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

Head and Neck Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03101514
• Other study ID #: 201708
• Status: Completed
• Phase: Phase 2
• Start date: January 1, 2017
• Est. completion date: February 1, 2021

Study information

• Verified date: February 2021
• Source: First Affiliated Hospital of Harbin Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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%.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: February 1, 2021
• Est. primary completion date: February 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Head and Neck Cancer
• Head and Neck Neoplasms
• Radiotherapy

Intervention

Drug:
• Kanglaite
Kanglaite injection 200ml is injected intravenous from the first day to the last day of radiotherapy.
• chemotherapy
Cisplatin 80-100mg/m2 was used every 3 weeks during radiotherapy.

Locations

Country	Name	City	State
China	First Affiliated Hospital of Harbin Medical University	Harbin	Heilongjiang

Sponsors (1)

Lead Sponsor	Collaborator
First Affiliated Hospital of Harbin Medical University

Country where clinical trial is conducted

China, 

References & Publications (7)

Chen Y, Liu MZ, Liang SB, Zong JF, Mao YP, Tang LL, Guo Y, Lin AH, Zeng XF, Ma J. Preliminary results of a prospective randomized trial comparing concurrent chemoradiotherapy plus adjuvant chemotherapy with radiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma in endemic regions of china. Int J Radiat Oncol Biol Phys. 2008 Aug 1;71(5):1356-64. doi: 10.1016/j.ijrobp.2007.12.028. Epub 2008 May 9. — View Citation

Harris DJ. Cancer treatment-induced mucositis pain: strategies for assessment and management. Ther Clin Risk Manag. 2006 Sep;2(3):251-8. — View Citation

Redding SW. Cancer therapy-related oral mucositis. J Dent Educ. 2005 Aug;69(8):919-29. — View Citation

Rodríguez-Caballero A, Torres-Lagares D, Robles-García M, Pachón-Ibáñez J, González-Padilla D, Gutiérrez-Pérez JL. Cancer treatment-induced oral mucositis: a critical review. Int J Oral Maxillofac Surg. 2012 Feb;41(2):225-38. doi: 10.1016/j.ijom.2011.10.011. Epub 2011 Nov 8. Review. — View Citation

Silverman S Jr. Diagnosis and management of oral mucositis. J Support Oncol. 2007 Feb;5(2 Suppl 1):13-21. Review. — View Citation

Trotti A, Bellm LA, Epstein JB, Frame D, Fuchs HJ, Gwede CK, Komaroff E, Nalysnyk L, Zilberberg MD. Mucositis incidence, severity and associated outcomes in patients with head and neck cancer receiving radiotherapy with or without chemotherapy: a systematic literature review. Radiother Oncol. 2003 Mar;66(3):253-62. Review. — View Citation

Walsh L, Gillham C, Dunne M, Fraser I, Hollywood D, Armstrong J, Thirion P. Toxicity of cetuximab versus cisplatin concurrent with radiotherapy in locally advanced head and neck squamous cell cancer (LAHNSCC). Radiother Oncol. 2011 Jan;98(1):38-41. doi: 10.1016/j.radonc.2010.11.009. Epub 2010 Dec 13. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	From date of randomization until the end radiotherapy, up to 3 months.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.

External Links

•   Guo Y, Li DP. Protective effects of Kanglaite injection on hematopoiesis and liver and kidney damage caused by three anticancer drugs. Chinese journal of modern applied phaemacy.1998;15(6):61-62(in Chinese).
•   Jing JL, Li XL, Nan YQ. Advances in the study of the effect of Kanglaite injection on tumor therapy. Chinese Remedies & Clinics, 2013;13(11):1447-1448 (in Chinese).
•   Ren ZP, et al. The therapeutic effects of the combined therapy with kanglaite injection and radiotherapy on nasopharyngea carcinoma among aged cases. Chinese Journal of Otorhinolaryngology of Integrated Traditional and Western Medici 2005;13(6)
•   Wang WD, Sun SP, Wang XD. Influence of KLT on Radiotherapy Effect of Patients with Advanced Nasopharyngeal Carcinoma. China Journal of Cancer Prevention and Treatment,2003:10(6): 635-637(in Chinese).