Lip and Oral Cavity Squamous Cell CarcinomaPhase 2NCT01414426
Vandetanib in Preventing Head and Neck Cancer in Patients With Precancerous Head and Neck Lesions
A Phase 2 study testing vandetanib, immunohistochemistry staining method and laboratory biomarker analysis in people with Lip and Oral Cavity Squamous Cell Carcinoma and Oral Cavity Verrucous Carcinoma, run by University of Chicago at 1 site in United States.
Trial summary
This randomized phase II trial studies how well vandetanib works in preventing head and neck cancer in patients with precancerous head and neck lesions. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of vandetanib may keep cancer from forming in patients with premalignant lesions Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lip and Oral Cavity Squamous Cell Carcinoma, Oral Cavity Verrucous Carcinoma, Precancerous Condition
- What is being tested?
- vandetanib, immunohistochemistry staining method and laboratory biomarker analysis
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2012to 1 Jun 2019
- 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
- Histological/cytological confirmation of oral cavity dysplasia and one of three additional criteria:
- Prior history of OSCC
- Loss of heterozygosity (LOH) at 3p or 9p
- Expression by immunohistochemistry (IHC) of budding uninhibited by benzimidazoles 3 (BUB3)/sex determining region Y (SOX4)
- Provision of informed consent
- Females of child bearing age must have a negative serum pregnancy test within 7 days of first dose of study drug
- Patients must not have been taking steroids or are on a stable dose of steroids for at least 14 days before enrollment
- Patients must have a Karnofsky Performance Score of 70% or above
Who cannot join
- History of malignancy within the last 5 years other than squamous cell carcinoma of the head and neck (SCCHN) and superficial non-melanoma skin cancer; patients with a history of SCCHN must be free of active carcinoma
- Currently receiving treatment for any malignancy
- Serum bilirubin > 1.5x the upper limit of reference range (ULRR)
- Creatinine clearance =< 30 mL/minute (calculated by Cockcroft-Gault formula)
- Potassium, < 4.0 mmol/L despite supplementation; or above the Common Terminology Criteria for Adverse Events (CTCAE) grade 1 upper limit
- Magnesium below the normal range despite supplementation, or above the CTCAE grade 1 upper limit
Show all 25Show fewer
- Serum calcium above the CTCAE grade 1 upper limit; in cases where the serum calcium is below the normal range, 2 options would be available: 1) the calcium adjusted for albumin is to be obtained and substituted for the measured serum value; exclusion is to then be based on the adjusted for albumin values falling below the normal limit; 2) Determine the ionized calcium levels; if these ionized calcium levels are out of normal range despite supplementation, then the patient must be excluded
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 × ULRR
- Alkaline phosphatase (ALP) > 2.5 x ULRR
- Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the Investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol
- Clinically significant cardiovascular event (e.g. myocardial infarction, superior vena cava syndrome [SVC], New York Heart Association [NYHA] classification of heart disease > 2 within 3 months before entry; or presence of cardiac disease that, in the opinion of the Investigator, increases the risk of ventricular arrhythmia
- History of arrhythmia (multifocal premature ventricular contractions (PVCs), bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation), which is symptomatic or requires treatment (CTCAE grade 3) or asymptomatic sustained ventricular tachycardia; atrial fibrillation, controlled on medication is not excluded
- QTc prolongation with other medications that required discontinuation of that medication
- Congenital long QT syndrome or 1st degree relative with unexplained sudden death under 40 years of age
- Presence of left bundle branch block (LBBB)
- QTc with Bazett's correction that is unmeasurable or ≥450 msec on screening electrocardiogram (ECG); (Note: If a subject has a QTc interval >= 450 msec on screening ECG, the screen ECG may be repeated twice [at least 24 hours apart]; the average QTc from the three screening ECGs must be < 450 msec in order for the subject to be eligible for the study)
- Any concurrent medication with a known risk of inducing Torsades de Pointes, that in the investigator's opinion cannot be discontinued
- Concomitant medications that are potent inducers (rifampicin, rifabutin, phenytoin, carbamazepine, phenobarbital and St. John's Wort) of Cytochrome P450 3A4 (CYP3A4) function
- Hypertension not controlled by medical therapy (systolic blood pressure greater than 160 mm mercury (Hg) or diastolic blood pressure greater than 100 mm Hg)
- Currently active diarrhea that may affect the ability of the patient to absorb the ZD6474 or tolerate diarrhea
- Women who are currently pregnant or breast-feeding
- Receipt of any investigational agents within 30 days prior to commencing study treatment
- Previous enrollment or randomization of treatment in the present study
- Major surgery within 4 weeks or incompletely healed surgical incision before starting study therapy
- Involvement in the planning and conduct of the study (applies to both Astra Zeneca staff and staff at the study site)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomized Placebo- Controlled Pilot Study of ZD6474 as a Chemopreventive Agent for Premalignant Lesions of the Head and Neck
This randomized phase II trial studies how well vandetanib works in preventing head and neck cancer in patients with precancerous head and neck lesions. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of vandetanib may keep cancer from forming in patients with premalignant lesions
Read the detailed description
PRIMARY OBJECTIVE:
- Determine the effect of ZD6474 (vandetanib) compared to placebo on microvessel density (MVD) from baseline to 3 months in patients at risk for oral squamous cell carcinoma (OSCC) with preneoplastic lesions.
