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Neoplasms, Head and NeckPhase 2NCT00725764

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

A Phase 2 study testing GSK1363089 (foretinib) in people with Neoplasms, Head and Neck, run by GlaxoSmithKline at 11 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Neoplasms, Head and Neck
What is being tested?
GSK1363089 (foretinib)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
14 participants
Where
11 sitesUnited States
Study dates
27 Aug 2007to 2 May 2009
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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).

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

United States11 sites

  • GSK Investigational Site

    Atlanta, Georgia, 30309

  • GSK Investigational Site

    Charleston, South Carolina, 29403

  • GSK Investigational Site

    Chicago, Illinois, 60637

  • GSK Investigational Site

    Houston, Texas, 77030

  • GSK Investigational Site

    Indianapolis, Indiana, 46254

  • GSK Investigational Site

    Lebanon, New Hampshire, 03756

  • GSK Investigational Site

    Minneapolis, Minnesota, 55407-3799

  • GSK Investigational Site

    Morgantown, West Virginia, 28506

  • GSK Investigational Site

    Nashville, Tennessee, 37203

  • GSK Investigational Site

    San Antonio, Texas, 78229

  • GSK Investigational Site

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: A Phase 2 Study of the MET RTK Inhibitor GSK1363089 (Formerly XL880) in Subjects With Recurrent or Metastatic Squamous Cell Cancer of the Head and Neck

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.

Being tested
GSK1363089 (foretinib)
Keywords
VEGFR2, XL880, foretinib, Squamous Cell Cancer of the Head and Neck, MET, GSK1363089
Medical subject headings
Head and Neck Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GSK1363089 (foretinib)Drug

    Also called GSK1363089 (formerly XL880)

    Multitargeted tyrosine kinase inhibitor

Study groups in NCT00725764
Study groupRoleWhat they receive
Single ArmExperimentalParticipants who qualified for study entry received 240 mg of GSK1363089 (foretinib) on a 5-day on 9-day off schedule every 2 weeks.
Receives: Drug: GSK1363089 (foretinib)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Approximately up to 1 year

  2. 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.

    Measured: Approximately up to 1 year

  3. 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.

    Measured: Up to 20 months

  4. 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.

    Measured: Up to 20 months

  5. 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.

    Measured: Week 5 [Day 29]

Secondary outcomes (10)

  1. Duration of Progression-free Survival

    Progression-free survival was defined as the duration from the date of first dose to the date of disease progression or date of death without documented progression or date of study termination + 1. The start of confounding anticancer therapy was not treated as a censoring event. Time to progression or death was censored at the study termination date or at the analysis cutoff date, if earlier.

    Measured: Approximately up to 1 year

  2. Duration of Overall Survival

    Overall survival was defined as the duration from the date of the first dose to the date of death. The start of a confounding anticancer therapy was treated as a censoring event. Every effort made to follow participant's until death. Time to death was censored at the date of the latest participant contact or at the analysis cutoff date, if earlier. Kaplan-Meier method was used to estimate the overall survival distribution.

    Measured: Approximately up to 1 year

  3. Duration of Stable Disease

    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. Duration of stable disease was defined as the time between the date of first dose of study drug and the first occurrence of 1 of the events: Tumor progression per RECIST as assessed by the investigator, Termination of study drug because of disease progression, Death due to disease progression, Disease progression as documented on the participant follow-up status form, Initiation of subsequent anticancer therapy.

    Measured: Approximately up to 1 year

  4. Percentage Participants With Disease Stabilization Rate

    Disease stabilization rate was defined as the proportion of participants for whom the best overall response was a PR, CR, or stable disease. percentage participants with disease stabilization rate were presented.

    Measured: Approximately up to 1 year

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

    Plasma samples for pharmacokinetic analysis were planned to be drawn at time points: Day 1, 5, 19, 33, 43, 47 (approximately 15 minutes before dosing, and at 4 hours (±30 minutes) after dosing) of each treatment cycle, however these analyses were not completed. Cmax was defined as maximal measured plasma concentration over the time span specified. Data was not collected for this endpoint.

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

  6. Time to Maximum Plasma Concentration (Tmax) of Foretinib in Participants With SCCHN

    tmax was defined as the time to the maximum or "peak" concentration of a drug observed after multiple administration. Blood samples were planned to be obtained during the time points: Day 1, 5, 19, 33, 43, 47 (approximately 15 minutes before dosing, and at 4 hours (±30 minutes) after dosing). However these analyses were not completed. Data was not collected for this endpoint.

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

  7. Area Under the Concentration-time Curve (AUC) of Foretinib in Participants With SCCHN

    AUC was defined as area under the plasma concentration vs. time curve. Blood samples were planned to be collected on time points: Day 1, 5, 19, 33, 43, 47 (approximately 15 minutes before dosing, and at 4 hours (±30 minutes) after dosing). However these analyses were not completed. Data was not collected for this endpoint.

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

  8. Elimination Half-life (t1/2) of Foretinib in Participants With SCCHN

    t1/2 was defined as the time to when half of the total amount of a particular substance is eliminated from the body. Blood samples were planned to be obtained during indicated time points: Day 1, 5, 19, 33, 43, 47 (approximately 15 minutes before dosing, and at 4 hours (±30 minutes) after dosing). However these analyses were not completed. Data was not collected for this endpoint.

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

  9. Apparent Oral Clearance

    Blood samples were planned to be obtained during indicated time points: Day 1, 5, 19, 33, 43, 47 (approximately 15 minutes before dosing, and at 4 hours (±30 minutes) after dosing). Data for apparent oral clearance was not derived as pharmacokinetic analysis was not completed. Data was not collected for this endpoint.

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

  10. Apparent Volume of Distribution

    Blood samples were planned to be obtained during indicated time points: Day 1, 5, 19, 33, 43, 47 (approximately 15 minutes before dosing, and at 4 hours (±30 minutes) after dosing). Data for apparent volume of distribution was not derived as pharmacokinetic analysis was not completed. Data was not collected for PK analysis.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Jul 2008 (estimated)
  2. Study start27 Aug 2007
  3. Primary completion2 May 2009
  4. Study completion2 May 2009

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
14 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00725764
Sponsor's protocol ID
MET111646
Status last verified
Jul 2017
First submitted
28 Jul 2008
Last updated
16 Oct 2017
Data monitoring committee
No
Individual data sharing
Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing GSK1363089 (foretinib) in people with Neoplasms, Head and Neck, run by GlaxoSmithKline at 11 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Oct 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Achieving Best Overall Response (time frame: Approximately up to 1 year). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00725764.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2017.

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