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

Purpose

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

Condition	Intervention	Phase
Chemotherapeutic Agent Toxicity Mucositis 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	Dietary Supplement: selenomethionine Other: placebo Drug: cisplatin Radiation: radiation therapy Procedure: quality-of-life assessment	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Supportive Care
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Dry Mouth Head and Neck Cancer

Drug Information available for: Selenomethionine Cisplatin

U.S. FDA Resources

Further study details as provided by Roswell Park Cancer Institute:

Primary Outcome Measures:

Incidence of >= grade 3 mucositis [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
Will be compared as difference in proportions with 95% confidence intervals.

Secondary Outcome Measures:

Tumor complete response rate [ Time Frame: Up to 5 years post-treatment ] [ Designated as safety issue: No ]
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).
Relapse-free survival (RFS) [ Time Frame: At 1 year ] [ Designated as safety issue: No ]
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.
Overall survival [ Time Frame: Up to 5 years post-treatment ] [ Designated as safety issue: No ]
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.
Quality of life [ Time Frame: Up to 1 year post-treatment ] [ Designated as safety issue: No ]
Incidence of grade 3 or 4 treatment-related toxicities, including xerostomia [ Time Frame: Up to 5 years post-treatment ] [ Designated as safety issue: Yes ]
Will be compared as difference in proportions with 95% confidence intervals.
CRT dose delivery [ Time Frame: Up to 8 weeks ] [ Designated as safety issue: No ]
This characteristic will be included in Cox models.
Plasma cisplatin and selenium PK and PD markers (NZ only) [ Time Frame: Up to 3 months post-treatment ] [ Designated as safety issue: No ]
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.

Estimated Enrollment:	80
Study Start Date:	June 2009
Study Completion Date:	June 2012
Primary Completion Date:	April 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo Comparator: Arm I (placebo, cisplatin, and radiotherapy) Patients receive placebo PO twice daily in week 1 and then once daily in weeks 2-11. Patients also receive cisplatin IV over 3 hours once in weeks 2, 5, and 8 and undergo radiotherapy 5 days a week in weeks 2-8.	Other: placebo Given PO Other Name: PLCB Drug: cisplatin Given IV Other Names: CACP CDDP CPDD DDP Radiation: radiation therapy Undergo radiotherapy Other Names: irradiation radiotherapy therapy, radiation Procedure: quality-of-life assessment Ancillary studies Other Name: quality of life assessment
Experimental: Arm II (selenomethionine, cisplatin, and radiotherapy) 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.	Dietary Supplement: selenomethionine Given PO Drug: cisplatin Given IV Other Names: CACP CDDP CPDD DDP Radiation: radiation therapy Undergo radiotherapy Other Names: irradiation radiotherapy therapy, radiation Procedure: quality-of-life assessment Ancillary studies Other Name: quality of life assessment

Detailed 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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01682031

Locations

United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
New Zealand
Waikato Hospital
Hamilton, New Zealand, 3204

Sponsors and Collaborators

Roswell Park Cancer Institute

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Anurag Singh

Roswell Park Cancer Institute

More Information

No publications provided

Responsible Party:	Roswell Park Cancer Institute
ClinicalTrials.gov Identifier:	NCT01682031 History of Changes
Obsolete Identifiers:	NCT00935038
Other Study ID Numbers:	I 107807, NCI-2009-01503
Study First Received:	September 5, 2012
Last Updated:	April 23, 2013
Health Authority:	United States: Institutional Review Board United States: Federal Government

Additional relevant MeSH terms:

Paranasal Sinus Neoplasms
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Laryngeal Diseases
Xerostomia
Hypopharyngeal Neoplasms
Laryngeal Neoplasms
Radiation Injuries
Mucositis
Oropharyngeal Neoplasms
Nasopharyngeal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms

Neoplasms, Squamous Cell
Neoplasms by Site
Respiratory Tract Diseases
Otorhinolaryngologic Diseases
Salivary Gland Diseases
Mouth Diseases
Stomatognathic Diseases
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Pharyngeal Diseases
Respiratory Tract Neoplasms
Wounds and Injuries
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on May 16, 2013