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

• Sponsor: First Affiliated Hospital of Harbin Medical University (Other)
• Overall Status: Completed
• CT.gov ID: NCT03101514
• Collaborator: (none)
• Enrollment: 53
• Location: 1
• Arm: 1
• Actual Duration (Months): 49
• Patients Per Site Per Month: 1.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer; Radiotherapy	Drug: Kanglaite; Drug: chemotherapy	Phase 2

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%.

Study Design

• Study Type: Interventional
• Actual Enrollment: 53 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Kanglaite injection + Radiotherapy ± ChemotherapyKanglaite injection + Radiotherapy ± Chemotherapy
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Kanglaite Reduce the Toxicity of Radiotherapy of Head and Neck Cancer Phase II Study
• Actual Study Start Date: Jan 1, 2017
• Actual Primary Completion Date: Feb 1, 2021
• Actual Study Completion Date: Feb 1, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

1. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	First Affiliated Hospital of Harbin Medical University	Harbin	Heilongjiang	China	150001

Sponsors and Collaborators

• First Affiliated Hospital of Harbin Medical University

Investigators

• Principal Investigator: Zhi-Ping Liu, MD, First Affiliated Hospital of Harbin Medical University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 6, 2017

More Information

Additional Information:

• 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).
• 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).
• 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).
• 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)

Publications

• 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.
• Harris DJ. Cancer treatment-induced mucositis pain: strategies for assessment and management. Ther Clin Risk Manag. 2006 Sep;2(3):251-8.
• Redding SW. Cancer therapy-related oral mucositis. J Dent Educ. 2005 Aug;69(8):919-29.
• 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.
• Silverman S Jr. Diagnosis and management of oral mucositis. J Support Oncol. 2007 Feb;5(2 Suppl 1):13-21. Review.
• 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.
• 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.

• Responsible Party: First Affiliated Hospital of Harbin Medical University
• ClinicalTrials.gov Identifier: NCT03101514
• Other Study ID Numbers: 201708
• First Posted: Apr 5, 2017
• Last Update Posted: Jun 23, 2021
• Last Verified: Feb 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by First Affiliated Hospital of Harbin Medical University: head and neck; tumor; radiotherapy; mucositis; toxicity; Kanglaite injection
• Additional relevant MeSH terms: Head and Neck Neoplasms

Study Results

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

Arm/Group Title	Kanglaite Group
Arm/Group Description	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. There is no time interval requirement between Kanglaite and radiotherapy.
Period Title: Overall Study
STARTED	53
COMPLETED	46
NOT COMPLETED	7

Baseline Characteristics

Arm/Group Title	Kanglaite Group
Arm/Group Description	Kanglaite injection was used during radiotherapy
Overall Participants	46
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	34 73.9%
>=65 years	12 26.1%
Sex: Female, Male (Count of Participants)
Female	7 15.2%
Male	39 84.8%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (participants) [Number]
China	46 100%
Nutritional status (Count of Participants)
Severe malnutrition	9 19.6%
Suspected or moderate malnutrition	31 67.4%
Good nourishment	6 13%
Quality of life specific to head and neck cancers (units on a scale) [Mean (Standard Deviation) ]
pain	19.22 (25.15)
swallowing	16.62 (24.08)
sensory problems	9.25 (22.34)
speech problems	25.67 (29.28)
social eating problems	14.43 (25.95)
social contact problems	9.48 (19.70)
less sexuality	17.55 (30.89)
teeth	24.44 (32.09)
mouth opening problem	11.58 (24.77)
dry mouth	22.22 (26.59)
sticky saliva	30.36 (31.64)
coughing	22.22 (28.42)
feeling ill	22.22 (27.52)
Overall quality of life (QOL) (units on a scale) [Mean (Standard Deviation) ]
global QOL	73.18 (25.39)
physical functioning	89.99 (12.05)
role functioning	82.6 (24.33)
emotional functioning	84.48 (18.36)
cognitive functioning	81.46 (25.92)
social functioning	71.1 (30.02)
fatigue	21.40 (19.34)
nausea and vomiting	4.07 (12.38)
pain	16.3 (19.29)
dyspnoea	12.59 (22.79)
insomnia	14.07 (27.05)
appetite loss	14.81 (25.18)
constipation	10.36 (21.10)
diarrhoea	8.88 (16.51)

