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

NCT00558103 | Completed Phase 2 Results DMC

• 1 other identifier: VEG108838
• Study Type: interventional
• Target: 163
• Locations: 27 countries
• Sites: 124

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

Keywords

GW572016; Breast Cancer; RECIST; Inflammatory Breast Cancer; Pazopanib; ErbB2; Cutaneous Disease; Tykerb; Inflammatory; Skin; Her2; Lapatinib; GW786034

Outcome Measures

Primary Outcomes (1)

• 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

  RECIST-based response assessment was done at Weeks (Wks) 4 and 8 and every 8 weeks thereafter. Cutaneous disease assessment was done at Wk 4 and every 4 weeks thereafter. OR was evaluated when the skin and RECIST assessments coincided. Per RECIST, CR is the disappearance of all target and non-target lesions; PR is at least a 30 percent (%) decrease in the sum of the longest diameter (LD) of target lesions, taking as a reference the baseline sum LD. Cutaneous disease contained non-measurable and measurable skin disease, which was assessed by skin assessment tools.

  Baseline until disease progression/recurrence was documented, assessed for up to 66 weeks

Secondary Outcomes (3)

• Median Duration of Response,Defined as the First Documented Evidence of CR or PR Until the First Documentation of Disease Progression

  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

• 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)

  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

• Overall Survival

  From the date of randomization until the date of death due to any cause, assessed for up to 163 weeks

Study Arms (3)

arm 1

ACTIVE COMPARATOR

Lapatinib

Drug: lapatinib

arm2

ACTIVE COMPARATOR

Pazopanib monotherapy (open label)

Drug: Pazopanib

arm3

EXPERIMENTAL

Lapatinib+ pazopanib

Drug: lapatinib; Drug: Pazopanib

Interventions

lapatinib DRUG

Oral administration

Also known as: Tykerb

arm 1; arm3

Pazopanib DRUG

Oral administration

Also known as: Votrient

arm2; arm3

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (126)

GSK Investigational Site

Long Beach, California, 90806, United States

Location

GSK Investigational Site

Sacramento, California, 95816, United States

Location

GSK Investigational Site

Denver, Colorado, 80205, United States

Location

GSK Investigational Site

Washington D.C., District of Columbia, 20010, United States

Location

GSK Investigational Site

Chicago, Illinois, 60637, United States

Location

GSK Investigational Site

Zion, Illinois, 60099, United States

Location

GSK Investigational Site

Scarborough, Maine, 4074, United States

Location

GSK Investigational Site

Detroit, Michigan, 48201, United States

Location

GSK Investigational Site

Omaha, Nebraska, 68114, United States

Location

GSK Investigational Site

Voorhees Township, New Jersey, 08043, United States

Location

GSK Investigational Site

Durham, North Carolina, 27710, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19111, United States

