A Phase 1b, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of ST-617 for the Attenuation of Oral Mucositis in Patients Receiving Chemoradiation for Head and Neck Cancer
- Conditions
- Oral MucositisHead and Neck CancerCancer - Head and neckOral and Gastrointestinal - Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
- Registration Number
- ACTRN12620000541909
- Lead Sponsor
- PSI CRO Australia Pty. Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 134
Patient Inclusion Criteria
Each patient must meet all the following criteria to participate in the study:
1. Histopathologically confirmed squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or nasopharynx.
2. Unknown Human Papillomavirus (HPV) positive primaries thought to be of oropharyngeal origin may be included if other inclusion criteria are met.
3. Documentation of HPV status for tumors of the oropharynx, tonsils or base of tongue. HPV status is determined by testing of the tumor (not an oral swab).
4. Planned therapy to include a continuous course of external beam radiation to include intensity-modulated radiotherapy (IMRT) with concurrent cisplatin monotherapy administered every week (30-40 mg/m2 for 6-7 doses) or every 3-weeks (60-100 mg/m2 for 3 doses).
5. Planned total radiation dose of between 60-72 Gy administered in single daily fractions of 2.0-2.2 Gy.
6. Radiation field must include at least 2 mucosal sites within the oral cavity (buccal mucosa, floor of mouth, lateral or ventral tongue, anterior tonsillar pillars, or soft palate) in which both sites receive a minimum cumulative radiation dose of 55 Gy.
7. Patient able to voluntarily provide written informed consent to participate in the study.
8. Capable of understanding and complying with the protocol requirements.
9. Adult patients aged between 18 to 75 years old.
10. Eastern Cooperative Oncology Group (ECOG) Performance Status of less than or equal to 2.
11. Adequate organ and bone marrow function as defined by:
a. Absolute neutrophil count (ANC) greater than or equal to 1.0 × 10^9/L (1,000/mm^3).
b. Haemoglobin (Hgb) greater than or equal to 9.0 g/dL.
c. Platelets greater than or equal to 75 × 10^9/L (75,000/mm^3).
d. Bilirubin less than or equal to 1.5 x the upper limit of normal (ULN).
e. Serum creatinine less than or equal to 1.5 x ULN or calculated creatinine clearance greater than or equal to 60 mL/min.
f. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 2.5 x ULN if no liver involvement, or less than or equal to 5 x ULN with liver involvement.
g. Albumin less than or equal to 3.5 g/dL or within normal range.
12. No evidence of any active oral mucositis (must be Grade 0 on WHO scale).
13. Ability to swish and swallow fluids in mouth without difficulty.
14. Able to minimise time in direct sunlight while on protocol.
15. Sexually active patients must agree to use medically-accepted barrier methods of contraception (e.g., male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 3 months after the last dose of study drug.
16. Women of childbearing potential (WCBP) must have a negative serum or urine pregnancy test at screening. WCBP includes any woman who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal.
17. Patient’s written informed consent to test for the human immunodeficiency virus (HIV).
Patient Exclusion Criteria
Patients who meet any of the following criteria will be excluded from the study:
1. Planned continuation of cisplatin or other chemotherapy following radiotherapy.
2. Patients with known infection of Human Immunodeficiency Virus (HIV) or have clinical signs and symptoms consistent with current HIV infection.
3. Known presence in serum of Hepatitis B surface antigen.
4. Evidence of any current active oral mucositis (must be Grade 0 on WHO scale).
5. Prior treatment including:
a. Radiotherapy or brachytherapy to the head and neck;
b. Cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) within 3 weeks, or nitrosoureas / mitomycin C within 6 weeks before the first dose of study treatment;
c. Treatment with therapeutic antibody less than 4 weeks before the first dose of study treatment;
d. Small molecule kinase inhibitor or other small molecule investigational agent within 14 days or 5 half-lives of the compound or active metabolites, whichever is greater, before the first dose of study treatment.
6. The patient has not recovered from toxicity due to all prior therapies (i.e., return to pre-therapy baseline or to Grade 0). Persistent > Grade 0 toxicity from prior therapy will be considered by the Sponsor for inclusion if there is no evidence of an overlapping ST-617 toxicity.
7. Major surgery within 21 days prior to first dose of study drug.
8. Current untreated or unresolved oral candidiasis or oral herpes simplex virus (HSV) infection.
9. History of thromboembolic or peripheral vascular disease (including Raynaud’s and systemic lupus erythematosus (SLE)).
10. Grade 2 or greater baseline neuropathy.
11. History of malabsorption or other gastrointestinal disease that may significantly alter the absorption of ST-617 (e.g., greater than or equal to Grade 2 nausea, vomiting or diarrhea).
12. History of poorly controlled Type 1 or Type 2 diabetes mellitus, with a haemoglobin A1c greater than or equal to 8%.
13. Uncontrolled significant intercurrent illness including, but not limited to, ongoing or active infection, history of congestive heart failure within 6 months, hypertension, unstable angina pectoris within 6 months, stroke within 6 months, myocardial infarction within 6 months, or cardiac arrhythmias. (Controlled chronic atrial fibrillation will not be excluded).
14. QTc interval corrected by Fridericia’s method greater than 450 msec for male patients or greater than 470 msec for female patients or history or risk factors for or use of medications known to prolong QTc interval or that may be associated with Torsades de Pointes (TdP) within 7 days of treatment start. CredibleMeds list of drugs known to cause TdP may be used as a reference for this study to determine which drugs are prohibited using the following link: https://crediblemeds.org/new-drug-list or a crediblemeds mobile application.
15. History of other medical or psychiatric illness or organ dysfunction which, in the opinion of the Investigator, would either compromise the patient’s safety or interfere with the evaluation of the safety of the study agent.
16. Concurrent administration of strong inhibitors of CYP3A4.
17. Concurrent administration of drugs that enhance photosensitivity.
18. The patient has a previously identified allergy or hypersensitivity to components of the study treatment formulation, dithiolethiones or platinum compounds.
19. Pregnant or breast-feedi
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method