Pazopanib Plus Lapatinib Compared to Lapatinib Alone and Pazopanib Alone In Subjects With Metastatic Cervical Cancer

NCT00430781 | Completed Phase 2 Results

• 1 other identifier: VEG105281
• Study Type: interventional
• Target: 228
• Locations: 12 countries
• Sites: 57

Brief Summary

This study is being conducted to compare the efficacy and safety of pazopanib in combination with lapatinib with that of lapatinib alone or pazopanib alone in subjects with metastatic cervical cancer

Conditions

Neoplasms, Uterine Cervix; Metastatic Cervical Cancer

Keywords

pazopanib; ErB1/ErB2; lapatinib; persistent; VEGF; recurrent; metastatic cervical cancer; advanced; FIGO Stage IVB

Outcome Measures

Primary Outcomes (2)

• Progression-free Survival (PFS) in Interim Analysis

  PFS is defined as the interval between the date of randomization and the date of disease progression or death due to any cause. The study was designed to test Combination vs. Lapatinib first. The result indicated that Combination would not show improvement over Lapatinib even if followed until the final analysis and the Combination arm was terminated. The monotherapy arms continued to the final analysis. Data shown here are from this interim analysis.

  From randomization until at least 35 PFS events in pairwise comparison of the three treatment arms (Interim Analysis; up to 52.14 weeks)

• Progression-free Survival (PFS) in Final Analysis

  PFS is defined as the interval between the date of randomization and the date of disease progression or death due to any cause. This study began as a 3-arm study. The combination arm was terminated at the interim analysis. The monotherapy arms continued to final analysis. Data shown here are from the final analysis.

  From Randomization until 105 total PFS events in combined population of two monotherapy arms (up to 85.57 weeks)

Secondary Outcomes (6)

• Overall Survival

  From Randomization (11 December 2006) until approximately 78% overall survival events at the time of the second overall survival update (3 March 2010) (up to 168.29 weeks)

• Clinical Benefit Response

  From Randomization until 105 total PFS events in combined population of two monotherapy arms (up to 85.57 weeks)

• Response

  From Randomization until 105 total PFS events in combined population of two monotherapy arms (up to 85.57 weeks)

• Time to Response

  From Randomization until 105 total PFS events in combined population of two monotherapy arms (up to 85.57 weeks)

• Duration of Response

  From Randomization until 105 total PFS events in combined population of two monotherapy arms (up to 85.57 weeks)

Study Arms (3)

Combination arm

EXPERIMENTAL

Pazopanib plus lapatinib

Drug: lapatinib (GW572016)

Lapatinib monotherapy

ACTIVE COMPARATOR

Lapatinib

Drug: lapatinib (GW572016)

Pazopanib monotherapy

ACTIVE COMPARATOR

Pazopanib

Drug: pazopanib (GW786034)

Interventions

pazopanib (GW786034) DRUG

Pazopanib monotherapy

lapatinib (GW572016) DRUG

Combination arm; Lapatinib monotherapy

Eligibility Criteria

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

You may qualify if:

• Signed, written informed consent prior to performing any study-related procedures
• Female subjects ≥18 years of age
• FIGO Stage IVB, or recurrent or persistent cervical cancer
• Life expectancy of at least 12 weeks
• ECOG status of 0 or 1.
• Histologically confirmed FIGO Stage IVB, or recurrent or persistent squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix which is not amenable to curative treatment with surgery and/or radiation therapy
• Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded). Each lesion must be ≥ 20 mm when measured by conventional techniques, including palpitation, plain x-ray, CT and MRI, or ≥10 mm when measured by spiral CT.
• At least one "target lesion" to be used to assess response as defined by Response Evaluation Criteria in Solid Tumors (RECIST; Terasse, 2000). Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy.
• Received 0 or 1 prior chemotherapy regimen for metastatic disease.
• Note: Chemotherapy given in combination with radiation therapy as a radiosensitizer does not count toward this prior therapy limit
• Recovered from the effects of surgery or chemotherapy. At least three weeks must have elapsed from the last administration of chemotherapy.
• Adequate organ and bone marrow function as defined in Table 1.
• Table 1:(Definitions for Adequate Organ Function)
• System:(Laboratory Values)
• Hematologic: Absolute neutrophil count (ANC)(≥ 1.5 X 109/L)Hemoglobin1(≥9 g/dL)Platelets(≥100 X 109/L)

