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Trial registered on ANZCTR


Registration number
ACTRN12620000541909
Ethics application status
Approved
Date submitted
9/09/2019
Date registered
4/05/2020
Date last updated
4/05/2020
Date data sharing statement initially provided
4/05/2020
Type of registration
Retrospectively registered

Titles & IDs
Public title
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
Scientific title
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
Secondary ID [1] 300736 0
N/A
Universal Trial Number (UTN)
Trial acronym
Linked study record
Registration number for the Phase 2 study is: ACTRN12620000540910

Health condition
Health condition(s) or problem(s) studied:
Oral Mucositis 313426 0
Head and Neck Cancer 316548 0
Condition category
Condition code
Cancer 311861 311861 0 0
Head and neck
Oral and Gastrointestinal 312906 312906 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This Phase 1b part of the study will be an open-label, dose-finding study to:

• Test the safety and tolerability of ST-617 (to find out what effects ST-617 has, at different doses) on patients and their oral cavities while they are being treated with chemoradiation for head and neck cancer.

• Find the highest dose of ST-617 that can be given without causing bad side-effects (and that will be used in the Phase 2 part of the study).

• Find out other things about ST-617 such as:
- what the body does to ST-617 after swallowing it
- what ST-617 does to certain molecules and genes in the body
- how soon severe oral mucositis (OM) starts in patients receiving chemoradiation
- how bad OM becomes and how long it lasts, with and without the treatment of ST-617

Participants will receive either best supportive care (BSC) alone, or BSC plus an oral suspension of ST-617 administered daily for 3 days prior to the start of radiation, and then daily during radiation treatment. Radiation treatment duration will last for up to approximately 6 to 8 weeks, however this duration will vary among participants and will depend on clinician's discretion.

Initially, a minimum of 3 evaluable patients will receive an oral suspension of ST-617 at the 50 mg dose level plus BSC daily during chemoradiation treatment. After the third patient at the 50 mg dose completes 21 days of oral suspension of ST-617, the Safety Review Committee will review the safety data for the 3 patients and will decide to either expand the number of patients at the dose level or escalate to the next dose (or an intermediary dose level).

The 'safe' dose will be determined by medical monitors evaluating a minimum of two dose levels of ST-617 to determine the recommended Phase 2 dose (RP2D) of ST-617 for the attenuation of OM.

BSC is defined as a specific oral hygiene regimen based on current guidelines, and practices to minimise the risk of mucosal injury and reduce the risk of secondary oral infection. To assure compliance each patient will be provided with a kit containing supplies necessary for BSC and instructions regarding its use. During the study, patients will be given a kit that has been specifically designed for patients at risk of radiation induced dental disease. This kit contains a toothbrush, toothpaste, dental floss, fluoride gel, oral rinse, and chewing gum. Patients will also receive instructions on how best to use these items to lower the amounts of bacteria on teeth and gums and make teeth more resistant to tooth decay.

Radiation treatment duration will last for up to approximately 6 to 8 weeks, however this duration will vary among participants and will depend on clinician's discretion.

The dose levels are currently planned to be 50 mg and 100 mg, however, after pharmacokinetic (PK) and safety data are reviewed from each cohort, other doses within the dose range of 50 mg to 150 mg may be evaluated with a minimum of 6 patients enrolled in each dose cohort evaluated. Although patients will be treated with ST-617 for the duration of their chemoradiation therapy, the decision to dose escalate to a new cohort will be based on safety monitoring, occurrence of drug-related toxicities throughout the first 21 days of ST-617 treatment and clinician's discretion.

Doses will be provided as one 50 mg dose suspended in one 15 mL bottle.

Accountability for the study drug at the study site is the responsibility of the Investigator. The Investigator will ensure that the study drug is used only in accordance with the study protocol. The Investigator may assign the drug accountability responsibilities to a pharmacist or other appropriately trained individual; however, the Investigator remains ultimately responsible for drug accountability.

Drug accountability records indicating the drug’s delivery date to the site, inventory at the site and use/dispensing will be maintained. These records will adequately document that study drugs were used and dispensed as specified in the study protocol.

Accountability records will include dates, quantities, batch/lot numbers, number of vials, and patient numbers. The Sponsor (or its designee) will review drug accountability records at the site on an ongoing basis during the study. All unused supplies must be inventoried, accounted for, and returned to Sponsor (or its designee), or if authorised, disposed of at the study site. Records of disposal must be maintained with the study records.

To ensure compliance each patient will be provided with a kit containing supplies necessary for BSC and instructions regarding their use.
Intervention code [1] 314846 0
Treatment: Drugs
Comparator / control treatment
There will be no comparator/control treatment in Phase 1b part of this study,
Control group
Uncontrolled

Outcomes
Primary outcome [1] 320532 0
Phase 1b part of the study

Duration of, equal to or greater than, Grade 3 oral mucositis as determined by the World Health Organisation (WHO) oral mucositis assessment scale.

