Kanglaite Reduce the Toxicity of Radiotherapy of Head and Neck Cancer Phase II Study

Study Overview
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Brief Summary
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About 89%-100% patients with head and neck malignant tumors have radiation mucositis during their radiotherapy. Until now, there is no effective method to prevent mucositis. Steroid hormone, pain-relief, anti-inflammatory and other symptom-relief treatments usually are used after the emergence of mucositis. Coixenol triglyceride is an ester extract of Coix Seed. Its trade name is Kanglaite Injection, which has been approved in China and Russia. Kanglaite has anti-tumor effect and reduce treatment toxicity of tumor. Kanglaite could also improve the quality of life of patients and mitigate the condition of the cachexia. In china, two studies evaluating treatment of Kanglaite to nasopharyngeal cancer, found that Kanglaite can reduce radiotherapy mucositis. So far, Kanglaite on the prevention and treatment of radiation mucositis of the head and neck malignant tumor is still lack of strong clinical trial evidence. This is a phase II, single center, one arm study with subject to evaluate the acute radiation mucositis, nutritional status, and quality of life on the course of radiotherapy of head and neck cancer.

Detailed Description
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3-4 grade radiation mucositis account for 34%-56% in all head and neck patients treated by radiotherapy and >50% in patients treated by radiotherapy concurrent with chemotherapy. 3-4 grade radiation mucositis have obvious symptoms, presenting with fusion ulcers, ulcers bleeding or obvious pain need analgesic drugs. At this time, the patients can not eat or can only intake fluid diet, which led to weight loss, malnutrition, quality of life declined and a series of problems. Kanglaite has anti-tumor effect and reduce treatment toxicity of tumor. Kanglaite can reduce radiotherapy mucositis of nasopharyngeal cancer had been found initially in Chinese. Kanglaite on the prevention and treatment of radiation mucositis of the head and neck malignant tumor is still lack of strong clinical trial evidence. This is a phase II, single center, one arm study with subject to evaluation the acute radiation mucositis, nutritional status, and quality of life on the course of radiotherapy of head and neck malignant tumors. Kanglaite 200ml is injected intravenous from the first day to the last day of radiotherapy. Chemotherapy with cisplatin or nedaplatin (both 80-100mg/m2, 21 day per cycle, 1-3 cycles) is used or not concurrent with radiotherapy. There is no order of Kanglaite injection and radiotherapy. Granulocyte colony stimulating factor and antibiotics have no prophylactic use, but can be used after the decline of white blood cells. Mucositis, nutritional status, and quality of life are evaluated before radiotherapy, every week of radiotherapy, 4 weeks after radiotherapy. Mucositis is verified by physical examination. Nutritional status is evaluated by patient-generated subjective global assessment (PG-SGA) scale. Quality of life is evaluated by EORTC QLQ-C30 and QLQ-H&N35 questionnaire. This is a one arm study, sample size calculation based on the incidence of 3-4 degree mucositis. The incidence of 3-4 degree mucositis is about >50% according to literatures of head and neck squamous cell carcinoma intensity modulated radiation therapy concurrent with chemotherapy. So we assume that Kanglaite can reduce 3-4 degree mucositis from 50% to 30%. The sample size required 44 cases according to the superiority test, bilateral Class I error α = 0.05, class II error β = 0.2. Total 49 cases are need, assuming the off rate of 10%.

Official Title
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Kanglaite Reduce the Toxicity of Radiotherapy of Head and Neck Cancer Phase II Study

Conditions
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Head and Neck Cancer, Radiotherapy

Intervention / Treatment
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* Drug: Kanglaite
* Drug: chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-80 years old, expected survival period ≥ 12 months Karnofsky score ≥80 points Pathological confirmed head and neck malignant tumors (oral, oropharynx, hypopharynx, throat, nasopharynx, nasal paranasal sinus or other), radical radiotherapy (± chemotherapy) or postoperative radiotherapy (± chemotherapy), radiotherapy dose 60 -70Gy with or without induction chemotherapy (induced chemotherapy ≤ 3 cycles); Meet the following laboratory diagnostic indicators: Hemoglobin ≥120g / L, white blood cells 4.0-10.0 × 109 / L, neutrophils 2.0-7.5 × 109 / L, platelets 100-300 × 109 / L; creatinine ≤ normal upper limit (UNL); ALT and AST ≤ 2.5 × UNL, alkaline phosphatase (ALP) ≤ 5 × UNL, total bilirubin (Tbil) ≤ UNL Sign informed consent. Exclusion Criteria: Distant metastases Allergy to Kanglaite Head and neck had previously received radiation therapy Pregnancy or lactation patients Targeted drug therapy during radiotherapy Radio-chemotherapy uses cytotoxic drugs other than platinum Currently active infections, or combined with rheumatic immune diseases, long-term chronic infection, acute infection, inflammatory state; hematopoietic dysfunction of the blood system diseases; severe cardiopulmonary disease Mental history, can not cooperate with the treatment Researchers believe unsuitable to participate in this trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Prevention
Intervention Model: Single Group Assignment
Interventional Model Description: Kanglaite injection + Radiotherapy ± Chemotherapy
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Kanglaite group<br>Kanglaite 200ml is injected once a day from Monday to Friday during radiotherapy. | Drug: Kanglaite<br>* Kanglaite injection 200ml is injected intravenous from the first day to the last day of radiotherapy.<br>* Other names: Kanglaite injection;Drug: chemotherapy<br>* Cisplatin 80-100mg/m2 was used every 3 weeks during radiotherapy.<br>* Other names: Concurrent chemotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the Incidence Rate of Severe Radiation Mucositis | The grade of radiation mucositis was assessed by CTCAE v4. The highest grade be recorded. The grade 1 was the best and grade 4 was the worst. | From date of randomization until the end radiotherapy, up to 3 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the Incidence Rate of Non-Hematologic Toxicity Side Events | The non-hematologic toxicity side events were assessed by CTCAE v4. The highest grade be recorded. The grade 1 was the best and grade 4 was the worst. | From date of randomization until the end radiotherapy, up to 3 months. | 
| the Incidence Rate of Hematologic Toxicity Side Events | The grade of hematologic toxicity side events were assessed by CTCAE v4. The highest grade be recorded. The grade 1 was the best and grade 4 was the worst. | From date of randomization until the end radiotherapy, up to 3 months. | 
| the Nutritional Status | The nutritional status was assessed by PG-SGA questionnaire.PG-SGA scores were recorded weekly during radiotherapy. A score of 0-1 indicated good nourishment, 2-8 suspected or moderate malnutrition, ≥ 9 risk of severe malnutrition. | From date of randomization until the end radiotherapy, up to 3 months. | 
| the Overall Quality of Life (QOL) | The overall quality of life was assessed by EORTC QLQ-C30 questionnaire. QLQ-C30 scores were valued weekly during radiotherapy and post radiotherapy.The worst score of patients was recorded. The QLQ-C30 was scored from 0 to 100. Higher scores for function indicated a better QOL whereas the symptoms indicated a worsening QOL. | From date of randomization until the end radiotherapy, up to 3 months. | 
| Quality of Life Specific to Head and Neck Cancers | Quality of life specific to head and neck cancers was assessed by EORTC QLQ-H&N35 questionnaire. QLQ-H&N35 scores were valued weekly during radiotherapy and post radiotherapy. The highest score of patients was recorded. The QLQ-H&N35 was scored from 0 to 100. Higher scores indicated a worsening QOL. | From date of randomization until the end radiotherapy, up to 3 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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toxicity, Kanglaite injection, head and neck, tumor, radiotherapy, mucositis