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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03101514

Enrollment

Registered

2017-04-05

Start date

2017-01-01

Completion date

2021-02-01

Last updated

2021-06-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Head and Neck Cancer, Radiotherapy

Keywords

head and neck, tumor, radiotherapy, mucositis, toxicity, Kanglaite injection

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%.

Interventions

DRUGKanglaite

Kanglaite injection 200ml is injected intravenous from the first day to the last day of radiotherapy.

DRUGchemotherapy

Cisplatin 80-100mg/m2 was used every 3 weeks during radiotherapy.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

PREVENTION

Masking

NONE

Intervention model description

Kanglaite injection + Radiotherapy ± Chemotherapy

Eligibility

Sex/Gender

ALL

Age

18 Years to 80 Years

Healthy volunteers

Inclusion criteria

1. 18-80 years old, expected survival period ≥ 12 months 2. Karnofsky score ≥80 points 3. 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 4. with or without induction chemotherapy (induced chemotherapy ≤ 3 cycles); 5. 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 6. Sign informed consent.

Exclusion criteria

1. Distant metastases 2. Allergy to Kanglaite 3. Head and neck had previously received radiation therapy 4. Pregnancy or lactation patients 5. Targeted drug therapy during radiotherapy 6. Radio-chemotherapy uses cytotoxic drugs other than platinum 7. 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 8. Mental history, can not cooperate with the treatment 9. Researchers believe unsuitable to participate in this trial.

Design outcomes

Primary

Measure	Time frame	Description
the Incidence Rate of Severe Radiation Mucositis	From date of randomization until the end radiotherapy, up to 3 months.	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.

Secondary

Measure	Time frame	Description
the Incidence Rate of Non-Hematologic Toxicity Side Events	From date of randomization until the end radiotherapy, up to 3 months.	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.
the Incidence Rate of Hematologic Toxicity Side Events	From date of randomization until the end radiotherapy, up to 3 months.	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.
the Nutritional Status	From date of randomization until the end radiotherapy, up to 3 months.	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.
the Overall Quality of Life (QOL)	From date of randomization until the end radiotherapy, up to 3 months.	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.
Quality of Life Specific to Head and Neck Cancers	From date of randomization until the end radiotherapy, up to 3 months.	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.

Countries

China

Participant flow

Recruitment details

We recruited patients with head and neck cancer receiving radiotherapy in the First Affiliated Hospital of Harbin Medical University between January 2017 and October 2019.

Pre-assignment details

Sixty-two patients were assessed for eligibility. Three patients did not meet the inclusion criteria, and six patients declined to participate.

Participants by arm

Arm	Count
Kanglaite Group Kanglaite injection was used during radiotherapy	46
Total	46

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	patient's information was incomplete	1
Overall Study	Protocol Violation	2
Overall Study	Withdrawal by Subject	4

Baseline characteristics

Characteristic	Kanglaite Group	—
Age, Categorical <=18 years	0 Participants	—
Age, Categorical >=65 years	12 Participants	—
Age, Categorical Between 18 and 65 years	34 Participants	—
Nutritional status Good nourishment	6 Participants	—
Nutritional status Severe malnutrition	9 Participants	—
Nutritional status Suspected or moderate malnutrition	31 Participants	—
Overall quality of life (QOL) appetite loss	14.81 units on a scale STANDARD_DEVIATION 25.18	—
Overall quality of life (QOL) cognitive functioning	81.46 units on a scale STANDARD_DEVIATION 25.92	—
Overall quality of life (QOL) constipation	10.36 units on a scale STANDARD_DEVIATION 21.1	—
Overall quality of life (QOL) diarrhoea	8.88 units on a scale STANDARD_DEVIATION 16.51	—
Overall quality of life (QOL) dyspnoea	12.59 units on a scale STANDARD_DEVIATION 22.79	—
Overall quality of life (QOL) emotional functioning	84.48 units on a scale STANDARD_DEVIATION 18.36	—
Overall quality of life (QOL) fatigue	21.40 units on a scale STANDARD_DEVIATION 19.34	—
Overall quality of life (QOL) global QOL	73.18 units on a scale STANDARD_DEVIATION 25.39	—
Overall quality of life (QOL) insomnia	14.07 units on a scale STANDARD_DEVIATION 27.05	—
Overall quality of life (QOL) nausea and vomiting	4.07 units on a scale STANDARD_DEVIATION 12.38	—
Overall quality of life (QOL) pain	16.3 units on a scale STANDARD_DEVIATION 19.29	—
Overall quality of life (QOL) physical functioning	89.99 units on a scale STANDARD_DEVIATION 12.05	—
Overall quality of life (QOL) role functioning	82.6 units on a scale STANDARD_DEVIATION 24.33	—
Overall quality of life (QOL) social functioning	71.1 units on a scale STANDARD_DEVIATION 30.02	—
Quality of life specific to head and neck cancers coughing	22.22 units on a scale STANDARD_DEVIATION 28.42	—
Quality of life specific to head and neck cancers dry mouth	22.22 units on a scale STANDARD_DEVIATION 26.59	—
Quality of life specific to head and neck cancers feeling ill	22.22 units on a scale STANDARD_DEVIATION 27.52	—
Quality of life specific to head and neck cancers less sexuality	17.55 units on a scale STANDARD_DEVIATION 30.89	—
Quality of life specific to head and neck cancers mouth opening problem	11.58 units on a scale STANDARD_DEVIATION 24.77	—
Quality of life specific to head and neck cancers pain	19.22 units on a scale STANDARD_DEVIATION 25.15	—
Quality of life specific to head and neck cancers sensory problems	9.25 units on a scale STANDARD_DEVIATION 22.34	—
Quality of life specific to head and neck cancers social contact problems	9.48 units on a scale STANDARD_DEVIATION 19.7	—
Quality of life specific to head and neck cancers social eating problems	14.43 units on a scale STANDARD_DEVIATION 25.95	—
Quality of life specific to head and neck cancers speech problems	25.67 units on a scale STANDARD_DEVIATION 29.28	—
Quality of life specific to head and neck cancers sticky saliva	30.36 units on a scale STANDARD_DEVIATION 31.64	—
Quality of life specific to head and neck cancers swallowing	16.62 units on a scale STANDARD_DEVIATION 24.08	—
Quality of life specific to head and neck cancers teeth	24.44 units on a scale STANDARD_DEVIATION 32.09	—
Race and Ethnicity Not Collected	—	— Participants
Region of Enrollment China	46 participants	—
Sex: Female, Male Female	7 Participants	—
Sex: Female, Male Male	39 Participants	—

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 46
other Total, other adverse events	34 / 46
serious Total, serious adverse events	7 / 46

Outcome results

Primary

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.