Incidence of oral mucositis will be assessed by trained assessors using a structured template developed by Primary Endpoint Solutions(PES). Data collection will be standardised, and oral mucositis scores will be centrally assigned by PES to the WHO, National Cancer Institute (NCI) and Radiation Therapy Oncology Group (RTOG) scales based on the information provided.
Timepoint [1] 320532 0
Oral mucositis assessments will be done at Screening, before each weekly treatment on Day 1, and then twice weekly with at least 48 hours between assessments, and then once weekly (if necessary) after cessation of radiation therapy until oral mucositis resolves to less than or equal to Grade 1 or until start of new treatment. Oral mucositis will also be assessed at the End of Treatment Visit and the 30-Day Safety Follow-Up Visit.

The End of Treatment visit will be assessed on the last day of the last week that participants receive radiation therapy. Participants will be asked to come to the clinic for approximately 1-2 hours to complete the required tests (e.g. heart rate, blood pressure, breathing rate and body temperature) and answer straight forward questions (e.g. whether any adverse events were experienced).
Secondary outcome [1] 371936 0
Phase 1b part of the study

Incidence of severe (WHO Grade 3 or 4) oral mucositis during the active treatment period.

Incidence of oral mucositis will be assessed by trained assessors using a structured template developed by PES. Data collection will be standardised, and oral mucositis scores will be centrally assigned by PES to the WHO, NCI and RTOG scales based on the information provided.
Timepoint [1] 371936 0
Oral mucositis assessments will be done at Screening, before each weekly treatment on Day 1, and then twice weekly with at least 48 hours between assessments, and then once weekly (if necessary) after cessation of radiation therapy until oral mucositis resolves to less than or equal to Grade 1 or until start of new treatment. Oral mucositis will also be assessed at the End of Treatment Visit and the 30-Day Safety Follow-Up Visit.

The End of Treatment visit will be assessed on the last day of the last week that participants receive radiation therapy. Participants will be asked to come to the clinic for approximately 1-2 hours to complete the required tests (e.g. heart rate, blood pressure, breathing rate and body temperature) and answer straight forward questions (e.g. whether any adverse events were experienced).
Secondary outcome [2] 375188 0
Phase 1b part of the study

Time to onset of severe oral mucositis.

Incidence of oral mucositis will be assessed by trained assessors using a structured template developed by PES. Data collection will be standardised, and oral mucositis scores will be centrally assigned by PES to the WHO, NCI and RTOG scales based on the information provided.
Timepoint [2] 375188 0
Oral mucositis assessments will be done at Screening, before each weekly treatment on Day 1, and then twice weekly with at least 48 hours between assessments, and then once weekly (if necessary) after cessation of radiation therapy until oral mucositis resolves to less than or equal to Grade 1 or until start of new treatment. Oral mucositis will also be assessed at the End of Treatment Visit and the 30-Day Safety Follow-Up Visit.

The End of Treatment visit will be assessed on the last day of the last week that participants receive radiation therapy. Participants will be asked to come to the clinic for approximately 1-2 hours to complete the required tests (e.g. heart rate, blood pressure, breathing rate and body temperature) and answer straight forward questions (e.g. whether any adverse events were experienced).
Secondary outcome [3] 375425 0
Phase 1b part of the study

Change in patient-reported mucositis-related mouth pain.

The Oral Mucositis Daily Questionnaire (OMQD), developed by PES, will be used by participants to assess patient-reported mouth pain.
Timepoint [3] 375425 0
Participants will be asked to complete the OMQD at the start of the first dose of the study drug (3 days prior to the initiation of radiation), and then daily through to the 30-Day Safety Follow-Up Visit.

This questionnaire will be used by participants to assess a change in patient-reported mouth pain.
Secondary outcome [4] 380852 0
Phase 1b part of the study

Change in analgesic use.

The OMQD, developed by PES, will be used by participants to assess change in analgesic use.

The change in analgesic use will also be assessed by clinicians that employ assessment scales developed by the WHO, NCI and RTOG.
Timepoint [4] 380852 0
Participants will be asked to complete the OMQD at the start of the first dose of the study drug (3 days prior to the initiation of radiation), and then daily through to the 30-Day Safety Follow-Up Visit.

This questionnaire will be used by participants to assess a change in analgesic use.

Eligibility
Key inclusion criteria
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).
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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-feeding women.