SECONDARY OBJECTIVES:
- Change in MVD over 6 months. II. Change in putative targets of ZD6474: tissues will be analyzed by immunohistochemistry (IHC) for phosphorylated epidermal growth factor receptor (pEGFR), EGFR, phosphorylated-vascular endothelial growth factor receptor 2 (pVEGFR2), VEGFR2.
III. Change in proliferative index as measured by Ki-67 IHC. IV. Safety, tolerability, and adherence to ZD6474 for 6 months in patients at risk for OSCC.
TERTIARY OBJECTIVES:
- Compare OSCC incidence in both study arms (ZD6474 and placebo).
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive vandetanib orally (PO) once daily (QD) for 6 months. Treatment continues in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive placebo PO QD for 6 months. Treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 9 and 12 months and then every 6 months for 2 years.
- Conditions
- Lip and Oral Cavity Squamous Cell Carcinoma, Oral Cavity Verrucous Carcinoma, Precancerous Condition
- Being tested
- vandetanib, placebo, immunohistochemistry staining method, laboratory biomarker analysis, biopsy
- Medical subject headings
- Lymphoid Interstitial Pneumonia, Squamous Cell Carcinoma of Head and Neck, Precancerous Conditions
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
vandetanibDrug
Also called AZD6474, ZD6474
Given PO
placeboOther
Also called PLCB
Given PO
immunohistochemistry staining methodOther
Also called immunohistochemistry
Correlative studies
laboratory biomarker analysisOther
Correlative studies
biopsyProcedure or surgery
Also called biopsies
Correlative studies
Also called pharmacological studies
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Arm I (chemoprevention) | Experimental | Patients receive vandetanib PO QD for 6 months. Treatment continues in the absence of disease progression or unacceptable toxicity. Receives: Drug: vandetanib; Other: immunohistochemistry staining method; Other: laboratory biomarker analysis; Procedure: biopsy; Other: pharmacological study |
| Arm II (placebo) | Placebo comparator | Patients receive placebo PO QD for 6 months. Treatment continues in the absence of disease progression or unacceptable toxicity. Receives: Other: placebo; Other: immunohistochemistry staining method; Other: laboratory biomarker analysis; Procedure: biopsy; Other: pharmacological study |
What is being measured
The primary outcome is the main question the study is designed to answer.
Comparison Between Treatment Groups of the Within-patient Change in MVD Score Following Treatment Initiation
A Wilcoxon ranksum test may be used if the normality assumption is not satisfied. Alternatively, change in MVD may be transformed (e.g. log-transformation) to satisfy the normality assumption. Additional analyses will include linear regression models with treatment effect and other prognostic factors as covariates.
Measured: Baseline to 3 months
Secondary outcomes (4)
Number of Participants With Adverse Events
Adverse events rate shows the total number of subjects with an AE.
Measured: Weekly during treatment, up to week 24
Number of Participants Who Adhered to Treatment
Number of participants who Adhered to Treatment
Measured: Over 6 months
Development of Oral and Other Cancers
Number of patients with new cancer
Measured: At 6, 9, and 12 months and then ever 6 months for 2 years
Biologic Effect of EGFR and VEGFR2 Inhibition
Effect of treatment on EGFR and VEGFR2 inhibition
Measured: Baseline and 3 and 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Aug 2011 (estimated)
- Study startJan 2012
- Primary completion1 Jan 2019
- Study completion1 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Lip and Oral Cavity Squamous Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by University of ChicagoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Chicago
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Tanguy Seiwert, M.D., Principal investigator, University of Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01414426
- Sponsor's protocol ID
- 11-0265
- Other IDs
- NCI-2011-01246
- Status last verified
- Jan 2021
- First submitted
- 9 Aug 2011
- Last updated
- 14 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Placebo- Controlled Pilot Study of ZD6474 as a Chemopreventive Agent for Premalignant Lesions of the Head and Neck
- ClinicalTrials.gov ID
- NCT01414426
- Acronym / sponsor ID
- 11-0265
- Conditions
- Lip and Oral Cavity Squamous Cell Carcinoma, Oral Cavity Verrucous Carcinoma, Precancerous Condition
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of ChicagoUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Jan 2012
- Primary completion
- 1 Jan 2019 (actual)
- Study completion
- 1 Jun 2019 (actual)
- First posted
- 11 Aug 2011 (estimated)
- Results
- Posted 14 Jan 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This randomized phase II trial studies how well vandetanib works in preventing head and neck cancer in patients with precancerous head and neck lesions. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of vandetanib may keep cancer from forming in patients with premalignant lesions
Detailed description
PRIMARY OBJECTIVE:
- Determine the effect of ZD6474 (vandetanib) compared to placebo on microvessel density (MVD) from baseline to 3 months in patients at risk for oral squamous cell carcinoma (OSCC) with preneoplastic lesions.
