Pazopanib Plus Lapatinib Compared To Lapatinib Alone In Subjects With Inflammatory Breast Cancer

NCT ID: NCT00558103

Last Updated: 2013-02-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 163 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-12-31
• Study Completion Date: 2011-12-31

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.

Conditions

Neoplasms, Breast

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

arm 1

Lapatinib

Group Type: ACTIVE_COMPARATOR

lapatinib

Intervention Type: DRUG

Oral administration

arm2

Pazopanib monotherapy (open label)

Group Type: ACTIVE_COMPARATOR

Pazopanib

Intervention Type: DRUG

Oral administration

arm3

Lapatinib+ pazopanib

Group Type: EXPERIMENTAL

lapatinib

Intervention Type: DRUG

Oral administration

Pazopanib

Intervention Type: DRUG

Oral administration

Interventions

lapatinib

Oral administration

Intervention Type: DRUG

Pazopanib

Oral administration

Intervention Type: DRUG

Other Intervention Names

Tykerb; Votrient

Eligibility 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 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.

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).

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

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Long Beach, California, United States

GSK Investigational Site

Sacramento, California, United States

GSK Investigational Site

Denver, Colorado, United States

GSK Investigational Site

Washington D.C., District of Columbia, United States

GSK Investigational Site

Chicago, Illinois, United States

GSK Investigational Site

Zion, Illinois, United States

GSK Investigational Site

Scarborough, Maine, United States

GSK Investigational Site

Detroit, Michigan, United States

GSK Investigational Site

Omaha, Nebraska, United States

GSK Investigational Site

Voorhees Township, New Jersey, United States

GSK Investigational Site

Durham, North Carolina, United States

GSK Investigational Site

Philadelphia, Pennsylvania, United States

GSK Investigational Site

Charleston, South Carolina, United States

GSK Investigational Site

Memphis, Tennessee, United States

GSK Investigational Site

Houston, Texas, United States

GSK Investigational Site

Ogden, Utah, United States

GSK Investigational Site

Seattle, Washington, United States

GSK Investigational Site

Perth, Western Australia, Australia

GSK Investigational Site

Brussels, , Belgium

GSK Investigational Site

Edegem, , Belgium

GSK Investigational Site

Jette, , Belgium

GSK Investigational Site

Wilrijk, , Belgium

GSK Investigational Site

Montreal, Quebec, Canada

GSK Investigational Site

Montreal, Quebec, Canada

GSK Investigational Site

Temuco, Región de La Araucania, Chile

GSK Investigational Site

Viña del Mar, Región de Valparaíso, Chile

GSK Investigational Site

Santiago, Región Metro de Santiago, Chile

GSK Investigational Site

Beijing, , China

GSK Investigational Site

Beijing, , China

GSK Investigational Site

Shanghai, , China

GSK Investigational Site

Tianjin, , China

GSK Investigational Site

Brno, , Czechia

GSK Investigational Site

Hradec Králové, , Czechia

GSK Investigational Site

Prague, , Czechia

GSK Investigational Site

Cairo, , Egypt

GSK Investigational Site

Bayonne, , France

GSK Investigational Site

Bordeaux, , France

GSK Investigational Site

Clermont-Ferrand, , France

GSK Investigational Site

Lille, , France

GSK Investigational Site

Lyon, , France

GSK Investigational Site

Marseille Cedex BP 156, , France

GSK Investigational Site

Mulhouse, , France

GSK Investigational Site

Paris, , France

GSK Investigational Site

Paris, , France

GSK Investigational Site

Saint-Cloud, , France

GSK Investigational Site

Saint-Herblain, , France

GSK Investigational Site

Tours, , France

GSK Investigational Site

Valenciennes, , France

GSK Investigational Site

Mannheim, Baden-Wurttemberg, Germany

GSK Investigational Site

Ulm, Baden-Wurttemberg, Germany

GSK Investigational Site