You may not qualify if:

• Neuroendocrine or small cell carcinoma of the cervix.
• Prior use of any biologic therapy with VEGF, VEGFR, or ErbB1/ErbB2 inhibitors.
• 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 28 days or 5 half-lives, whichever is longer, preceding the first dose of study medication.
• Has taken or is taking prohibited medications listed in the protocol.
• Any serious and/or unstable pre-existing medical, psychiatric, or other conditions that could interfere with patient's safety, obtaining informed consent or compliance to the study.
• History of another malignancy. Note: Patients who have had another malignancy and have been disease-free for 5 years, or patients with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible.
• History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis. Routine screening with CNS imaging studies (computed tomography \[CT\] or magnetic resonance imaging \[MRI\]) is required only if clinically indicated.
• 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.
• Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib.
• Corrected QT interval (QTc) prolongation defined as QTc interval \> 470 msecs.
• History of any one of the following cardiac conditions within the past 6 months:

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (63)

GSK Investigational Site

Los Angeles, California, 90033, United States

Location

GSK Investigational Site

Orange, California, 92868, United States

Location

GSK Investigational Site

Stanford, California, 94305-5317, United States

Location

GSK Investigational Site

Augusta, Georgia, 30912, United States

Location

GSK Investigational Site

Boston, Massachusetts, 02115, United States

Location

GSK Investigational Site

Albuquerque, New Mexico, 87131-5276, United States

Location

GSK Investigational Site

New York, New York, 10016, United States

Location

GSK Investigational Site

Cleveland, Ohio, 44106, United States

Location

GSK Investigational Site

Columbus, Ohio, 43214, United States

Location

GSK Investigational Site

Oklahoma City, Oklahoma, 73104, United States

Location

GSK Investigational Site

Chattanooga, Tennessee, 37403, United States

Location

GSK Investigational Site

Dallas, Texas, 75390, United States

Location

GSK Investigational Site

Capital Federal, Buenos Aires, C1405CUB, Argentina

Location

GSK Investigational Site

Ciudad Autonoma de Buenos Aires, Buenos Aires, C1185AAT, Argentina

Location

GSK Investigational Site

Neuquén, Neuquén Province, Q8300HDH, Argentina

Location

GSK Investigational Site

Rosario, Santa Fe Province, S2000KZE, Argentina

Location

GSK Investigational Site

Santa Fe, Santa Fe Province, 3000, Argentina

Location

GSK Investigational Site

San Miguel de Tucumán, Tucumán Province, 4000, Argentina

Location

GSK Investigational Site

Quilmes, 1878, Argentina

Location

GSK Investigational Site

Brussels, 1000, Belgium

Location

GSK Investigational Site

Brussels, 1200, Belgium

Location

GSK Investigational Site

Ghent, 9000, Belgium

Location

GSK Investigational Site

Leuven, 3000, Belgium

Location

GSK Investigational Site

Roeselare, 8800, Belgium

Location

GSK Investigational Site

Calgary, Alberta, T2N 4N2, Canada

Location

GSK Investigational Site

Vancouver, British Columbia, V5Z 4E6, Canada

Location

GSK Investigational Site

Hamilton, Ontario, L8V 5C2, Canada

Location

GSK Investigational Site

Toronto, Ontario, M5G 2M9, Canada

Location

GSK Investigational Site

Montreal, Quebec, H2L 4M1, Canada

Location

GSK Investigational Site

