Pazopanib Plus Lapatinib Compared To Lapatinib Alone In Subjects With Advanced Or Metastatic Breast Cancer

NCT00347919 | Completed Phase 2 Results

• 1 other identifier: VEG20007
• Study Type: interventional
• Target: 189
• Locations: 16 countries
• Sites: 84

Brief Summary

This study is being conducted to compare the efficacy and safety of pazopanib in combination with lapatinib with that of lapatinib alone in subjects with locally advanced or metastatic breast cancer whose tumors overexpress the ErbB2 protein.

Conditions

Neoplasms, Breast

Keywords

GW786034; Quality of Life; GW572016; Lapatinib; Pazopanib; Metastatic; Breast cancer; Genetics; FISH; Advanced

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Progressive Disease at Week 12 in Cohort 1

  The percentage of participants with progressive disease (PD) 12 weeks after randomization was measured. Per Response Evaluation Criteria In Solid Tumors (RECIST), a response of PD is defined as a \>=20% increase in target lesions. Participants were also classified as having PD if their response at Week 12 was unknown or missing. Response was determined by an independent radiologist and by an investigator.

  Week 12

Secondary Outcomes (5)

• Overall Survival for Cohort 1

  Randomization until death due to any cause (up to 106.43 weeks)

• Response at Week 12 for Cohort 1 and Cohort 2

  Week 12

• Duration of Response in Cohort 1

  Time from first documented evidence of complete or partial response until the first documented sign of disease progression or death due to any cause (up to 106.71 weeks)

• Time to Response (Complete or Partial Response) in Cohort 1 and Cohort 2

  The time from randomization to the time of first documented evidence of complete or partial response (up to 81.14 weeks for Cohort 1 and 44.29 weeks for Cohort 2)

• Percentage of Participants With Progressive Disease at Week 12

  Week 12

Study Arms (3)

monotherapy arm

EXPERIMENTAL

1500 mg (6 x 250 mg tablets) oral lapatinib once daily

Drug: lapatinib (GW572016) 1500 mg

Cohort 1 combination arm

EXPERIMENTAL

1000 mg (4 x 250 mg tablets) of oral lapatinib and 400 mg (4 x 100 mg tablets) of oral pazopanib taken together once daily

Drug: pazopanib (GW786034) 400 mg; Drug: lapatinib (GW572016) 1000 mg

Cohort 2 combination arm

EXPERIMENTAL

1500 mg (6 x 250 mg tablets) of oral lapatinib and 800 mg (1 x 500 mg tablets plus 3 x 100 mg tablets) of oral pazopanib taken together once daily

Drug: lapatinib (GW572016) 1500 mg; Drug: pazopanib (GW786034) 800 mg

Interventions

pazopanib (GW786034) 400 mg DRUG

400 mg administered orally once daily

Cohort 1 combination arm

lapatinib (GW572016) 1500 mg DRUG

1500 mg administered orally once daily.

Cohort 2 combination arm; monotherapy arm

lapatinib (GW572016) 1000 mg DRUG

1000 mg administered orally once daily

Cohort 1 combination arm

pazopanib (GW786034) 800 mg DRUG

800 mg administered orally once daily

Cohort 2 combination arm

Eligibility Criteria

• Age: 21 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women ≥ 18 years of age with a life expectancy of ≥ 12 weeks.
• Note: National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and Alzheimer's Disease and Related Disorders Association (ADRDA).)
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.
• Histologically confirmed invasive breast cancer with incurable stage IIIb, stage IIIc with T4 lesion, or stage IV disease at primary diagnosis or at relapse after curative-intent surgery.
• No prior chemotherapy, immunotherapy, biologic therapy or anti-ErbB1/ErbB2 therapy for metastatic or recurrent disease (other than neoadjuvant or adjuvant therapy). Prior hormonal therapy (e.g., tamoxifen, raloxifen or an aromatase inhibitor) for advanced or metastatic disease is permitted provided at least 2 weeks have elapsed between the completion of the prior therapy and start of study drugs.
• Note: Subjects must have documented progressive disease (PD) or be intolerant to hormonal therapy. This must be documented in the source documentation.
• Prior neoadjuvant therapy and/or adjuvant therapy is permitted.
• Note:
• (a) Subjects who have received both neoadjuvant and adjuvant therapies must have at least 6 months between completion of the chemotherapy-component of adjuvant therapy and start of study drug(s)
• (b) Subjects who have received only adjuvant therapy must have at least 6 months between completion of the chemotherapy-component of adjuvant therapy and start of study drug(s)
• (c) Subjects who have received only neoadjuvant therapy must have at least 6 months between completion of neoadjuvant therapy and start of study drug(s)
• (d) Subjects who have received trastuzumab or hormonal agents as all or part of adjuvant therapy are eligible provided: (1) 2 weeks have elapsed since last dose (2) 6 months have elapsed between the start of trastuzumab or hormonal therapy and start of study drugs.
• Radiotherapy prior to initiation of randomized therapy to a limited area (e.g., palliative treatment for painful disease) other than the sole site of measurable and assessable disease is allowed however, subjects must have completed treatment at least 4 weeks prior to starting study drugs, and must have recovered from all treatment-related toxicities prior to starting pazopanib and/or lapatinib.
• Documented amplification of ErbB2 by Fluorescence In Situ Hybridization (FISH) in either the primary or metastatic tumor tissue. Archived tumor tissue must be provided for ErbB2 FISH testing by the central laboratory, which will be used to determine eligibility.
• Note: Subjects that have documented ErbB2 amplification based on prior FISH testing or documented ErbB2 overexpression based on prior immunohistochemistry (IHC) with a value of 3+ are eligible, however, archived tumor tissue must be provided for confirmation by the central laboratory. If the results from prior testing are not confirmed by the central laboratory, then the subject can continue to receive study drug(s) at the discretion of the investigator, but will be excluded from the statistical analysis.

