Part A: Radiolabel Study With GW786034 Part B: Single Dose of GW786034

NCT00478725 | Completed Phase 1

• 1 other identifier: VEG10004
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief Summary

To study the absorption, distribution, metabolism and excretion of GW786034, and the absorption of a single IV dose of GW786034

Conditions

Carcinoma, Renal Cell

Keywords

Metastatic Cancer; Advanced Cancer

Outcome Measures

Primary Outcomes (2)

• Part A: excretion of radioactivity

  over 168 hrs

• Part B: Plasma pazopanib, clearance (CL) and AUC(0-t), AUC(0-8),Cmax and half-life (t1/2) pazopanib and pazopanib metabolites (GSK 1268992, GSK1268997, GSK1071306 and GW700201)

  over 48 hrs

Secondary Outcomes (8)

• Part A: Blood and plasma total radioactivity AUC(0-t), AUC(0-8),Cmax and t1/2

  over 168 hrs.

• Part B: Safety parameters

  over 48 hrs.

• Blood and plasma total radioactivity AUC(0-t), AUC(0-∞), Cmax and t1/2 following oral administration of 400 mg of [14C]-pazopanib containing approximately 70 µCi of radioactivity.

  on Day 15 of Cycle 1.

• Samples (for use in a separate study) to characterize and quantify metabolites of pazopanib in plasma, urine and feces.

  on Day 15 of Cycle 1.

• Blood:plasma ratio of total drug-related material (radioactivity).

  on Day 15 of Cycle 1.

Study Arms (2)

Part A

EXPERIMENTAL

Absorption, Distribution, Metabolism and Elimination of a Single Oral \[14C\] Labeled Dose of GW786034

Drug: GW786034, oral; Drug: GW786034, radiolabeled oral

Part B

EXPERIMENTAL

characterize the pharmacokinetics of a single IV dose of GW786034

Drug: GW786034, oral; Drug: GW786034, IV

Interventions

GW786034, oral DRUG

oral, 800 mg

Also known as: GW786034, pazopanib

Part A; Part B

GW786034, IV DRUG

IV, 5 mg

Also known as: GW786034, pazopanib

Part B

GW786034, radiolabeled oral DRUG

oral, 400 mg radiolabeled

Also known as: GW786034, pazopanib

Part A

Eligibility Criteria

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

You may qualify if:

• Subject 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 subject'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.
• Has histologically or cytologically confirmed advanced solid tumor malignancy.
• For Part A: Males, age: 30 years or greater.
• For Part B: Males or Females, age: 18 years or greater.
• For Part A or B, males that meet the following criteria.
• A male subject with a female partner of childbearing potential is eligible to enter and participate in this study if he:
• Agrees to use double-barrier contraception (condom with spermicidal jelly, foam, suppository or film, or a condom and his partner uses a diaphragm with spermicide), OR
• Agrees to complete abstinence from sexual intercourse for 14 days before exposure to investigational product, through the clinical trial, and for at least 21 days after the last dose of investigational product.
• For Part B, females that meet the following criteria:
• A female subject 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 (total cessation of menses for \>/ 1 year), OR

You may not qualify if:

• 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 6 months prior to beginning study treatment. Screening with CNS imaging studies (CT scan or MRI) is required only if clinically indicated or if the subject has a history of CNS metastases.
• Clinically significant gastrointestinal (GI) abnormalities including, but not limited to: malabsorption syndrome, history of resection of the stomach or small bowel, active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis or other conditions that increase the risk for perforation, history of abdominal fistula, GI perforation or intra-abdominal abscess within 4 weeks prior to beginning study treatment.
• Presence of uncontrolled infection.
• Corrected QT interval (QTc) \> 480 msec.
• History of any one or more of the following cardiovascular conditions within the past 6 months: congestive heart failure, cardiac angioplasty or stenting, myocardial infarction, unstable angina OR symptomatic peripheral vascular disease.
• Has poorly controlled hypertension (systolic blood pressure \[SBP\] \>/ 140 mmHg, or diastolic blood pressure \[DBP\] \>/ 90 mmHg).
• Note: Initiation or adjustment of anti-hypertensive medication(s) is permitted prior to study entry. The blood pressure (BP) must be re-assessed on 2 occasions that are separated by a minimum of 24 hours. The mean SBP/DBP values from both BP assessments must be \< 140/90 mmHg in order for a subject to be eligible for the study.
• History of cerebrovascular accident or pulmonary embolism within the past 6 months.
• History of untreated deep venous thrombosis (DVT) within the past 6 months.
• Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible.
• Prior major surgery or trauma within the past 28 days or presence of any wound, fracture or ulcer which is not fully healed.
• Evidence of active bleeding, bleeding diathesis or hemoptysis within 6 weeks prior to study treatment.
• Use of prohibited medications within the timeframes specified in Section 9.2, Prohibited Medications of the protocol.
• Use of an investigational agent, including an investigational anti-cancer agent within 28 days or 5 half-lives, whichever is longer, preceding the first dose of pazopanib.
• Treatment with any cancer therapy (including chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy, surgery or tumor embolization) within 14 days prior to the first dose of pazopanib.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (2)

GSK Investigational Site

Minneapolis, Minnesota, 55404, United States

Location

GSK Investigational Site

Nashville, Tennessee, 37203, United States

Location

Related Publications (1)

• Deng Y, Sychterz C, Suttle AB, Dar MM, Bershas D, Negash K, Qian Y, Chen EP, Gorycki PD, Ho MY. Bioavailability, metabolism and disposition of oral pazopanib in patients with advanced cancer. Xenobiotica. 2013 May;43(5):443-53. doi: 10.3109/00498254.2012.734642. Epub 2012 Nov 16.

  PMID: 23548165 BACKGROUND

Related Links

• Results for study VEG10004 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Carcinoma, Renal Cell; Neoplasm Metastasis

Interventions

pazopanib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2007
• First Posted: May 25, 2007
• Study Start: July 18, 2007
• Primary Completion: July 1, 2008
• Study Completion: July 1, 2008
• Last Updated: November 17, 2017

Record last verified: 2017-11

Locations

US (2)