A Trial of a Botanical Drug Containing East Indian Sandalwood Oil (EISO) for the Treatment of Oral Mucositis

• Sponsor: Santalis Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02399228
• Collaborator: The University of Texas Health Science Center at San Antonio (Other)
• Enrollment: 13
• Location: 1
• Arm: 1
• Actual Duration (Months): 19.5
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The initial proposed clinical study will be conducted in adult head and neck cancer subjects. This will be an open-labeled, proof of concept trial to evaluate the efficacy, safety and tolerability of EISO in a form of oral rinse as adjunctive therapy to standard of care. Santalis believes that the proposed study is a prudent and appropriate approach to investigate the potential of their product to prevent or improve oral mucositis symptoms commonly seen in subjects undergoing radiotherapy with or without chemotherapy.

Condition or Disease	Intervention/Treatment	Phase
Oral Mucositis	Drug: 0.25% EISO mouth rinse	Phase 2

Detailed Description

The objectives of this proof of concept trial are: to evaluate the efficacy, safety and tolerability of SAN005 when administered to adults for the prevention and treatment of radiation induced oral mucositis.

Subjects will be instructed on the administration of study medication thrice daily till oral mucositis resolves. Subjects will return to the clinic once a week while receiving radiation and then once every two weeks once their radiation has been completed and then until their mucositis has resolved for the Final Study Visit.

Preliminary Efficacy Evaluation will be the severity of pain rated by the Numeric Pain Rating Scale (NRPS) and mucositis grade by Radiation Therapy Oncology Group (RTOG) criteria at Visit 7 (Day 36). Additional secondary efficacy evaluations will include the severity of pain rated by the NRPS and mucositis grade by RTOG criteria at each study visit, frequency of the percutaneous endoscopic gastrostomy (PEG) tube for feeding during the duration of treatment and weight loss from baseline through Visit 5 and 7. The time of mucositis onset and duration will also be used in assessing efficacy. Additional secondary and exploratory endpoints will be outlined in the statistical analysis plan. The overall efficacy is determined by comparing the data to historical controls. Safety will be assessed by evaluating adverse events (AEs) with respect to severity, duration, and relationship to study drug. In addition, tolerability evaluations will be performed at each study visit.

Study Design

• Study Type: Interventional
• Actual Enrollment: 13 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: An Open-Label, Proof of Concept, Efficacy, Safety and Tolerability Trial of a Botanical Drug Containing East Indian Sandalwood Oil (EISO) for the Prevention and Treatment of Oral Mucositis Induced by Radiation Therapy
• Actual Study Start Date: Oct 4, 2015
• Actual Primary Completion Date: May 20, 2017
• Actual Study Completion Date: May 20, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 0.25% EISO Mouth Rinse A mouth rinse containing 0.25% East Indian sandalwood oil (EISO), a candidate botanical drug substance. The rinse will be used three times a day for up to ten weeks. The material will not be ingested but used to "swish, gargle and spit".	Drug: 0.25% EISO mouth rinse; A mouth rinse to be used three times a day during the course of radiation and/or chemotherapy to prevent or minimize oral mucositis; Other Names: East Indian sandalwood oil, Albuterpenoids

Outcome Measures

Primary Outcome Measures

1. Patients Achieving Less Than or Equal to "2" RTOG Score At Visit 9 [Up to ten (10) weeks]

   The Radiation Therapy Oncology Group (RTOG) is the measure of anatomical changes associated with oral mucositis. Patients scores will be compared to historical data of patient progression. RTOG Scoring Criteria- Grade 0(none)- No change over baseline Grade 1(mild)- Irritation, may experience slight pain, not requiring analgesic Grade 2(moderate)- Patchy mucositis that may produce inflammatory serosanguinitis discharge; may experience moderate pain requiring analgesia Grade 3(severe) -Confluent, fibrinous mucositis, may include severe pain requiring narcotic Grade 4(life-threatening)-Ulceration, hemorrhage, or necrosis

Secondary Outcome Measures

1. Subject Self Reporting Burning or Irritation [Up to ten (10) weeks]

   Calculated by the number and percentage of subjects self reporting irritation of grade 1 (mild) or higher.

2. NRPS (Numerical Rating Pain Scale) [Up to ten (10) weeks]

   Severity of pain in the oral cavity/oropharynx was measured using the numerical rating pain scale (NRPS) at each study visit. The NRPS is an 11-point scale from 0-10: 0 = No pain 10 = The most intense pain imaginable.