20. Unable to eat a solid diet due to sequelae of surgery or tumor, or gastrostomy-feeding dependence at baseline.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
12/11/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
134
Accrual to date
12
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 14092 0
The Chris O’Brien Lifehouse - Camperdown
Recruitment hospital [2] 14093 0
Liverpool Hospital - Liverpool
Recruitment hospital [3] 14094 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [4] 14095 0
Barwon Health - McKellar Centre campus - North Geelong
Recruitment hospital [5] 14096 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 26882 0
2050 - Camperdown
Recruitment postcode(s) [2] 26883 0
2170 - Liverpool
Recruitment postcode(s) [3] 26884 0
5042 - Bedford Park
Recruitment postcode(s) [4] 26885 0
3215 - North Geelong
Recruitment postcode(s) [5] 26886 0
5000 - Adelaide
Recruitment outside Australia
Country [1] 21754 0
South Africa
State/province [1] 21754 0

Funding & Sponsors
Funding source category [1] 303127 0
Commercial sector/Industry
Name [1] 303127 0
Supportive Therapeutics LLC
Country [1] 303127 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
PSI CRO Australia Pty. Ltd.
Address
Suite 2.01, 16 Giffnock Avenue, Macquarie Park, NSW 2113
Country
Australia
Secondary sponsor category [1] 303124 0
Commercial sector/Industry
Name [1] 303124 0
Supportive Therapeutics LLC
Address [1] 303124 0
One Broadway, 14th Floor, Cambridge, MA 02142
Country [1] 303124 0
United States of America

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303676 0
Central Adelaide Local Health Network Human Research Ethics Committee
Ethics committee address [1] 303676 0
Level 3, Roma Mitchell House, 136 North Terrace, Adelaide, South Australia, 5000
Ethics committee country [1] 303676 0
Australia
Date submitted for ethics approval [1] 303676 0
Approval date [1] 303676 0
10/04/2019
Ethics approval number [1] 303676 0
Ethics committee name [2] 305707 0
Southern Adelaide Clinical Human Research Ethics Committee
Ethics committee address [2] 305707 0
Flinders Medical Centre
Ward 6C
Room 6A219
Flinders Drive
Bedford Park SA 5042
Ethics committee country [2] 305707 0
Australia
Date submitted for ethics approval [2] 305707 0
23/11/2018
Approval date [2] 305707 0
07/05/2019
Ethics approval number [2] 305707 0
HREC/18/SAC/413

Summary
Brief summary
Introduction
As you are going to be treated with chemoradiation therapy for your head and neck cancer, you will most likely develop oral mucositis. As such this study is testing an experimental treatment for oral mucositis. This experimental treatment is called ST-617.
Oral mucositis involves painful ulcers or lesions developing in the lining of your mouth. There are currently no approved medicines to successfully prevent and/or treat oral mucositis for head and neck cancer patients. Most patients are treated with best supportive care (BSC) which includes such things as making sure you are taking care of your mouth properly, providing ice chips or lozenges to suck on, or swishing with a mouthwash.
This study aims to test the safety and tolerability of ST-617 on patients and their oral cavities while they are being treated with chemoradiation for head and neck cancer. There are two arms to this study, Phase 1b and Phase 2. It is hoped that the Phase 1 arm will help determine the recommended dose of ST-617 that will be used in head and neck cancer patients in the Phase 2 study.
ST-617 is a medication that has been widely studied in multiple human clinical trials and belongs to a group of medications that have been shown to help protect cells from damage.
Who is it for?
You may be eligible for this study if you are an adult who has been diagnosed with head and neck cancer who is planning to undergo chemoradiation.
Study details
In the Phase 1b part of the study participants will receive either Best Supportive Care (BSC) alone, or BSC plus an oral suspension of ST-617 administered daily for 3 days prior to the start of radiation, and then daily during radiation treatment.
Participants will attend hospital visits for approximately 4 months. After the last visit, their study doctor will check on the status of their cancer every 3 months for up to 1 year after they started radiation.
Most of the exams, tests, and procedures that will be done during this study are part of regular medical care, but will be done multiple times so more information can be gathered.
Participation in this study will be divided into different visits: Screening Period, Treatment Period, End of Treatment, 30-Day Safety Follow-Up and Response Follow-Up Visits.
Blood will be taken from a vein in the participants’ arm for testing of their general health and to check their medical condition.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 94458 0
Dr Hien Le
Address 94458 0
Department of Radiation Oncology, Royal Adelaide Hospital, Port Road, Adelaide, South Australia, 5000
Country 94458 0
Australia
Phone 94458 0
+61 8 8222 4391
Fax 94458 0
Email 94458 0
[email protected]
Contact person for public queries
Name 94459 0
Justine Lee
Address 94459 0
PSI CRO Australia Pty. Ltd.
Suite 2.01, 16 Giffnock Avenue, Macquarie Park, New South Wales, 2113.
Country 94459 0
Australia
Phone 94459 0
+61 2 8582 1672
Fax 94459 0
Email 94459 0
[email protected]
Contact person for scientific queries
Name 94460 0
Justine Lee
Address 94460 0
PSI CRO Australia Pty. Ltd.
Suite 2.01, 16 Giffnock Avenue, Macquarie Park, New South Wales, 2113.
Country 94460 0
Australia
Phone 94460 0
+61 2 8582 1672
Fax 94460 0
Email 94460 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
IPD will not be shared due to patient confidentiality and privacy.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.