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Kanglaite Group
Arm/Group Description	Kanglaite 200ml is injected once a day from Monday to Friday during radiotherapy.
Measure Participants	46
Grade 1 mucositis	3 6.5%
Grade 2 mucositis	38 82.6%
Grade 3 mucositis	5 10.9%
Grade 4 mucositis	0 0%

2. Secondary Outcome

Title	the Incidence Rate of Non-Hematologic Toxicity Side Events
Description	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.
Time Frame	From date of randomization until the end radiotherapy, up to 3 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Kanglaite Group
Arm/Group Description	Kanglaite 200ml is injected once a day from Monday to Friday during radiotherapy.
Measure Participants	46
grade 1 superficial phlebitis	1 2.2%
grade 1 rash	1 2.2%
radiotherapy dose reduction	1 2.2%
irradiation field modification	0 0%
radiotherapy interruption	4 8.7%

3. Secondary Outcome

Title	the Incidence Rate of Hematologic Toxicity Side Events
Description	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.
Time Frame	From date of randomization until the end radiotherapy, up to 3 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Kanglaite Group
Arm/Group Description	Kanglaite 200ml is injected once a day from Monday to Friday during radiotherapy.
Measure Participants	46
grade 0	30 65.2%
grade 1-2	13 28.3%
grade 3-4	3 6.5%
grade 0	28 60.9%
grade 1-2	18 39.1%
grade 3-4	0 0%
grade 0	40 87%
grade 1-2	6 13%
grade 3-4	0 0%
grade 0	37 80.4%
grade 1-2	9 19.6%
grade 3-4	0 0%
grade 0	44 95.7%
grade 1-2	2 4.3%
grade 3-4	0 0%
grade 0	41 89.1%
grade 1-2	5 10.9%
grade 3-4	0 0%
grade 0	43 93.5%
grade 1-2	3 6.5%
grade 3-4	0 0%
grade 0	45 97.8%
grade 1-2	1 2.2%
grade 3-4	0 0%
grade 0	43 93.5%
grade 1-2	3 6.5%
grade 3-4	0 0%
grade 0	44 95.7%
grade 1-2	2 4.3%
grade 3-4	0 0%
grade 0	45 97.8%
grade 1-2	1 2.2%
grade 3-4	0 0%

4. Secondary Outcome

Title	the Nutritional Status
Description	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.
Time Frame	From date of randomization until the end radiotherapy, up to 3 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Kanglaite Group
Arm/Group Description	Kanglaite 200ml is injected once a day from Monday to Friday during radiotherapy.
Measure Participants	46
Score 0-1	2 4.3%
Score 2-8	13 28.3%
Score ≧9	31 67.4%

