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

Primary Purpose

Chemotherapeutic Agent Toxicity, Mucositis, Radiation Toxicity

Status

Terminated

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

selenomethionine

placebo

cisplatin

radiation therapy

quality-of-life assessment

About this trial

This is an interventional supportive care trial for Chemotherapeutic Agent Toxicity

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Roswell Park Cancer Institute
Waikato Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Arm I (placebo, cisplatin, and radiotherapy)

Arm II (selenomethionine, cisplatin, and radiotherapy)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Incidence of >= Grade 3 Mucositis

Will be compared as difference in proportions with 95% confidence intervals.

Secondary Outcome Measures

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).

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.

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.

Quality of Life

Incidence of Grade 3 or 4 Treatment-related Toxicities, Including Xerostomia

Will be compared as difference in proportions with 95% confidence intervals.

CRT Dose Delivery

This characteristic will be included in Cox models.

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.

Full Information

NCT ID

NCT01682031

First Posted

September 5, 2012

Last Updated

August 8, 2014

Sponsor

Roswell Park Cancer Institute

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT01682031

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2014

Overall Recruitment Status

Terminated

Why Stopped

Due to a lack of funding

Study Start Date

June 2009 (undefined)

Primary Completion Date

April 2012 (Actual)

Study Completion Date

June 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Roswell Park Cancer Institute

Collaborators

National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Supportive Care

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

Double

Allocation

Randomized

Enrollment

18 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm I (placebo, cisplatin, and radiotherapy)

Arm Type

Placebo Comparator

Arm Description

Arm Title

Arm II (selenomethionine, cisplatin, and radiotherapy)

Arm Type

Experimental

Arm Description

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.

Intervention Type

Dietary Supplement

Intervention Name(s)

selenomethionine

Intervention Description

Given PO

Intervention Type

Other

Intervention Name(s)

placebo

Other Intervention Name(s)

PLCB

Intervention Description

Given PO

Intervention Type

Drug

Intervention Name(s)

cisplatin

Other Intervention Name(s)

CACP, CDDP, CPDD, DDP

Intervention Description

Given IV

Intervention Type

Radiation

Intervention Name(s)

radiation therapy

Other Intervention Name(s)

irradiation, radiotherapy, therapy, radiation

Intervention Description

Undergo radiotherapy

Intervention Type

Procedure

Intervention Name(s)

quality-of-life assessment

Other Intervention Name(s)

quality of life assessment

Intervention Description

Ancillary studies

Primary Outcome Measure Information:

Title

Incidence of >= Grade 3 Mucositis

Description

Will be compared as difference in proportions with 95% confidence intervals.

Time Frame

Up to 5 years

Secondary Outcome Measure Information:

Title

Tumor Complete Response Rate

Description

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

Title

Relapse-free Survival (RFS)

Description

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

Title

Overall Survival

Description

Time Frame

Up to 5 years post-treatment

Title

Quality of Life

Time Frame

Up to 1 year post-treatment

Title

Incidence of Grade 3 or 4 Treatment-related Toxicities, Including Xerostomia

Description

Will be compared as difference in proportions with 95% confidence intervals.

Time Frame

Up to 5 years post-treatment

Title

CRT Dose Delivery

Description

This characteristic will be included in Cox models.

Time Frame

Up to 8 weeks

Title

Plasma Cisplatin and Selenium PK and PD Markers (NZ Only)

Description

Time Frame

Up to 3 months post-treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Anurag Singh

Organizational Affiliation

Roswell Park Cancer Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

Roswell Park Cancer Institute

City

Buffalo

State/Province

New York

ZIP/Postal Code

14263

Country

United States

Facility Name

Waikato Hospital

City

Hamilton

ZIP/Postal Code

3204

Country

New Zealand

12. IPD Sharing Statement

Learn more about this trial

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

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