Aschaffenburg, Bavaria, Germany

GSK Investigational Site

Munich, Bavaria, Germany

GSK Investigational Site

Rosenheim, Bavaria, Germany

GSK Investigational Site

Frankfurt am Main, Hesse, Germany

GSK Investigational Site

Duisburg, North Rhine-Westphalia, Germany

GSK Investigational Site

Essen, North Rhine-Westphalia, Germany

GSK Investigational Site

Herne, North Rhine-Westphalia, Germany

GSK Investigational Site

Troisdorf, North Rhine-Westphalia, Germany

GSK Investigational Site

Velbert, North Rhine-Westphalia, Germany

GSK Investigational Site

Witten, North Rhine-Westphalia, Germany

GSK Investigational Site

Mainz, Rhineland-Palatinate, Germany

GSK Investigational Site

Lohsa, Saxony, Germany

GSK Investigational Site

Zwickau, Saxony, Germany

GSK Investigational Site

Pinneberg, Schleswig-Holstein, Germany

GSK Investigational Site

Berlin, State of Berlin, Germany

GSK Investigational Site

Berlin, State of Berlin, Germany

GSK Investigational Site

Athens, , Greece

GSK Investigational Site

Hong Kong, , Hong Kong

GSK Investigational Site

Sheung Wan, , Hong Kong

GSK Investigational Site

Tuenmen, , Hong Kong

GSK Investigational Site

Petah Tikva, , Israel

GSK Investigational Site

Ramat Gan, , Israel

GSK Investigational Site

Rehovot, , Israel

GSK Investigational Site

Zrifin, , Israel

GSK Investigational Site

Milan, Lombardy, Italy

GSK Investigational Site

Sassari, Sardinia, Italy

GSK Investigational Site

Prato (PO), Tuscany, Italy

GSK Investigational Site

Casablanca, , Morocco

GSK Investigational Site

Hassan Rabat, , Morocco

GSK Investigational Site

Rabat, , Morocco

GSK Investigational Site

Lahore, , Pakistan

GSK Investigational Site

Lahore, , Pakistan

GSK Investigational Site

Multan, , Pakistan

GSK Investigational Site

Lima, Lima Province, Peru

GSK Investigational Site

Cebu, , Philippines

GSK Investigational Site

Manila, , Philippines

GSK Investigational Site

Quezon City, , Philippines

GSK Investigational Site

Sampaloc Manila, , Philippines

GSK Investigational Site

Bucharest, , Romania

GSK Investigational Site

Cluj-Napoca, , Romania

GSK Investigational Site

Iași, , Romania

GSK Investigational Site

Chelyabinsk, , Russia

GSK Investigational Site

Kazan', , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Ryazan, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Singapore, , Singapore

GSK Investigational Site

Incheon, , South Korea

GSK Investigational Site

Seodaemun-gu, Seoul, , South Korea

GSK Investigational Site

Songpa-gu, Seoul, , South Korea

GSK Investigational Site

Barcelona, , Spain

GSK Investigational Site

Barcelona, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Málaga, , Spain

GSK Investigational Site

Seville, , Spain

GSK Investigational Site

Valencia, , Spain

GSK Investigational Site

Valencia, , Spain

GSK Investigational Site

Changhua, , Taiwan

GSK Investigational Site

Taipei, , Taiwan

GSK Investigational Site

Tao-Yuan County, , Taiwan

GSK Investigational Site

Bangkok, , Thailand

GSK Investigational Site

Khon Kaen, , Thailand

GSK Investigational Site

Lampang, , Thailand

GSK Investigational Site

Phitsanulok, , Thailand

GSK Investigational Site

Ariana, Tunis, , Tunisia

GSK Investigational Site

Sfax, , Tunisia

GSK Investigational Site

Sousse, , Tunisia

GSK Investigational Site

Istanbul, , Turkey (Türkiye)

GSK Investigational Site

Izmir, , Turkey (Türkiye)

GSK Investigational Site

Northwood, Middlesex, United Kingdom

GSK Investigational Site

Bebington, Wirral, , United Kingdom

GSK Investigational Site

London, , United Kingdom

GSK Investigational Site

Sutton, , United Kingdom

Countries

United States; Australia; Belgium; Canada; Chile; China; Czechia; Egypt; France; Germany; Greece; Hong Kong; Israel; Italy; Morocco; Pakistan; Peru; Philippines; Romania; Russia; Singapore; South Korea; Spain; Taiwan; Thailand; Tunisia; Turkey (Türkiye); United Kingdom

Other Identifiers

VEG108838

Identifier Type: -

Identifier Source: org_study_id