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

This study has been terminated.
(Due to a lack of funding)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Roswell Park Cancer Institute
ClinicalTrials.gov Identifier:
NCT01682031
First received: September 5, 2012
Last updated: August 8, 2014
Last verified: August 2014
  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
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:


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.


Enrollment: 18
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
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
Results First Received: June 26, 2014
Last Updated: August 8, 2014
Health Authority: United States: Institutional Review Board
United States: Federal Government

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Laryngeal Neoplasms
Carcinoma
Oropharyngeal Neoplasms
Nasopharyngeal Neoplasms
Paranasal Sinus Neoplasms
Mucositis
Xerostomia
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Laryngeal Diseases
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Otorhinolaryngologic Diseases
Pharyngeal Neoplasms
Pharyngeal Diseases
Stomatognathic Diseases
Nasopharyngeal Diseases
Nose Neoplasms
Nose Diseases
Paranasal Sinus Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Mouth Diseases

ClinicalTrials.gov processed this record on October 16, 2014