You may not qualify if:

• Subjects with bilateral breast cancer or bone metastases as the only disease site.
• Patients with high disease burden defined as \>30% replacement of hepatic parenchyma with metastases, symptomatic pulmonary metastases (e.g., clinically significant dyspnea, cough, or chest pain attributable to pulmonary metastases), or \>3 visceral organs with tumor involvement.
• History of other malignancy. Subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.
• Sarcoma histology.
• Concurrent disease or condition that would make the subject inappropriate for study participation including (1) any unresolved or unstable, serious toxicity from prior administration of another investigational drug, (2) any serious medical disorder that would interfere with the subject's safety, obtaining informed consent or compliance to the study.
• 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 antiseizure medication for ³ 2 months prior to study enrollment. Routine 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.
• Malabsorption Syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel.
• Active peptic ulcer disease, inflammatory bowel disease, or other gastrointestinal condition increasing the risk of perforation; history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 4 weeks prior to beginning therapy.
• Presence of uncontrolled infection.
• Concurrent cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, hormonal therapy, and tumor embolization).
• Concurrent treatment with an investigational agent or participation in another clinical trial.
• Use of an investigational anti-cancer drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of pazopanib and/or lapatinib.
• Prior use of an investigational or licensed drug that targets either vascular endothelial growth factor (VEGF) or VEGF receptors, or ErbB2 (except for trastuzumab when used in the neo-adjuvant/adjuvant setting).
• Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib or lapatinib.
• Has taken/is taking prohibited medications, Lapatinib-related, orPazopanib-related.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (84)

