Botanical Therapy in Treating Mucositis in Patients With Head and Neck Cancer Who Have Undergone Chemoradiation Therapy

Study Overview
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Brief Summary
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The purpose of this study is to find out what effects (good and bad) SAMITAL (Vaccinium myrtillus extract/Macleaya cordata alkaloids/Echinacea angustifolia extract granules) has on the management of mucositis (inflammation and ulceration that occurs in the mouth) brought on by chemotherapy and radiation therapy for squamous cell carcinoma of the head and neck

Detailed Description
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PRIMARY OBJECTIVES: I. To assess the tolerability of SAMITAL granules for suspension. II. To assess the efficacy of SAMITAL granules for suspension in reducing the incidence of severe mucositis (World Health Organization [WHO] mucositis scale score of 3 or 4) induced by concurrent chemoradiation for head and neck cancer (HNC). SECONDARY OBJECTIVES: I. To assess the effect of SAMITAL granules for suspension on the severity and duration of mucositis (WHO mucositis scale and patient self-assessment with the Oral Mucositis Daily Questionnaire [OMDQ]). II. To assess the effect of SAMITAL granules for suspension on validated patient reported quality of life measures (European Organization for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire [QLQ]-C30 and EORTC QLQ Head and Neck Cancer Specific Module). III. To assess the rate of any grade 3 - grade 4 infections. IV. To assess the cumulative dose of opioids needed. V. To assess weight loss and need for tube feeding. VI. To assess treatment breaks and/or chemotherapy dose reduction. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Beginning as soon as symptoms arise during chemoradiotherapy, patients receive Vaccinium myrtillus extract/Macleaya cordata alkaloids/Echinacea angustifolia extract granules orally (PO) four times daily (QID). Patients may continue to receive Vaccinium myrtillus extract/Macleaya cordata alkaloids/Echinacea angustifolia extract granules for up to 4 weeks after completion of radiation therapy for a maximum of 11 weeks. ARM II: Beginning as soon as symptoms arise during chemoradiotherapy, patients receive placebo PO QID. Patients may continue to receive placebo for up to 4 weeks after completion of radiation therapy for a maximum of 11 weeks. After completion of study treatment, patients are followed up for 3 months.

Official Title
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A Phase 2 Placebo Controlled Randomized Study of the Effect of SAMITAL on Severity and Duration of Mucositis Induced by Chemoradiation for Head and Neck Cancer (HNC)

Conditions
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Mucositis, Recurrent Squamous Cell Carcinoma of the Hypopharynx, Recurrent Squamous Cell Carcinoma of the Larynx, Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity, Recurrent Squamous Cell Carcinoma of the Nasopharynx, Recurrent Squamous Cell Carcinoma of the Oropharynx, Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Recurrent Verrucous Carcinoma of the Larynx, Recurrent Verrucous Carcinoma of the Oral Cavity, 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 III Verrucous Carcinoma of the Larynx, Stage III Verrucous Carcinoma of the Oral Cavity, Stage IV Squamous Cell Carcinoma of the Hypopharynx, Stage IV Squamous Cell Carcinoma of the Nasopharynx, Stage IVA Squamous Cell Carcinoma of the Larynx, Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IVA Squamous Cell Carcinoma of the Oropharynx, Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage IVA Verrucous Carcinoma of the Larynx, Stage IVA Verrucous Carcinoma of the Oral Cavity, Stage IVB Squamous Cell Carcinoma of the Larynx, Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IVB Squamous Cell Carcinoma of the Oropharynx, Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage IVB Verrucous Carcinoma of the Larynx, Stage IVB Verrucous Carcinoma of the Oral Cavity, Tongue Cancer

Intervention / Treatment
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* Other: placebo
* Procedure: quality-of-life assessment
* Other: questionnaire administration
* Drug: Vaccinium myrtillus/Macleaya cordata/Echinacea angustifolia extract granules