Tallinn, 11619, Estonia

Location

GSK Investigational Site

Tartu, 51003, Estonia

Location

GSK Investigational Site

Bordeaux, 33076, France

Location

GSK Investigational Site

Caen, 14076, France

Location

GSK Investigational Site

Lille, 59020, France

Location

GSK Investigational Site

Marseille, 13273, France

Location

GSK Investigational Site

Strasbourg, 67085, France

Location

GSK Investigational Site

Villejuif, 94805, France

Location

GSK Investigational Site

Munich, Bavaria, 80337, Germany

Location

GSK Investigational Site

Saarbrücken, Saarland, 66113, Germany

Location

GSK Investigational Site

Halle, Saxony-Anhalt, 06120, Germany

Location

GSK Investigational Site

Magdeburg, Saxony-Anhalt, 39108, Germany

Location

GSK Investigational Site

Berlin, State of Berlin, 10117, Germany

Location

GSK Investigational Site

Berlin, State of Berlin, 10367, Germany

Location

GSK Investigational Site

Ahemdabad, 380016, India

Location

GSK Investigational Site

Mangalore, 575001, India

Location

GSK Investigational Site

New Delhi, 110096, India

Location

GSK Investigational Site

Trivandrum, 695011, India

Location

GSK Investigational Site

Cork, Ireland

Location

GSK Investigational Site

Dublin, 7, Ireland

Location

GSK Investigational Site

Bari, Apulia, 70124, Italy

Location

GSK Investigational Site

Napoli, Campania, 80131, Italy

Location

GSK Investigational Site

Milan, Lombardy, 20141, Italy

Location

GSK Investigational Site

Campobasso, Molise, 86100, Italy

Location

GSK Investigational Site

Mexico City, CP 14080, Mexico

Location

GSK Investigational Site

Barcelona, 08036, Spain

Location

GSK Investigational Site

Barcelona, 08907, Spain

Location

GSK Investigational Site

La Laguna (Santa Cruz de Tenerife), 38320, Spain

Location

GSK Investigational Site

Madrid, 28007, Spain

Location

GSK Investigational Site

Marid, 28040, Spain

Location

GSK Investigational Site

Pamplona, 31008, Spain

Location

GSK Investigational Site

Bangkok, 10330, Thailand

Location

GSK Investigational Site

Chiang Mai, 50200, Thailand

Location

GSK Investigational Site

Khon Kaen, 40002, Thailand

Location

Related Publications (3)

• Monk BJ, Mas Lopez L, Zarba JJ, Oaknin A, Tarpin C, Termrungruanglert W, Alber JA, Ding J, Stutts MW, Pandite LN. Phase II, open-label study of pazopanib or lapatinib monotherapy compared with pazopanib plus lapatinib combination therapy in patients with advanced and recurrent cervical cancer. J Clin Oncol. 2010 Aug 1;28(22):3562-9. doi: 10.1200/JCO.2009.26.9571. Epub 2010 Jul 6.

  PMID: 20606083 RESULT

• Monk BJ, Pandite LN. Survival data from a phase II, open-label study of pazopanib or lapatinib monotherapy in patients with advanced and recurrent cervical cancer. J Clin Oncol. 2011 Dec 20;29(36):4845. doi: 10.1200/JCO.2011.38.8777. Epub 2011 Nov 14. No abstract available.

  PMID: 22084371 RESULT

• 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

Neoplasms; Uterine Cervical Neoplasms; Recurrence

Interventions

pazopanib; Lapatinib

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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

Study Record Dates

• First Submitted: January 31, 2007
• First Posted: February 2, 2007
• Study Start: November 1, 2006
• Primary Completion: July 1, 2008
• Study Completion: July 1, 2011
• Last Updated: May 8, 2015
• Results First Posted: March 14, 2011

Record last verified: 2015-04

Locations

IE (2); TH (3); AR (7); CA (5); US (12); ES (2); IT (4); DE (6); BE (5); IN (4); ME (1); FR (6)