GSK Investigational Site

Jonesboro, Arkansas, 72401, United States

Location

GSK Investigational Site

Alhambra, California, 91801, United States

Location

GSK Investigational Site

Bakersfield, California, 93309, United States

Location

GSK Investigational Site

Fullerton, California, 92835, United States

Location

GSK Investigational Site

Long Beach, California, 90813, United States

Location

GSK Investigational Site

Los Angeles, California, 90095-1752, United States

Location

GSK Investigational Site

Northridge, California, 91328, United States

Location

GSK Investigational Site

Oxnard, California, 93030, United States

Location

GSK Investigational Site

Redondo Beach, California, 90277, United States

Location

GSK Investigational Site

Santa Barbara, California, 93105, United States

Location

GSK Investigational Site

Santa Maria, California, 93454, United States

Location

GSK Investigational Site

Indianapolis, Indiana, 46202, United States

Location

GSK Investigational Site

Metairie, Louisiana, 70006, United States

Location

GSK Investigational Site

Henderson, Nevada, 89052, United States

Location

GSK Investigational Site

The Bronx, New York, 10461, United States

Location

GSK Investigational Site

Akron, Ohio, 44304, United States

Location

GSK Investigational Site

Dallas, Texas, 75390-9113, United States

Location

GSK Investigational Site

Lubbock, Texas, 79410, United States

Location

GSK Investigational Site

San Antonio, Texas, 78207, United States

Location

GSK Investigational Site

Edmonton, Alberta, T6G 1Z2, Canada

Location

GSK Investigational Site

Halifax, Nova Scotia, B3H 1V7, Canada

Location

GSK Investigational Site

Weston, Ontario, M9N 1N8, Canada

Location

GSK Investigational Site

Besançon, 25030, France

Location

GSK Investigational Site

Hyères, 83400, France

Location

GSK Investigational Site

Lille, 59020, France

Location

GSK Investigational Site

Lyon, 69437, France

Location

GSK Investigational Site

Marseille Cedex BP 156, 13273, France

Location

GSK Investigational Site

Paris, 75248, France

Location

GSK Investigational Site

Strasbourg, 67000, France

Location

GSK Investigational Site

Budapest, 1082, Hungary

Location

GSK Investigational Site

Budapest, 1122, Hungary

Location

GSK Investigational Site

Győr, H-9024, Hungary

Location

GSK Investigational Site

Bangalore, 560029, India

Location

GSK Investigational Site

Delhi, 110085, India

Location

GSK Investigational Site

Jaipur, 302004, India

Location

GSK Investigational Site

Mumbai, 400012, India

Location

GSK Investigational Site

Pune, 411 004, India

Location

GSK Investigational Site

Pune, 411001, India

Location

GSK Investigational Site

Trivandrum, 695011, India

Location

GSK Investigational Site

Haifa, 31096, Israel

Location

GSK Investigational Site

Jerusalem, 91031, Israel

Location

GSK Investigational Site

Petah Tikva, 49100, Israel

Location

GSK Investigational Site

Ramat Gan, 52621, Israel

Location

GSK Investigational Site

Rehovot, 76100, Israel

Location

GSK Investigational Site

Tel Aviv, 64239, Israel

Location

GSK Investigational Site

Bandar Tun Razak, Cheras, 59100, Malaysia

Location

GSK Investigational Site

Petaling Jaya, 47400, Malaysia

Location

GSK Investigational Site

Mérida, Yucatán, 97500, Mexico

Location

GSK Investigational Site

Mexico City, CP 14080, Mexico

Location

GSK Investigational Site

Islamabad, 1590, Pakistan

Location

GSK Investigational Site

Karachi, 74800, Pakistan

Location

GSK Investigational Site

Lahore, 54000, Pakistan

Location

GSK Investigational Site

Lahore, 54600, Pakistan

Location

GSK Investigational Site

Multan, 60000, Pakistan

Location

GSK Investigational Site

Lima, Lima Province, Lima 11, Peru

Location

GSK Investigational Site

Lima, Lima Province, Lima 34, Peru

Location

GSK Investigational Site

Callao, Callao 2, Peru

Location

GSK Investigational Site

Elblag, 82-300, Poland

Location

GSK Investigational Site

Kielce, 25-640, Poland

Location

GSK Investigational Site

Krakow, 31-108, Poland

Location

GSK Investigational Site

Olsztyn, 10-226, Poland

Location

GSK Investigational Site

Olsztyn, 10-228, Poland

Location

GSK Investigational Site

Warsaw, 02-781, Poland

Location

GSK Investigational Site

Moscow, 115 478, Russia

Location

GSK Investigational Site

Moscow, 117997, Russia

Location

GSK Investigational Site

Moscow, 129128, Russia

Location

GSK Investigational Site

Saint Petersburg, 197022, Russia

Location

GSK Investigational Site

Saint Petersburg, 197758, Russia

Location

GSK Investigational Site

Singapore, 169610, Singapore

Location

GSK Investigational Site

Incheon, 400-711, South Korea

Location

GSK Investigational Site

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

Location

GSK Investigational Site

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

Location

GSK Investigational Site

Suwon, Kyonggi-do, 443-721, South Korea

Location

GSK Investigational Site

Bangkok, 10330, Thailand

Location

GSK Investigational Site

Chelmsford, Essex, CM1 7ET, United Kingdom

Location

GSK Investigational Site

Manchester, Lancashire, M20 4BX, United Kingdom

Location

GSK Investigational Site

Sutton, Surrey, SM2 5PT, United Kingdom

Location

GSK Investigational Site

Birmingham, B15 2TH, United Kingdom

Location

GSK Investigational Site

Glasgow, G12 OYN, United Kingdom

Location

GSK Investigational Site

Ipswich, IP4 5PD, United Kingdom

Location

GSK Investigational Site

London, SE1 9RT, United Kingdom

Location

GSK Investigational Site

London, SW3 6JJ, United Kingdom

Location

GSK Investigational Site

Nottingham, NG5 1PB, United Kingdom

Location

GSK Investigational Site

Plymouth, PL6 8DH, United Kingdom

Location

Related Publications (2)

• Johnston SR, Gomez H, Stemmer SM, Richie M, Durante M, Pandite L, Goodman V, Slamon D. A randomized and open-label trial evaluating the addition of pazopanib to lapatinib as first-line therapy in patients with HER2-positive advanced breast cancer. Breast Cancer Res Treat. 2013 Feb;137(3):755-66. doi: 10.1007/s10549-012-2399-4. Epub 2013 Jan 3.

  PMID: 23283526 BACKGROUND

• de Jonge MJ, Hamberg P, Verweij J, Savage S, Suttle AB, Hodge J, Arumugham T, Pandite LN, Hurwitz HI. Phase I and pharmacokinetic study of pazopanib and lapatinib combination therapy in patients with advanced solid tumors. Invest New Drugs. 2013 Jun;31(3):751-9. doi: 10.1007/s10637-012-9885-8. Epub 2012 Oct 6.

  PMID: 23054212 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Interventions

pazopanib; Lapatinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

In 2008 at primary completion, study was terminated. In 2011, protocol amendment 4 (Am4), allowed continuation of treatment until PD for the 1 par. This par. completed the study per Am 4. Par. last visit occurred, the study is considered completed.

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: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2006
• First Posted: July 4, 2006
• Study Start: July 1, 2006
• Primary Completion: August 1, 2008
• Study Completion: March 1, 2015
• Last Updated: February 25, 2016
• Results First Posted: February 21, 2011

Record last verified: 2016-01

Locations

IN (7); SG (1); MY (2); RU (5); ME (2); KR (4); TH (1); US (19); PA (5); CA (3); FR (7); GB (10); HU (3); IL (6); PL (6); PE (3)