Other Outcome Measures

1. Safety Will be Assessed Based on the Frequency and Severity of Adverse Events. [[ Time Frame: Up to ten (10) weeks ]]

   Adverse Events (AEs) will be assessed in accordance the Common Terminology Criteria for Adverse Events (CTCAE). The number of patients experiencing adverse events possibly, or probably related to the study product will be reported. Possibly related: A clinical event, including laboratory test abnormality (if applicable), with a reasonable time sequence to administration of the drug, but which could also be explained by concurrent disease or other drugs or chemicals. Probably related: A clinical event, including laboratory test abnormality (if applicable), with a reasonable time sequence to administration of the drug, unlikely to be attributed to concurrent disease or other drugs or chemicals, and which follows a clinically reasonable response on withdrawal.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Subjects with head and neck cancer involving the oropharynx or oral cavity, who are expected to undergo high dose radiation therapy (i.e., ≥ 60 Gy) that typically results in oral mucositis, with or without concurrent chemotherapy or biologic targeted therapy.

2. At least 18 years of age

3. Estimated survival of at least 6 months.

4. No prior radiation therapy to the head and neck area, and no chemotherapy within the last year except for induction chemotherapy delivered (or to be delivered) prior to the current course of radiation therapy

5. Female subjects of child-bearing potential must agree to use an adequate form of contraceptive (e.g., hormonal, barrier method or abstinence) prior to study entry and for the duration of the trial.

6. Are willing to refrain from using other treatments for oral mucositis until they consult with the study investigator(s).

7. Are able to give written informed consent in a manner approved by the Institutional Review Board and comply with the requirements of the study.

Exclusion Criteria:

1. Have preexisting mucositis from other causes.

2. Are immunosuppressed or in chronic use of immunosuppressive drugs.

3. Have a known sensitivity to any of the constituents of the test product including sensitivities to sandalwood oil, fragrances or any member of the Compositae family of vascular plants (e.g., sunflowers, daisies, dahlias, etc.).

4. Eastern Cooperative Oncology Group (ECOG) performance status > 3

5. Unwilling or unable to follow the protocol requirements.

6. Have any condition that in the opinion of the investigator would confound the efficacy, safety and tolerability assessments, such as oral thrush.

7. Have participated in any clinical trial in the previous 30 days.

8. Are pregnant, breastfeeding, or unwilling to practice an acceptable form of birth control during the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UTHSCSA Cancer Therapy and Research Center (CTRC)	San Antonio	Texas	United States	78229

Sponsors and Collaborators

• Santalis Pharmaceuticals, Inc.
• The University of Texas Health Science Center at San Antonio

Investigators

• Study Director: Paul Castella, PhD, Santalis Pharmaceuticals

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 27, 2015
• Informed Consent Form - Mar 15, 2017

More Information

Publications

• Rosenthal DI, Trotti A. Strategies for managing radiation-induced mucositis in head and neck cancer. Semin Radiat Oncol. 2009 Jan;19(1):29-34. doi: 10.1016/j.semradonc.2008.09.006. Review.
• Singh CU NJ, inventors. : Derivatives of sandalwood oil and santalols for treating cold sores and herpes. . US patent application publication US2008/0058413 A1. 06 2008

• Responsible Party: Santalis Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT02399228
• Other Study ID Numbers: SAN005-01
• First Posted: Mar 26, 2015
• Last Update Posted: Nov 19, 2021
• Last Verified: Nov 1, 2021

• Keywords provided by Santalis Pharmaceuticals, Inc.: radiation therapy; chemotherapy; head and neck cancer
• Additional relevant MeSH terms: Mucositis; Stomatitis

Study Results

Participant Flow

Arm/Group Title	0.25% EISO Mouth Rinse
Arm/Group Description	A mouth rinse containing 0.25% East Indian sandalwood oil (EISO), a candidate botanical drug substance. The rinse will be used three times a day for up to ten weeks. The material will not be ingested but used to "swish, gargle and spit". 0.25% EISO mouth rinse: A mouth rinse to be used three times a day during the course of radiation and/or chemotherapy to prevent or minimize oral mucositis
Period Title: Overall Study
STARTED	13
COMPLETED	7
NOT COMPLETED	6

