Clinical trial NCT03101514
Conditions: Head and Neck Cancer Radiotherapy
Keywords: head and neck tumor radiotherapy mucositis toxicity Kanglaite injection
Sponsor: First Affiliated Hospital of Harbin Medical University
Start date: 2017-01-01; Completion date: 2021-02-01
Enrollment: 53 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
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:
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%.

Arms: arm 1: Kanglaite 200ml is injected once a day from Monday to Friday during radiotherapy.
Interventions: intervention 1: Kanglaite intervention 2: chemotherapy
Intervention descriptions: intervention 1: Kanglaite injection 200ml is injected intravenous from the first day to the last day of radiotherapy. intervention 2: Cisplatin 80-100mg/m2 was used every 3 weeks during radiotherapy.

Protocol documents:
Prot_SAP_000.pdf: 
 
 
 
 
 
Kanglaite Reduce the Toxicity of Radiotherapy 
of Head and Neck Cancer Phase II Study 
 
NCT03101514 
January 6, 2017 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Study Protocol and Statistical Analysis Plan 
 
Patients 
Patients aged 18–80 years with pathologically confirmed head and neck cancer 
receiving radical or postoperative radiotherapy and Karnofsky score greater than 80 
points were eligible for recruitment. Patients who received radiotherapy only, 
radiotherapy concurrent with single-drug platinum chemotherapy, or induction 
chemotherapy with fewer than three cycles were eligible. Patients with a history of 
head and neck radiotherapy, distant metastases, and targeted drug or non-platinum 
drug chemotherapy during radiotherapy were excluded.  
 
Treatments 
All patients received 20 g Kanglaite (200 mL) daily, administered as an 
intravenous injection for 5 days a week, concurrently with radiotherapy. Kanglaite 
injection was used before or after radiotherapy, no time interval requirement between 
Kanglaite and radiotherapy. The dosage of radiotherapy was adjusted as follows: 70 
Gy for gross tumors and positive lymph nodes, 66 Gy for tumor bed (operation bed), 
60 Gy for high-risk lymph node drainage area, and 50 Gy for low-risk lymph node 
drainage area. Single fraction dose was 1.82–2.12 Gy for 5 days a week, once a day. 
Intensity-modulated radiation therapy was used and the radiotherapy planning system 
used was Eclipse 7.0. Recombinant human granulocyte colony-stimulating factor and 
antibiotics were not allowed as prophylactic treatments. After the final patient 
completed radiotherapy and observation data was recorded, the trial stopped.  
 
Study end-points  
Primary end-point was the incidence of radiation-induced mucositis. Secondary 
end-points were as follows: (i) blood toxicity, liver and kidney functions, and other 
toxic events; (ii) nutritional status, overall QOL, and QOL specifically related to head 
and neck. 
All the end-points could be observed in the course of radiotherapy; therefore, 
long-term follow-up data may be reported in the future. After radiotherapy, patients 


were evaluated for recurrence, metastases, and death every 3 months in the first 3 
years, and every 6 months thereafter until death. 
 
Evaluation of data  
Acute toxicity indicators 
Mucositis and the associated symptoms (manifested as pain, dysphagia, or dry 
mouth), blood cell count, liver and kidney functions, and other toxic events were 
assessed at baseline (before radiotherapy), every week during radiotherapy, and post 
radiotherapy. All adverse events were graded according to NCI Common 
Terminology Criteria for Adverse Events v4.0 (NCI-CTCAE4.0).  
Mucositis in patients with head and neck cancer receiving radiotherapy usually 
occurs in the oral cavity, oropharynx, hypopharynx, and larynx. In NCI CTCAE4.0, 
grade 1 oral mucositis, pharyngeal mucositis, and laryngeal mucositis are defined as 
those causing mild discomfort in normal oral intake, requiring no intervention. Grade 
2 mucositis is defined as that causing moderate pain, not interfering with oral intake, 
but altering oral intake. Grade 3 mucositis is defined as that causing severe pain, with 
severely altered eating/swallowing, requiring medical intervention. Grade 4 mucositis 
is defined as that with life-threatening consequences, requiring urgent intervention. 
Grade 5 mucositis is defined as that causing death. 
Blood cell count, liver and kidney functions were assessed at baseline (before 
radiotherapy)—via blood test—every week during radiotherapy, and post 
radiotherapy. The lowest scores during radiotherapy were recorded and considered as 
data. 
Nutritional status 
Nutritional status was scored using the Patient-Generated Subjective Global 
Assessment (PG-SGA). The scores 0–1 is well-nourished or anabolic, scores 2–8 is 
suspected or moderate under-nutrition, score ≥9 is severely undernourished. The 
PG-SGA scores were recorded at baseline (before radiotherapy), every week during 
radiotherapy, and post radiotherapy. The highest PG-SGA scores recorded every 
week during the course of radiotherapy were used as the data obtained during 


radiotherapy. 
Therapeutic nutritional supports were provided based on the grade of dysphagia. 
Nutritional supports were divided into oro–enteral nutrition preparation, tube feeding, 
total parenteral nutrition, and separated nutrition infusion. Total parenteral nutrition 
was defined as a combination of amino acids, carbohydrates, and fats administered 
intravenously. Separate nutrition infusion was defined as intravenous administration 
of any one amino acid, carbohydrate, and fat. Nutritional treatment was not 
considered for those receiving nutritional treatment for less than 3 days or <10 kcal/kg 
per day.  
Quality of life score 
European Organization for Research and Treatment of Cancer (EORTC) 
QLQ-C30 questionnaire was used to evaluate the overall QOL. European 
Organization for Research and Treatment of Cancer QLQ-Head and Neck 35 
(EORTC QLQ-H&N35) questionnaire was used to evaluate QOL specific for head 
and neck. Quality of life for each patient was assessed at baseline (before 
radiotherapy), every week during radiotherapy, and post radiotherapy using the 
EORTC QLQ-C30 and EORTC QLQ-H&N35 questionnaires. The QLQ-C30 and 
QLQ-H&N35 questionnaires were distributed to patients weekly during radiotherapy, 
and the lowest scores were recorded as data during radiotherapy. Using the EORTC 
Group scoring guidelines, each item of the QLQ-C30 and QLQ-H&N35 
questionnaires was scored from 0 to 100. Higher scores for functions in QLQ-C30 
implied a better quality of life; higher scores for the symptoms in QLQ-C30 and all 
items in QLQ-H&N35 indicated worsening quality of life.  
 
Statistical analysis  
Descriptive statistics were used to summarize patient baseline characteristics. 
Normally distributed data are reported as mean and standard deviation. Qualitative 
data are presented as number of observations and percentages. All statistical analyses 
were conducted using SPSS Statistics v. 18 (IBM Corporation, NY, USA). A 
two-tailed p <0.05 was considered statistically significant.