Location

GSK Investigational Site

Charleston, South Carolina, 29425, United States

Location

GSK Investigational Site

Memphis, Tennessee, 38138, United States

Location

GSK Investigational Site

Houston, Texas, 77030, United States

Location

GSK Investigational Site

Ogden, Utah, 84403, United States

Location

GSK Investigational Site

Seattle, Washington, 98109, United States

Location

GSK Investigational Site

Perth, Western Australia, 6000, Australia

Location

GSK Investigational Site

Brussels, 1000, Belgium

Location

GSK Investigational Site

Edegem, 2650, Belgium

Location

GSK Investigational Site

Jette, 1090, Belgium

Location

GSK Investigational Site

Wilrijk, 2610, Belgium

Location

GSK Investigational Site

Montreal, Quebec, H2L 4M1, Canada

Location

GSK Investigational Site

Montreal, Quebec, H4J 1C5, Canada

Location

GSK Investigational Site

Temuco, Región de La Araucania, 481-0469, Chile

Location

GSK Investigational Site

Viña del Mar, Región de Valparaíso, 254-0364, Chile

Location

GSK Investigational Site

Santiago, Región Metro de Santiago, 7500921, Chile

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GSK Investigational Site

Beijing, 100021, China

Location

GSK Investigational Site

Beijing, 100071, China

Location

GSK Investigational Site

Shanghai, 200032, China

Location

GSK Investigational Site

Tianjin, 300060, China

Location

GSK Investigational Site

Brno, 656 53, Czechia

Location

GSK Investigational Site

Hradec Králové, 500 05, Czechia

Location

GSK Investigational Site

Prague, 180 00, Czechia

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GSK Investigational Site

Cairo, 11796, Egypt

Location

GSK Investigational Site

Bayonne, 64100, France

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GSK Investigational Site

Bordeaux, 33076, France

Location

GSK Investigational Site

Clermont-Ferrand, 63011, France

Location

GSK Investigational Site

Lille, 59020, France

Location

GSK Investigational Site

Lyon, 69008, France

Location

GSK Investigational Site

Marseille Cedex BP 156, 13273, France

Location

GSK Investigational Site

Mulhouse, 68070, France

Location

GSK Investigational Site

Paris, 75248, France

Location

GSK Investigational Site

Paris, 75970, France

Location

GSK Investigational Site

Saint-Cloud, 92210, France

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GSK Investigational Site

Saint-Herblain, 44805, France

Location

GSK Investigational Site

Tours, 37044, France

Location

GSK Investigational Site

Valenciennes, 59322, France

Location

GSK Investigational Site

Mannheim, Baden-Wurttemberg, 68161, Germany

Location

GSK Investigational Site

Ulm, Baden-Wurttemberg, 89075, Germany

Location

GSK Investigational Site

Aschaffenburg, Bavaria, 63739, Germany

Location

GSK Investigational Site

Munich, Bavaria, 80637, Germany

Location

GSK Investigational Site

Rosenheim, Bavaria, 83022, Germany

Location

GSK Investigational Site

Frankfurt am Main, Hesse, 60596, Germany

Location

GSK Investigational Site

Duisburg, North Rhine-Westphalia, 47166, Germany

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GSK Investigational Site

Essen, North Rhine-Westphalia, 45122, Germany

Location

GSK Investigational Site

Herne, North Rhine-Westphalia, 44623, Germany

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GSK Investigational Site

Troisdorf, North Rhine-Westphalia, 53840, Germany

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GSK Investigational Site

Velbert, North Rhine-Westphalia, 42551, Germany

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GSK Investigational Site

Witten, North Rhine-Westphalia, 58452, Germany

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GSK Investigational Site

Mainz, Rhineland-Palatinate, 55131, Germany

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GSK Investigational Site

Lohsa, Saxony, 02999, Germany

Location

GSK Investigational Site

Zwickau, Saxony, 08060, Germany

Location

GSK Investigational Site

Pinneberg, Schleswig-Holstein, 25421, Germany

Location

GSK Investigational Site

Berlin, State of Berlin, 10367, Germany

Location

GSK Investigational Site

Berlin, State of Berlin, 12163, Germany

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GSK Investigational Site

Athens, 185 47, Greece

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GSK Investigational Site

Hong Kong, Hong Kong

Location

GSK Investigational Site

Sheung Wan, Hong Kong

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GSK Investigational Site

Tuenmen, Hong Kong

Location

GSK Investigational Site

Petah Tikva, 49100, Israel

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GSK Investigational Site

Ramat Gan, 52621, Israel

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GSK Investigational Site

Rehovot, 76100, Israel

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GSK Investigational Site

Zrifin, 70300, Israel