Baseline Characteristics

Arm/Group Title	0.25% EISO Mouth Rinse
Arm/Group Description	A mouth rinse containing 0.25% East Indian sandalwood oil (EISO), a candidate botanical drug substance. The rinse will be used three times a day for up to ten weeks. The material will not be ingested but used to "swish, gargle and spit". 0.25% EISO mouth rinse: A mouth rinse to be used three times a day during the course of radiation and/or chemotherapy to prevent or minimize oral mucositis
Overall Participants	13
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	10 76.9%
>=65 years	3 23.1%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	55.4
Sex: Female, Male (Count of Participants)
Female	2 15.4%
Male	11 84.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	12 92.3%
Unknown or Not Reported	1 7.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	12 92.3%
More than one race	0 0%
Unknown or Not Reported	1 7.7%
Region of Enrollment (Count of Participants)
United States	13 100%

Outcome Measures

1. Primary Outcome

Title	Patients Achieving Less Than or Equal to "2" RTOG Score At Visit 9
Description	The Radiation Therapy Oncology Group (RTOG) is the measure of anatomical changes associated with oral mucositis. Patients scores will be compared to historical data of patient progression. RTOG Scoring Criteria- Grade 0(none)- No change over baseline Grade 1(mild)- Irritation, may experience slight pain, not requiring analgesic Grade 2(moderate)- Patchy mucositis that may produce inflammatory serosanguinitis discharge; may experience moderate pain requiring analgesia Grade 3(severe) -Confluent, fibrinous mucositis, may include severe pain requiring narcotic Grade 4(life-threatening)-Ulceration, hemorrhage, or necrosis
Time Frame	Up to ten (10) weeks

Outcome Measure Data

Analysis Population Description

Not all subjects analyzed at visit 9 completed the trial. Therefore, the number of completed subjects (7) is less than the number of subjects analyzed for this endpoint.

Arm/Group Title	0.25% EISO Mouth Rinse
Arm/Group Description	A mouth rinse containing 0.25% East Indian sandalwood oil (EISO), a candidate botanical drug substance. The rinse will be used three times a day for up to ten weeks. The material will not be ingested but used to "swish, gargle and spit". 0.25% EISO mouth rinse: A mouth rinse to be used three times a day during the course of radiation and/or chemotherapy to prevent or minimize oral mucositis
Measure Participants	7
Count of Participants [Participants]	7 53.8%

2. Secondary Outcome

Title	Subject Self Reporting Burning or Irritation
Description	Calculated by the number and percentage of subjects self reporting irritation of grade 1 (mild) or higher.
Time Frame	Up to ten (10) weeks

Outcome Measure Data

Analysis Population Description

All subjects who reported tolerability at any point during the study were analyzed

Arm/Group Title	0.25% EISO Mouth Rinse
Arm/Group Description	A mouth rinse containing 0.25% East Indian sandalwood oil (EISO), a candidate botanical drug substance. The rinse will be used three times a day for up to ten weeks. The material will not be ingested but used to "swish, gargle and spit". 0.25% EISO mouth rinse: A mouth rinse to be used three times a day during the course of radiation and/or chemotherapy to prevent or minimize oral mucositis
Measure Participants	13
None	4 30.8%
Mild	4 30.8%
Moderate	3 23.1%
Severe	2 15.4%

3. Secondary Outcome

Title	NRPS (Numerical Rating Pain Scale)
Description	Severity of pain in the oral cavity/oropharynx was measured using the numerical rating pain scale (NRPS) at each study visit. The NRPS is an 11-point scale from 0-10: 0 = No pain 10 = The most intense pain imaginable.
Time Frame	Up to ten (10) weeks

Outcome Measure Data

Analysis Population Description

ITT (Intention-to-treat)

Arm/Group Title	0.25% EISO Mouth Rinse
Arm/Group Description	A mouth rinse containing 0.25% East Indian sandalwood oil (EISO), a candidate botanical drug substance. The rinse will be used three times a day for up to ten weeks. The material will not be ingested but used to "swish, gargle and spit". 0.25% EISO mouth rinse: A mouth rinse to be used three times a day during the course of radiation and/or chemotherapy to prevent or minimize oral mucositis
Measure Participants	13
Mean (Standard Deviation) [score on a scale]	3.875 (2.75)

4. Other Pre-specified Outcome

Title	Safety Will be Assessed Based on the Frequency and Severity of Adverse Events.
Description	Adverse Events (AEs) will be assessed in accordance the Common Terminology Criteria for Adverse Events (CTCAE). The number of patients experiencing adverse events possibly, or probably related to the study product will be reported. Possibly related: A clinical event, including laboratory test abnormality (if applicable), with a reasonable time sequence to administration of the drug, but which could also be explained by concurrent disease or other drugs or chemicals. Probably related: A clinical event, including laboratory test abnormality (if applicable), with a reasonable time sequence to administration of the drug, unlikely to be attributed to concurrent disease or other drugs or chemicals, and which follows a clinically reasonable response on withdrawal.
Time Frame	[ Time Frame: Up to ten (10) weeks ]

Outcome Measure Data

Analysis Population Description

Only 4 patients reported adverse events possibly or probably related to the study product.

