Oral Mucositis, Stomatitis
Conditions
Brief summary
Oral mucositis (OM) is a common and debilitating toxicity induced by many chemotherapy (CT) regimens and by radiation to the head and neck. The purpose of this study is to determine the effectiveness of SNX-1012 in decreasing the duration of Grade 2, 3, or 4 oral mucositis (OM) according to World Health Organization (WHO) criteria.
Interventions
DRUGSNX-1012 (meclocycline sulfosalicylate)
tablets to be dissolved in water for oral swish and expectorate; 30 mg, 4 times daily for 10 days
DRUGplacebo
Tablets to be dissolved in water for oral swish and expectorate; placebo, 4 times daily for 10 days
Sponsors
Mucosal Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed written informed consent * Naive to focal radiation therapy in the head and neck regions for cancer prior to CT Cycle 1. Subjects with prior or concomitant radiation therapy to areas other than the head and neck may be enrolled. * Histologically confirmed diagnosis of breast or lung cancer (NSCLC or SCLC) * Chemotherapy regimen containing AC ± T or EC ± T (for breast cancer), cisplatin or carboplatin (for NSCLC or SCLC), or doxorubicin (for SCLC) * Subjects will receive the same regimen and dose of CT in the OM Treatment CT Cycle as was administered in the immediately preceding CT Cycle. * Subjects will have had OM of WHO Grade of greater than or equal to 2 during CT Cycle 1 or Cycle 2 * Subjects 18 years and older * Karnofsky Performance Score \>=60 * Baseline laboratory assessments: Hemoglobin (Hgb) level \>= 9 g/dL Absolute neutrophil count (ANC) \>= 1.5 x 10 to the 9/L Platelet count \>= 100 x 10 to the 9/L Serum bilirubin level \<= 1.5 times institutional upper limit of normal (ULN) Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) level \<= 2 times above ULN * Females of childbearing potential must have a negative serum or urine pregnancy test result at the screening visit prior to the start of Cycle 1 and at the visit scheduled for \<= 48 hours prior to the start of the OM Treatment CT Cycle * Subjects with reproductive capability must agree to practice adequate contraception methods (males must use condoms or be surgically sterilized; females must be surgically sterilized, post-menopausal for at least 1 year, or use an appropriate double barrier method, prescribed birth control oral contraceptive, patch, implant, or injection during the course of the study and for up to 30 days after completion of study assessments) * Absence of other serious concurrent medical illness * Psychologically able to participate and comply with study requirements
Exclusion criteria
* Prior history of oral mucositis with previous chemotherapy treatment * Previous treatment with an anthracycline agent (other than low-dose neoadjuvant therapy) * Active liver disease or serum AST and/or ALT level \> 2 times above ULN * Currently receiving an investigational agent, planning to receive an investigational agent during the study period, or received an investigational agent within 30 days of the first dose of SNX-1012 * Use of an immunosuppressive regimen of systemic corticosteroids * Unwilling/unable to receive periodic oral assessments by a study evaluator or unable to complete the daily self-reported outcome questionnaire * Pregnant or breast-feeding women * Bronchoalveolar carcinoma * Metastases to the central nervous system * Prior or planned focal radiation therapy in the head or neck regions for the treatment of cancer (prior radiation to areas other than the head and neck is permitted) * Presence of active or history of chronic oral mucosal disease * Presence or history of any other primary malignancy (curatively treated nonmelanoma skin cancer is allowed) * History of chronic liver disease * Active hepatitis A or B * Unable to receive CT during the OM Treatment CT Cycle at the same regimen and/or dose as in the immediately preceding CT cycle. * Known sensitivity to tetracyclines * Known to be seropositive for HIV or HCV * Use of an immunosuppressive regimen of systemic corticosteroids. * Current alcohol dependence or drug abuse * Psychological, social or familial or geographical reasons that would hinder or prevent study visits * Compromised ability to give written informed consent and/or to comply with study procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Ulcerative Oral Mucositis | At least 10 consecutive days beginning on Day 1 of a chemotherapy cycle | All randomized subjects were directly observed by trained evaluators for at least 10 consecutive days during the chemotherapy cycle to document the duration for those that developed recurrent ulcerative oral mucositis |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Ulcerative Oral Mucositis | At least 10 consecutive days beginning on Day 1 of a chemotherapy cycle | All randomized subjects were directly observed by trained evaluators for at least 10 consecutive days during the chemotherapy cycle to identify recurrence of ulcerative oral mucositis. |
Countries
India, United States
Participant flow
Pre-assignment details
533 subjects were screened during a chemotherapy cycle and those that developed ulcerative oral mucositis and fully recovered were randomized to treatment with study drug during the next chemotherapy cycle
Participants by arm
| Arm | Count |
|---|---|
| SNX-1012 SNX-1012 (meclocycline sulfosalicylate) tablets dissolved in water for oral swish and expectorate; 30 mg, 4 times daily for 10 days | 57 |
| Placebo Placebo tablets (matched to SNX-1012) dissolved in water for oral swish and expectorate; 4 times daily for 10 days | 24 |
| Total | 81 |
Baseline characteristics
| Characteristic | SNX-1012 | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 9 Participants | 6 Participants | 15 Participants |
| Age, Categorical Between 18 and 65 years | 48 Participants | 18 Participants | 66 Participants |
| Age Continuous | 51.3 years STANDARD_DEVIATION 12.9 | 54.5 years STANDARD_DEVIATION 12 | 52.3 years STANDARD_DEVIATION 12.6 |
| Region of Enrollment India | 18 participants | 7 participants | 25 participants |
| Region of Enrollment United States | 39 participants | 17 participants | 56 participants |
| Sex: Female, Male Female | 53 Participants | 24 Participants | 77 Participants |
| Sex: Female, Male Male | 4 Participants | 0 Participants | 4 Participants |
Outcome results
Primary
Duration of Ulcerative Oral Mucositis
All randomized subjects were directly observed by trained evaluators for at least 10 consecutive days during the chemotherapy cycle to document the duration for those that developed recurrent ulcerative oral mucositis
Time frame: At least 10 consecutive days beginning on Day 1 of a chemotherapy cycle
Population: Analysis only includes subjects randomized to the 30mg dose of SNX-1012
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SNX-1012 | Duration of Ulcerative Oral Mucositis | 2.3 Days | Standard Deviation 3.04 |
| Placebo | Duration of Ulcerative Oral Mucositis | 3.2 Days | Standard Deviation 4.68 |
Secondary
Number of Participants With Ulcerative Oral Mucositis
All randomized subjects were directly observed by trained evaluators for at least 10 consecutive days during the chemotherapy cycle to identify recurrence of ulcerative oral mucositis.
Time frame: At least 10 consecutive days beginning on Day 1 of a chemotherapy cycle
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SNX-1012 | Number of Participants With Ulcerative Oral Mucositis | 22 Participants |
| Placebo | Number of Participants With Ulcerative Oral Mucositis | 11 Participants |