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
Conditions
Brief 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
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.
Interventions
Given PO
Given PO
Given IV
Undergo radiotherapy
Ancillary studies
Sponsors
Study design
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of >= Grade 3 Mucositis | Up to 5 years | Will be compared as difference in proportions with 95% confidence intervals. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relapse-free Survival (RFS) | At 1 year | 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 | Up to 5 years post-treatment | 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 | Up to 1 year post-treatment | — |
| Tumor Complete Response Rate | Up to 5 years post-treatment | 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). |
| CRT Dose Delivery | Up to 8 weeks | This characteristic will be included in Cox models. |
| Plasma Cisplatin and Selenium PK and PD Markers (NZ Only) | Up to 3 months post-treatment | 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. |
| Incidence of Grade 3 or 4 Treatment-related Toxicities, Including Xerostomia | Up to 5 years post-treatment | Will be compared as difference in proportions with 95% confidence intervals. |
Countries
New Zealand, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
placebo: Given PO
cisplatin: Given IV
radiation therapy: Undergo radiotherapy
quality-of-life assessment: Ancillary studies | 8 |
| 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.
selenomethionine: Given PO
cisplatin: Given IV
radiation therapy: Undergo radiotherapy
quality-of-life assessment: Ancillary studies | 10 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
| Overall Study | MRI results indicate increased nodul | 0 | 1 |
| Overall Study | Patient could not swallow tablets | 1 | 0 |
| Overall Study | Patient stopped selenium on his own | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Arm I (Placebo, Cisplatin, and Radiotherapy) | Arm II (Selenomethionine, Cisplatin, and Radiotherapy) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 9 Participants | 16 Participants |
| Age, Continuous | 56.6 years STANDARD_DEVIATION 6.6 | 57.4 years STANDARD_DEVIATION 8.2 | 57.1 years STANDARD_DEVIATION 7.3 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 8 Participants | 10 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 8 | 10 / 10 |
| serious Total, serious adverse events | 4 / 8 | 2 / 10 |
Outcome results
Incidence of >= Grade 3 Mucositis
Will be compared as difference in proportions with 95% confidence intervals.
Time frame: Up to 5 years
Population: Due to the study's early termination and inadequate number of patients, no patients were analyzed.
CRT Dose Delivery
This characteristic will be included in Cox models.
Time frame: Up to 8 weeks
Population: Due to the study's early termination and inadequate number of patients, no patients were analyzed.
Incidence of Grade 3 or 4 Treatment-related Toxicities, Including Xerostomia
Will be compared as difference in proportions with 95% confidence intervals.
Time frame: Up to 5 years post-treatment
Population: All treated and eligible patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I (Placebo, Cisplatin, and Radiotherapy) | Incidence of Grade 3 or 4 Treatment-related Toxicities, Including Xerostomia | 1 number of xerostomia events |
| Arm II (Selenomethionine, Cisplatin, and Radiotherapy) | Incidence of Grade 3 or 4 Treatment-related Toxicities, Including Xerostomia | 0 number of xerostomia events |
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.
Time frame: Up to 5 years post-treatment
Population: Due to the study's early termination and inadequate number of patients, no patients were analyzed.
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.
Time frame: Up to 3 months post-treatment
Population: Due to the study's early termination and inadequate number of patients, no patients were analyzed.
Quality of Life
Time frame: Up to 1 year post-treatment
Population: Due to the study's early termination and inadequate number of patients, no patients were analyzed.
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.
Time frame: At 1 year
Population: Due to the study's early termination and inadequate number of patients, no patients were analyzed.
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).
Time frame: Up to 5 years post-treatment
Population: Due to the study's early termination and inadequate number of patients, no patients were analyzed.