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2 Patients with no distant metastatic disease Have histologically proven diagnosis of squamous cell carcinoma (stage III - IV) of the paranasal sinuses, nasopharynx, larynx, hypopharynx, oral cavity and/or oropharynx; treated with definitive concurrent chemoradiotherapy; OR histologically proven diagnosis of squamous cell carcinoma of the paranasal sinuses, nasopharynx, larynx, hypopharynx, or oropharynx with finding of need for concurrent chemoradiotherapy (extracapsular extension, positive surgical margin, more than one lymph node positive, stage III - IV disease, perineural invasion, vascular tumor embolus); other rare histologies which are treated as per the guidelines of this protocol may be allowed with approval of the medical monitor Concurrent monochemotherapy with cisplatin Radiation therapy to 70 Gray (Gy) to gross tumor in 2 Gy per fraction over 7 weeks using intensity modulated radiation therapy (IMRT) techniques for patients with intact tumors, and 60 Gy - 66 Gy in 2 Gy per fraction using IMRT for post-operative patients Induction chemotherapy (with up to 3 cycles of docetaxel and cisplatin based regimens) is allowed Ability to swallow and retain oral medication Leukocytes >= 3,000/uL Absolute neutrophil count >= 1,500/uL Platelets >= 100,000/uL Total bilirubin within normal institutional limits Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit normal (ULN) Calculated creatinine clearance >= 60 mL/min (Cockcroft-Gault equation) Patients of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately Patient or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure Exclusion Criteria: Contraindication to full course chemoradiotherapy ECOG performance status >= 3 Presence of distant metastatic disease Surgery with significant defect or flap in the oral cavity Poor dentition, ill-fitting dental appliances, obturators or any kind of resection prosthesis (can be enrolled if this can be corrected by a dentist prior to start of radiation therapy) Presence of other medical conditions causing mucositis (e.g., rheumatologic, severe gastroesophageal reflux, etc. at the discretion of the physician) Previous radiotherapy on head and neck district involving mucosa of oral cavity and/or oropharynx Use of chronic immunosuppressive drugs Brachytherapy or interstitial implantation treatment Other medical conditions that could make the patient not able to comply with the treatment Requirement of chronic steroid therapy (except when given for laryngeal edema) Pregnant or nursing female patients Unwilling or unable to follow protocol requirements Any condition which in the Investigator's opinion deems the patient an unsuitable candidate to receive study drug Received an investigational agent within 30 days prior to enrollment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (SAMITAL)<br>Beginning as soon as symptoms arise during chemoradiotherapy, patients receive Vaccinium myrtillus extract/Macleaya cordata alkaloids/Echinacea angustifolia extract granules PO QID. Patients may continue to receive Vaccinium myrtillus extract/Macleaya cordata alkaloids/Echinacea angustifolia extract granules for up to 4 weeks after completion of radiation therapy for a maximum of 11 weeks. | Procedure: quality-of-life assessment<br>* Ancillary studies<br>* Other names: quality of life assessment;Other: questionnaire administration<br>* Ancillary studies<br>Drug: Vaccinium myrtillus/Macleaya cordata/Echinacea angustifolia extract granules<br>* Given PO<br>* Other names: V. myrtillus/M. cordata/E. angustfolia granules;|
| Placebo Comparator: Arm II (placebo)<br>Beginning as soon as symptoms arise during chemoradiotherapy, patients receive placebo PO QID. Patients may continue to receive placebo for up to 4 weeks after completion of radiation therapy for a maximum of 11 weeks. | Other: placebo<br>* Given PO<br>* Other names: PLCB;Procedure: quality-of-life assessment<br>* Ancillary studies<br>* Other names: quality of life assessment;Other: questionnaire administration<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with severe mucositis (WHO score 3 or 4) | The 2 treatment groups will be compared using the Mantel-Haenszel test, stratified by disease site and type of therapy, using a two-sided test at the alpha= 0.10 level of significance. Since emphasis is placed on the accurate estimation of treatment effect for use in the planning of a future confirmatory trial, corresponding estimates of effect size will also be computed along with 90% confidence intervals. | Up to 3 months after completion of study treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severity and duration of mucositis as assessed by dichotomized WHO Mucositis Global Severity Score (0-2 vs 3-4) and/or OMDQ scores | The 2 treatment groups will be compared. The Mantel-Haenszel test, stratified by disease site and type of therapy, will be used for these comparisons. | Up to 3 months after completion of study treatment | 
| Quality of life as assessed by EORTC QLQ-C30 questionnaire (with 1 being not at all and 4 being very much) | The 2 treatment groups will be compared. Will be analyzed using Mann-Whitney U tests. All secondary analyses will be carried out using two-sided tests at the 10% level of significance. | Up to 3 months after completion of study treatment | 
| Quality of Life as assessed by EORTC QLQ Head and Neck Cancer-Specific Module function and symptom sub-scores between groups (with 1 being not at all and 4 being very much) | The 2 treatment groups will be compared. Will be analyzed using Mann-Whitney U tests. All secondary analyses will be carried out using two-sided tests at the 10% level of significance. | Up to 3 months after completion of study treatment |