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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Oral Mucositis

Intervention / Treatment
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* Drug: 0.25% EISO mouth rinse


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. At least 18 years of age Estimated survival of at least 6 months. 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 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. Are willing to refrain from using other treatments for oral mucositis until they consult with the study investigator(s). 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: Have preexisting mucositis from other causes. Are immunosuppressed or in chronic use of immunosuppressive drugs. 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.). Eastern Cooperative Oncology Group (ECOG) performance status > 3 Unwilling or unable to follow the protocol requirements. Have any condition that in the opinion of the investigator would confound the efficacy, safety and tolerability assessments, such as oral thrush. Have participated in any clinical trial in the previous 30 days. Are pregnant, breastfeeding, or unwilling to practice an acceptable form of birth control during the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 0.25% EISO Mouth Rinse<br>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<br>* A mouth rinse to be used three times a day during the course of radiation and/or chemotherapy to prevent or minimize oral mucositis<br>* Other names: East Indian sandalwood oil, Albuterpenoids;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients Achieving Less Than or Equal to 2 RTOG Score At Visit 9 | 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 | Up to ten (10) weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subject Self Reporting Burning or Irritation | Calculated by the number and percentage of subjects self reporting irritation of grade 1 (mild) or higher. | Up to ten (10) weeks | 
| NRPS (Numerical Rating Pain Scale) | 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. | Up to ten (10) weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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radiation therapy, chemotherapy, head and neck cancer