Phase 2 Study of GSK1363089 (Formerly XL880) in Adults With Squamous Cell Cancer of the Head and Neck

NCT00725764 | Completed Phase 2 Results

• 1 other identifier: MET111646
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 11

Brief Summary

This study is being conducted to determine the best confirmed response rate, safety, and tolerability of GSK1363089 treatment in adult subjects with squamous cell carcinoma of the head and neck (SCCHN). GSK1363089 is a new chemical entity that inhibits multiple receptor tyrosine kinases (RTKs) with growth-promoting and angiogenic properties. The primary targets of GSK1363089 are the HGF and vascular endothelial growth factor (VEGF) RTK families (eg, MET, VEGFR2/kinase insert domain receptor \[KDR\]). Since MET overexpression has been associated with poorer prognosis and MET tyrosine kinase mutations have been reported in SCCHN, inhibition of MET receptor and VEGFR2/KDR activation by agents such as GSK1363089 may be of therapeutic benefit in this patient population.

Conditions

Neoplasms, Head and Neck

Keywords

VEGFR2; XL880; foretinib; Squamous Cell Cancer of the Head and Neck; MET; GSK1363089

Outcome Measures

Primary Outcomes (5)

• Number of Participants Achieving Best Overall Response

  Best overall response was assessed by the investigator per response evaluation criteria in solid tumors (RECIST). Per RECIST v1.0 for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Tumor size was recorded at Baseline, and tumor response were recorded approximately every 8 weeks. Tumor response were classified by the investigator using RECIST criteria participant's best response whether observed in the study treatment period or the treatment extension period was considered. The best overall response was the best response recorded from the start of treatment until disease progression/recurrence. Number of participants who achieved best overall response were recorded.

  Approximately up to 1 year

• Percentage of Participants With Objective Response Rate (ORR)

  ORR was defined as the proportion of participants achieving best overall response of confirmed CR or PR divided by the total number of participants who received treatment. Per RECIST v1.0 for target lesions and assessed by MRI: CR, Disappearance of all target lesions; Partial Response PR, \>=30% decrease in the sum of the longest diameter of target lesions; OR = CR + PR. Participants were evaluated for tumor response per RECIST. Percentage of participants with ORR were reported.

  Approximately up to 1 year

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Data for number of participants who presented one or more adverse events (serious or non serious) was reported. An AE was defined as any untoward medical occurrence (MO) in a participant temporally associated with the use of a medicinal product (MP), whether or not considered related to the MP and can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with its use. The SAE was any untoward MO that, at any dose, results in death, life threatening, persistent or significant disability/incapacity, results in or prolongs inpatient hospitalization, congenital abnormality or birth defect, that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition.

  Up to 20 months

• Number of Participants With Abnormalities of Common Toxicity Criteria for Adverse Events (CTCAE) Grade 3 in Laboratory Parameters (Clinical Chemistry and Hematology)

  The National Cancer Institute -CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each toxicity based on the following general guideline: Grade 1: Mild AE, Grade 2: Moderate AE, Grade 3: Severe AE, Grade 4: Life-threatening or disabling AE and Grade 5: Death related to AE. Number of participants with abnormalities of CTCAE grade 3 in clinical chemistry parameters: alanine aminotransferase (ALT), γ-glutamyl transferase (GGT), phosphate, low sodium and hematology parameters: Leukocyte and Lymphocytes were presented.

  Up to 20 months

• Number of Participants With Abnormalities in Urinalysis

  Urinalysis parameters like appearance, color, pH, specific gravity, ketones, protein, glucose, bilirubin, nitrite, urobilinogen, and occult blood were performed. Number of participants with abnormalities are reported. In case of no abnormalities observed then it is reported as zero.

  Week 5 [Day 29]

Secondary Outcomes (10)

• Duration of Progression-free Survival

  Approximately up to 1 year

• Duration of Overall Survival

  Approximately up to 1 year

• Duration of Stable Disease

  Approximately up to 1 year

• Percentage Participants With Disease Stabilization Rate

  Approximately up to 1 year

• Maximum Plasma Concentration (Cmax) of Foretinib in Participants With Squamous Cell Carcinoma of the Head and Neck (SCCHN)

  Day 1, 5, 19, 33, 43, 47 (pre-dose15 min) and 4 h (± 30 min) post-dose

Study Arms (1)

Single Arm

EXPERIMENTAL

Participants who qualified for study entry received 240 mg of GSK1363089 (foretinib) on a 5-day on 9-day off schedule every 2 weeks.