SECONDARY OBJECTIVES:
- Change in MVD over 6 months. II. Change in putative targets of ZD6474: tissues will be analyzed by immunohistochemistry (IHC) for phosphorylated epidermal growth factor receptor (pEGFR), EGFR, phosphorylated-vascular endothelial growth factor receptor 2 (pVEGFR2), VEGFR2.
III. Change in proliferative index as measured by Ki-67 IHC. IV. Safety, tolerability, and adherence to ZD6474 for 6 months in patients at risk for OSCC.
TERTIARY OBJECTIVES:
- Compare OSCC incidence in both study arms (ZD6474 and placebo).
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive vandetanib orally (PO) once daily (QD) for 6 months. Treatment continues in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive placebo PO QD for 6 months. Treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 9 and 12 months and then every 6 months for 2 years.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (chemoprevention) | Experimental | Drug: vandetanib, Other: immunohistochemistry staining method, Other: laboratory biomarker analysis, Procedure: biopsy, Other: pharmacological studyPatients receive vandetanib PO QD for 6 months. Treatment continues in the absence of disease progression or unacceptable toxicity. |
| Arm II (placebo) | Placebo comparator | Other: placebo, Other: immunohistochemistry staining method, Other: laboratory biomarker analysis, Procedure: biopsy, Other: pharmacological studyPatients receive placebo PO QD for 6 months. Treatment continues in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Histological/cytological confirmation of oral cavity dysplasia and one of three additional criteria:
- Prior history of OSCC
- Loss of heterozygosity (LOH) at 3p or 9p
- Expression by immunohistochemistry (IHC) of budding uninhibited by benzimidazoles 3 (BUB3)/sex determining region Y (SOX4)
- Provision of informed consent
Key exclusion criteria (25 listed)
- History of malignancy within the last 5 years other than squamous cell carcinoma of the head and neck (SCCHN) and superficial non-melanoma skin cancer; patients with a history of SCCHN must be free of active carcinoma
- Currently receiving treatment for any malignancy
- Serum bilirubin > 1.5x the upper limit of reference range (ULRR)
- Creatinine clearance =< 30 mL/minute (calculated by Cockcroft-Gault formula)
- Potassium, < 4.0 mmol/L despite supplementation; or above the Common Terminology Criteria for Adverse Events (CTCAE) grade 1 upper limit
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| vandetanibAlso: AZD6474, ZD6474Given PO | Drug | Arm I (chemoprevention) |
| placeboAlso: PLCBGiven PO | Other | Arm II (placebo) |
| immunohistochemistry staining methodAlso: immunohistochemistryCorrelative studies | Other | Arm I (chemoprevention), Arm II (placebo) |
| laboratory biomarker analysisCorrelative studies | Other | Arm I (chemoprevention), Arm II (placebo) |
| biopsyAlso: biopsiesCorrelative studies | Procedure or surgery | Arm I (chemoprevention), Arm II (placebo) |
| pharmacological studyAlso: pharmacological studiesCorrelative studies | Other | Arm I (chemoprevention), Arm II (placebo) |
Primary outcome
Comparison Between Treatment Groups of the Within-patient Change in MVD Score Following Treatment Initiation
Time frame: Baseline to 3 months
A Wilcoxon ranksum test may be used if the normality assumption is not satisfied. Alternatively, change in MVD may be transformed (e.g. log-transformation) to satisfy the normality assumption. Additional analyses will include linear regression models with treatment effect and other prognostic factors as covariates.
4 secondary outcomes
Number of Participants With Adverse Events
Time frame: Weekly during treatment, up to week 24
Number of Participants Who Adhered to Treatment
Time frame: Over 6 months
Development of Oral and Other Cancers
Time frame: At 6, 9, and 12 months and then ever 6 months for 2 years
Biologic Effect of EGFR and VEGFR2 Inhibition
Time frame: Baseline and 3 and 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tanguy Seiwert, M.D. principal investigator
University of Chicago
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing vandetanib, immunohistochemistry staining method and laboratory biomarker analysis in people with Lip and Oral Cavity Squamous Cell Carcinoma and Oral Cavity Verrucous Carcinoma, run by University of Chicago at 1 site 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 8 inclusion and 25 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 14 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. Some participants in this study may receive a placebo. 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 14 Jan 2021). 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?
Comparison Between Treatment Groups of the Within-patient Change in MVD Score Following Treatment Initiation (time frame: Baseline to 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 14 Jan 2021.