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GSK Investigational Site

Milan, Lombardy, 20141, Italy

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GSK Investigational Site

Sassari, Sardinia, 07100, Italy

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GSK Investigational Site

Prato (PO), Tuscany, 59100, Italy

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GSK Investigational Site

Casablanca, Morocco

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GSK Investigational Site

Hassan Rabat, Morocco

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GSK Investigational Site

Rabat, Morocco

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GSK Investigational Site

Lahore, 53400, Pakistan

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GSK Investigational Site

Lahore, 54600, Pakistan

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GSK Investigational Site

Multan, 60000, Pakistan

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GSK Investigational Site

Lima, Lima Province, Lima 34, Peru

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GSK Investigational Site

Cebu, 6000, Philippines

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GSK Investigational Site

Manila, 1000, Philippines

Location

GSK Investigational Site

Quezon City, 1101, Philippines

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GSK Investigational Site

Sampaloc Manila, 1008, Philippines

Location

GSK Investigational Site

Bucharest, 022328, Romania

Location

GSK Investigational Site

Cluj-Napoca, 400015, Romania

Location

GSK Investigational Site

Iași, 700106, Romania

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GSK Investigational Site

Chelyabinsk, 454087, Russia

Location

GSK Investigational Site

Kazan', 420111, Russia

Location

GSK Investigational Site

Moscow, 115478, Russia

Location

GSK Investigational Site

Ryazan, 390011, Russia

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GSK Investigational Site

Saint Petersburg, 197022, Russia

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GSK Investigational Site

Saint Petersburg, 197758, Russia

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GSK Investigational Site

Singapore, 169610, Singapore

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GSK Investigational Site

Incheon, 400-711, South Korea

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GSK Investigational Site

Seodaemun-gu, Seoul, 120-752, South Korea

Location

GSK Investigational Site

Songpa-gu, Seoul, 138-736, South Korea

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GSK Investigational Site

Barcelona, 08035, Spain

Location

GSK Investigational Site

Barcelona, 08036, Spain

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GSK Investigational Site

Madrid, 28033, Spain

Location

GSK Investigational Site

Madrid, 28040, Spain

Location

GSK Investigational Site

Madrid, 28041, Spain

Location

GSK Investigational Site

Málaga, 29010, Spain

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GSK Investigational Site

Seville, 41013, Spain

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GSK Investigational Site

Valencia, 46009, Spain

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GSK Investigational Site

Valencia, 46010, Spain

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GSK Investigational Site

Changhua, 500, Taiwan

Location

GSK Investigational Site

Taipei, 112, Taiwan

Location

GSK Investigational Site

Tao-Yuan County, 333, Taiwan

Location

GSK Investigational Site

Bangkok, 10330, Thailand

Location

GSK Investigational Site

Khon Kaen, 40000, Thailand

Location

GSK Investigational Site

Lampang, 52000, Thailand

Location

GSK Investigational Site

Phitsanulok, 65000, Thailand

Location

GSK Investigational Site

Ariana, Tunis, 2080, Tunisia

Location

GSK Investigational Site

Sfax, 3000, Tunisia

Location

GSK Investigational Site

Sousse, 4000, Tunisia

Location

GSK Investigational Site

Istanbul, 34390, Turkey (Türkiye)

Location

GSK Investigational Site

Izmir, Turkey (Türkiye)

Location

GSK Investigational Site

Northwood, Middlesex, HA6 2RN, United Kingdom

Location

GSK Investigational Site

Bebington, Wirral, CH63 4JY, United Kingdom

Location

GSK Investigational Site

London, SW3 6JJ, United Kingdom

Location

GSK Investigational Site

Sutton, SM2 5PT, United Kingdom

Location

MeSH Terms

Conditions

Breast Neoplasms; Inflammatory Breast Neoplasms

Interventions

Lapatinib; pazopanib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2007
• First Posted: November 14, 2007
• Study Start: December 1, 2007
• Primary Completion: May 1, 2011
• Study Completion: December 1, 2011
• Last Updated: February 4, 2013
• Results First Posted: July 18, 2012

Record last verified: 2013-01

Locations

FR (13); PH (4); CN (4); EG (1); ES (9); AU (1); IT (3); US (17); BE (4); PE (1); CA (2); CZ (3); PA (3); RU (6); CL (3); RO (3); TU (3); KR (3); GR (1); DE (18); SG (1); IL (4); TH (4); GB (4); TW (3); MO (3); HK (3)