Arm/Group Title	0.25% EISO Mouth Rinse
Arm/Group Description	A mouth rinse containing 0.25% East Indian sandalwood oil (EISO), a candidate botanical drug substance. The rinse will be used three times a day for up to ten weeks. The material will not be ingested but used to "swish, gargle and spit". 0.25% EISO mouth rinse: A mouth rinse to be used three times a day during the course of radiation and/or chemotherapy to prevent or minimize oral mucositis
Measure Participants	13
Nausea (Mild)	2 15.4%
Vomiting (Mild)	2 15.4%

Adverse Events

Time Frame	Over the course of the treatment (up to 10 weeks), which was while the patients were undergoing radiotherapy and chemo.
Adverse Event Reporting Description	Adverse events were solicited from subjects through clinic visits and captured on daily diaries
Arm/Group Title	0.25% EISO Mouth Rinse
Arm/Group Description	A mouth rinse containing 0.25% East Indian sandalwood oil (EISO), a candidate botanical drug substance. The rinse will be used three times a day for up to ten weeks. The material will not be ingested but used to "swish, gargle and spit". 0.25% EISO mouth rinse: A mouth rinse to be used three times a day during the course of radiation and/or chemotherapy to prevent or minimize oral mucositis
All Cause Mortality
	0.25% EISO Mouth Rinse
	Affected / at Risk (%)	# Events
Total	0/13 (0%)
Serious Adverse Events
	0.25% EISO Mouth Rinse
	Affected / at Risk (%)	# Events
Total	0/13 (0%)
Other (Not Including Serious) Adverse Events
	0.25% EISO Mouth Rinse
	Affected / at Risk (%)	# Events
Total	10/13 (76.9%)
Ear and labyrinth disorders
Ear Pain	2/13 (15.4%)	2
Eye disorders
Otitis Externa	1/13 (7.7%)	1
Otitis Media	1/13 (7.7%)	1
Gastrointestinal disorders
Nausea	6/13 (46.2%)	6
Vomiting Grade 1	3/13 (23.1%)	3
Dyspepsia	2/13 (15.4%)	2
General disorders
Dysgeusia	6/13 (46.2%)	6
Dry Mouth	5/13 (38.5%)	5
Fatigue	5/13 (38.5%)	5
Weight Loss	4/13 (30.8%)	4
Dysphagia	3/13 (23.1%)	3
Insomnia	3/13 (23.1%)	3
Cough	2/13 (15.4%)	2
Hypoalbuminemia	2/13 (15.4%)	2
Hypomagnesemia	2/13 (15.4%)	2
Hyponatremia	2/13 (15.4%)	2
Oral Pain	2/13 (15.4%)	2
Sore Throat	2/13 (15.4%)	2
Chills	1/13 (7.7%)	1
Constipation	1/13 (7.7%)	1
Dizziness	1/13 (7.7%)	1
Epistaxis	1/13 (7.7%)	1
Hypokalemia	1/13 (7.7%)	1
Immune system disorders
Lymphocyte count decreased	2/13 (15.4%)	2
Mucosal Infection	2/13 (15.4%)	2
White Blood Cell Decreased	2/13 (15.4%)	2
Neutrophil Count Decreased	1/13 (7.7%)	1
Platelet Count Decreased	1/13 (7.7%)	1
Metabolism and nutrition disorders
Anemia	2/13 (15.4%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor Pain	1/13 (7.7%)	1
Psychiatric disorders
Memory Impairment	1/13 (7.7%)	1
Renal and urinary disorders
Creatinine Increased	2/13 (15.4%)	2
Hypocalcemia	2/13 (15.4%)	2
Skin and subcutaneous tissue disorders
Dermatitis Radiation	4/13 (30.8%)	4
Mucositis	3/13 (23.1%)	3
Hyperpigmentation	1/13 (7.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.