Drug: GSK1363089 (foretinib)

Interventions

GSK1363089 (foretinib) DRUG

Multitargeted tyrosine kinase inhibitor

Also known as: GSK1363089 (formerly XL880)

Single Arm

Eligibility Criteria

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

You may qualify if:

• The subject has a histologically or cytologically confirmed diagnosis of SCCHN and
• has recurrent and/or metastatic disease
• is not eligible for curative intent surgery or radiotherapy
• has no history of uncontrolled tumor bleeding including hemoptysis in patients with documented pulmonary metastasis.
• The subject has measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as =20 mm with conventional techniques, or as =10 mm with spiral computerized tomography (CT) scan.
• Subject is capable of swallowing capsules.
• Fifteen unstained slides of tumor tissue, archival or fresh, or paraffin block are available, and there - confirmation that samples have been sent for analysis at the central laboratory.
• The subject is at least 18 years old.
• The subject has an Eastern Cooperative Oncology Group (ECOG) performance status =1.
• In the adrenocorticotropic hormone (ACTH) stimulation test, the subject has a serum cortisol level =20 µg/dL (552 nmol/L) 30-90 minutes after injection of ACTH.
• The subject has organ and marrow function as follows: absolute neutrophil count (ANC) =1500/mm3, platelets =100,000/mm3, hemoglobin =9 g/dL, bilirubin =1.5 mg/dL, serum creatinine =1.5 mg/dL and/or calculated creatinine clearance =60 mL/min, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =2.5 times the upper limit of normal if no liver involvement or =5 times the upper limit of normal with liver involvement.
• The subject has signed the informed consent document.
• Sexually active subjects must use a medically accepted method of contraception during the course of the study.
• Female patients of childbearing potential must have a negative pregnancy test at enrollment.
• The subject has had no other diagnosis of malignancy (unless non-melanoma skin cancer, in situ carcinoma of the cervix, or a malignancy diagnosed =5 years ago, and has had no evidence of disease for 5 years prior to screening for this study).

You may not qualify if:

• The subject has received radiation to \>25% of his or her bone marrow within 30 days of GSK1363089 treatment.
• The subject has received an investigational drug within 30 days (or \<5.5 half lives) of the first dose of study drug.
• The subject has received more than one regimen of systemic anticancer therapy for disease that has recurred or is metastatic. This may include either single-agent or combination cytotoxic chemotherapy with radiotherapy or anti-EGFR treatment (eg, cetuximab). Adjuvant or neoadjuvant systemic chemotherapy does not count as a regimen for recurrent or metastatic disease.
• The subject has progressed within 6 months after completion of curative intent (definitive) treatment for localized/locoregionally advanced disease.
• The subject has not recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0 Grade =1 from adverse events (AEs) due to investigational drugs or other medications that were administered more than 30 days before study enrollment with the sole exception of persistent Grade 2 peripheral neuropathy in patients who have previously received platinum-based therapy.
• The subject has known brain metastases.
• The subject has uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, active alcoholism, or psychiatric illness that would limit compliance with study requirements.
• The subject is pregnant or breastfeeding.
• The subject is known to be positive for the human immunodeficiency virus (HIV).
• The subject has an allergy or hypersensitivity to components of the GSK1363089 formulation.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (11)

GSK Investigational Site

Atlanta, Georgia, 30309, United States

Location

GSK Investigational Site

Chicago, Illinois, 60637, United States

Location

GSK Investigational Site

Indianapolis, Indiana, 46254, United States

Location

GSK Investigational Site

Minneapolis, Minnesota, 55407-3799, United States

Location

GSK Investigational Site

St Louis, Missouri, 63110, United States

Location

GSK Investigational Site

Lebanon, New Hampshire, 03756, United States

Location

GSK Investigational Site

Charleston, South Carolina, 29403, United States

Location

GSK Investigational Site

Nashville, Tennessee, 37203, United States

Location

GSK Investigational Site

Houston, Texas, 77030, United States

Location

GSK Investigational Site

San Antonio, Texas, 78229, United States

Location

GSK Investigational Site

Morgantown, West Virginia, 28506, United States

Location

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Head and Neck Neoplasms

Interventions

GSK 1363089

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2008
• First Posted: July 30, 2008
• Study Start: August 27, 2007
• Primary Completion: May 2, 2009
• Study Completion: May 2, 2009
• Last Updated: October 16, 2017
• Results First Posted: October 16, 2017

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will share

Locations

US (11)