Hessen
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Germany
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Sachsen
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Petach Tikva
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Israel
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Ramat Gan
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Israel
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Rehovot
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Israel
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Zrifin
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Italy
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Italy
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Sardegna
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Italy
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Toscana
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Korea, Republic of
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Incheon City
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Korea, Republic of
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seodaemun-gu, Seoul
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Korea, Republic of
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songpa-gu, Seoul
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Morocco
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Casablanca
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Morocco
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Hassan Rabat
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Morocco
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Rabat
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Lahore
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Multan
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Lima
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Sampaloc Manila
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Romania
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Cluj-Napoca
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Iasi
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Singapore
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Sevilla
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Valencia
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Taiwan
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Changhua
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Taiwan
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Taipei
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Taiwan
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Tao-Yuan county
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Thailand
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Bangkok
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Thailand
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Khon Kaen
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Thailand
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Lampang
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Thailand
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Phitsanulok
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Tunisia
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Ariana, Tunis
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Tunisia
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Sfax
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Tunisia
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Sousse
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Turkey
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Istanbul
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Turkey
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Izmir
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United Kingdom
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Middlesex
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United Kingdom
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Bebington, Wirral
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United Kingdom
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London
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United Kingdom
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Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The double blind part of the study is being conducted to compare the efficacy and safety of
pazopanib in combination with lapatinib with that of lapatinib alone in subjects with
inflammatory breast cancer whose tumors overexpress the ErbB2 protein. There is also an
Open-label pazopanib arm to this study designed to test whether pazopanib given alone and
lapatinib given alone would be safe and effective to treat patients with inflammatory breast
cancer.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00558103
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00558103