5. Secondary Outcome

Title	the Overall Quality of Life (QOL)
Description	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.
Time Frame	From date of randomization until the end radiotherapy, up to 3 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Kanglaite Group
Arm/Group Description	Kanglaite 200ml is injected once a day from Monday to Friday during radiotherapy.
Measure Participants	46
global quality of life during radiotherapy	56.52 (29.80)
physical functioning during radiotherapy	77.19 (21.66)
rolel functioning during radiotherapy	70.28 (27.42)
emotional functioning during radiotherapy	77.35 (22.07)
cognitive functioning during radiotherapy	74.99 (23.23)
social functioning during radiotherapy	62.68 (31.26)
fatigue during radiotherapy	32.32 (21.91)
nausea and vomiting during radiotherapy	22.07 (24.09)
pain during radiotherapy	34.05 (26.73)
dyspnoea during radiotherapy	21.01 (28.42)
insomnia during radiotherapy	31.15 (31.74)
appetite loss during radiotherapy	43.47 (32.10)
costipation during radiotherapy	26.08 (28.90)
diarrhoea during radiotherapy	12.31 (19.06)
global quality of life post radiotherapy	64.72 (24.93)
physical functioning post radiotherapy	81.09 (22.00)
role functioning post radiotherapy	75.58 (25.02)
emotional functioning post radiotherapy	97.4 (10.47)
cognitive functioning post radiotherapy	83.72 (20.72)
social functioning post radiotherapy	72.09 (27.39)
fatigue post radiotherapy	28.16 (23.30)
nausea and vomiting post radiotherapy	11.26 (19.08)
pain post radiotherapy	21.70 (23.43)
dyspnoea post radiotherapy	19.12 (31.82)
insomnia post radiotherapy	21.70 (30.67)
appetite post radiotherapy	39.53 (30.21)
constipation post radiotherapy	16.27 (23.42)
diarrhoea post radiotherapy	4.65 (11.68)

6. Secondary Outcome

Title	Quality of Life Specific to Head and Neck Cancers
Description	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.
Time Frame	From date of randomization until the end radiotherapy, up to 3 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Kanglaite Group
Arm/Group Description	Kanglaite 200ml is injected once a day from Monday to Friday during radiotherapy.
Measure Participants	46
pain during radiotherapy	41.83 (23.72)
swallowing during radiotherapy	42.03 (27.05)
sensory problems during radiotherapy	35.5 (26.89)
speech problems during radiotherapy	43.59 (36.51)
social eating problems during radiotherapy	40.57 (30.51)
social contact problems during radiotherapy	21.08 (25.52)
less sexuality during radiotherapy	41.86 (40.67)
teeth during radiotherapy	28.98 (34.14)
mouth opening problems during radiotherapy	27.53 (28.37)
dry mouth during radiotherapy	60.14 (29.49)
sticky saliva during radiotherapy	66.66 (26.29)
coughing during radiotherapy	42.75 (33.45)
feeling ill during radiotherapy	47.40 (27.05)
pain post radiotherapy	33.72 (26.11)
swallowing post radiotherapy	36.04 (23.40)
sensory problems post radiotherapy	36.04 (29.30)
speech problems post radiotherapy	38.49 (35.41)
social eating problems post radiotherapy	28.09 (24.60)
social contact problems post radiotherapy	11.99 (17.03)
less sexuality post radiotherapy	37.96 (38.34)
teeth post radiotherapy	23.25 (29.57)
mouth opening problems post radiotherapy	12.40 (17.85)
dry mouth post radiotherapy	53.48 (34.22)
sticky saliva post radiotherapy	56.58 (35.28)
coughing post radiotherapy	37.2 (33.49)
feeling ill post radiotherapy	37.20 (29.28)

Adverse Events

Time Frame	2 months
Arm/Group Title	Kanglaite Group
Arm/Group Description	Kanglaite 200ml is injected once a day from Monday to Friday during radiotherapy.
All Cause Mortality
	Kanglaite Group
	Affected / at Risk (%)	# Events
Total	0/46 (0%)
Serious Adverse Events
	Kanglaite Group
	Affected / at Risk (%)	# Events
Total	7/46 (15.2%)
Blood and lymphatic system disorders
Neutropenia	3/46 (6.5%)
Skin and subcutaneous tissue disorders
mucositis	5/46 (10.9%)
Other (Not Including Serious) Adverse Events
	Kanglaite Group
	Affected / at Risk (%)	# Events
Total	34/46 (73.9%)
Blood and lymphatic system disorders
anemia	18/46 (39.1%)
Neutropenia	13/46 (28.3%)
Thrombocytopenia	6/46 (13%)
General disorders
Pre-albumin	9/46 (19.6%)
Hepatobiliary disorders
Alanine aminotransferase	5/46 (10.9%)
Glutamic oxaloacetic transaminase	3/46 (6.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.