Selenomethionine in Reducing Mucositis in Patients With Locally Advanced Head and Neck Cancer Who Are Receiving Cisplatin and Radiation Therapy

Xerostomia Clinical Trial

Official title:

Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Phase II Trial of Selenomethionine as a Modulator of Efficacy and Toxicity of Chemoradiation in Locally-Advanced Squamous Cell Carcinoma of the Head and Neck

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01682031
• Other study ID #: I 107807
• Secondary ID: NCI-2009-01503
• Status: Terminated
• Phase: Phase 2
• First received: September 5, 2012
• Last updated: August 8, 2014
• Start date: June 2009
• Est. completion date: June 2012

Study information

• Verified date: August 2014
• Source: Roswell Park Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Federal Government
• Study type: Interventional

Clinical Trial Summary

This randomized phase II trial is studying how well selenomethionine (SLM) works in reducing mucositis in patients with locally advanced head and neck cancer who are receiving cisplatin and radiation therapy. SLM may help prevent or reduce mucositis, or mouth sores, in patients receiving chemotherapy and radiation therapy. It is not yet known whether SLM is more effective than a placebo in reducing mucositis

Description:

PRIMARY OBJECTIVES:

I. To assess whether SLM reduces the incidence of grade 3 or 4 mucositis in head and neck squamous cell carcinoma (HNSCC) patients treated with concurrent chemoradiation (CRT) over 7 weeks.

SECONDARY OBJECTIVES:

I. To assess the impact of SLM on tumor complete response rate, relapse-free survival, overall survival and quality of life.

II. To assess whether SLM reduces the incidence and severity of treatment-related toxicities including xerostomia, renal impairment and myelosuppression.

III. To assess whether SLM improves chemoradiation dose delivery. IV. To determine safety of SLM at this dose. V. In New Zealand (NZ) patients only, to assess the impact of SLM on plasma free cisplatin and plasma selenium pharmacokinetics (PK) and on pharmacodynamic (PD) markers of biological activity of selenium.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive placebo orally (PO) twice daily in week 1 and then once daily in weeks 2-11. Patients also receive cisplatin intravenously (IV) over 3 hours once in weeks 2, 5, and 8 and undergo radiotherapy 5 days a week in weeks 2-8.

ARM II: Patients receive selenomethionine PO twice daily in week 1 and then once daily in weeks 2-11. Patients also receive cisplatin and undergo radiotherapy as in arm I.

After completion of study treatment, patients are followed up periodically.

Other known NCT identifiers

• NCT00935038

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 18
• Est. completion date: June 2012
• Est. primary completion date: April 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Biopsy-proven locally-advanced HNSCC, including those with cancers of the oral cavity, oropharynx, hypopharynx, larynx, nasopharynx or paranasal sinuses

• Stage III, IVa or IVb disease

• No prior definitive surgery for present diagnosis

• Appropriate candidate for concurrent cisplatin and radiation as definitive treatment; patients who receive induction chemotherapy as part of a definitive treatment program that will include concurrent CRT are eligible for this study

• Hemoglobin >= 10 g/dL (100 g/l)

• Absolute neutrophil count >= 2,000 cells/mm^3 (2 x 10^9/l)

• Platelets >= 100,000 cells/mm^3 (100 x 10^9/l)

• Serum creatinine =< 1.5 mg/dL (133 umol/l) or calculated creatinine clearance >= 50 ml/min using the Cockcroft-Gault formula

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

• Able to give written informed consent

• Be willing and able to comply with study procedures

Exclusion Criteria:

• Non-regional metastatic disease (stage IVc)

• Previous malignancy within the last 5 years except for adequately treated basal or squamous cell carcinoma of the skin or cervical intra-epithelial neoplasia

• Prior chemotherapy or radiotherapy for HNSCC, or any prior radiotherapy that would compromise delivery of a radical dose to the HNSCC

• Known to be positive for hepatitis C or human immunodeficiency virus (HIV)

• Unable to tolerate oral medication (unless a feeding tube is in place)

• History of hypersensitivity to platinum drugs

• Symptomatic peripheral neuropathy >= National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) grade II

• Pregnant, lactating or unwilling to use adequate contraception

• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation

• Planned use of amifostine for prophylaxis against radiation-induced xerostomia

• Patients taking selenium supplements in excess of 100 ug/day

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Evidence of any other significant medical disorder or laboratory finding that in the opinion of the Investigator compromises the subject's safety during the study

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Chemotherapeutic Agent Toxicity
• Laryngeal Neoplasms
• Mucositis
• Nasopharyngeal Neoplasms
• Oropharyngeal Neoplasms
• Paranasal Sinus Neoplasms
• Radiation Toxicity
• Stage III Squamous Cell Carcinoma of the Hypopharynx
• Stage III Squamous Cell Carcinoma of the Larynx
• Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity
• Stage III Squamous Cell Carcinoma of the Nasopharynx
• Stage III Squamous Cell Carcinoma of the Oropharynx
• Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
• Stage IV Squamous Cell Carcinoma of the Hypopharynx
• Stage IV Squamous Cell Carcinoma of the Larynx
• Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity
• Stage IV Squamous Cell Carcinoma of the Nasopharynx
• Stage IV Squamous Cell Carcinoma of the Oropharynx
• Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
• Xerostomia

Intervention

Dietary Supplement:
• selenomethionine
Given PO

Other:
• placebo
Given PO

Drug:
• cisplatin
Given IV

Radiation:
• radiation therapy
Undergo radiotherapy

Procedure:
• quality-of-life assessment
Ancillary studies

Locations

Country	Name	City	State
New Zealand	Waikato Hospital	Hamilton
United States	Roswell Park Cancer Institute	Buffalo	New York

Sponsors (2)

Lead Sponsor	Collaborator
Roswell Park Cancer Institute	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of >= Grade 3 Mucositis	Will be compared as difference in proportions with 95% confidence intervals.	Up to 5 years	Yes
Secondary	Tumor Complete Response Rate	Will be compared as difference in proportions with 95% confidence intervals. Disease will be measured according to the Response Evaluation Criteria in Solid Tumors (RECIST).	Up to 5 years post-treatment	No
Secondary	Relapse-free Survival (RFS)	Assessed by Kaplan-Meier RFS curves and the proportion with an event at 1 year for RFS will be compared simultaneously to obtain more global sensitivity to differences in time-to-event.	At 1 year	No
Secondary	Overall Survival	Estimated using the Kaplan-Meier method. Log-rank tests will be used for the comparison of survival distributions among study groups. Continuous endpoints will be summarized using means, standard deviations and percentiles.	Up to 5 years post-treatment	No
Secondary	Quality of Life		Up to 1 year post-treatment	No
Secondary	Incidence of Grade 3 or 4 Treatment-related Toxicities, Including Xerostomia	Will be compared as difference in proportions with 95% confidence intervals.	Up to 5 years post-treatment	Yes
Secondary	CRT Dose Delivery	This characteristic will be included in Cox models.	Up to 8 weeks	No
Secondary	Plasma Cisplatin and Selenium PK and PD Markers (NZ Only)	Descriptive statistics will be used to describe the mean plasma cisplatin and selenium at each time point. Repeated measures analysis of variance will be used to evaluate the changes in plasma cisplatin and selenium over time. Analysis of pharmacodynamic markers will be conducted using statistical methods appropriate for within-patient sequential analyses, such as repeated measures analysis of variance.	Up to 3 months post-treatment	No