None listed
Conditions
Brief summary
This study will be conducted in two parts to assess the safety of AT-0174, how the treatment interacts within the body and to determine the maximum safe dose that may be administered to patients with advanced solid cancers. Who is it for? You may be eligible for this study if you are aged 18 years or older and you have been diagnosed with a solid cancer, including but not limited to: non-small cell lung carcinoma, small cell lung carcinoma, triple-negative breast carcinoma, malignant melanoma, gastric carcinoma/gastroesophageal junction carcinoma/oesophageal cancer, colorectal carcinoma, pancreatic ductal adenocarcinoma, epithelial ovarian carcinoma (fallopian, ovarian, primary peritoneal carcinoma), endometrial carcinoma, thyroid carcinoma (non- medullary) or moderate-high grade astrocytoma (brain cancer). Study details This study will be conducted across two parts. In the first sub-study (Part 1), participants who choose to enrol in this study will be allocated to the next available dosing cohort. The first cohort will be asked to take a daily oral capsule of AT-0174 for 7 days, followed by 3 weeks of no treatment. The second cohort will be asked to take a daily oral capsule of AT-0174 for 14 days, followed of 2 weeks of no treatment. The third cohort will be asked to take a daily oral capsule of AT-0174 for 28 days with no breaks. In the second sub-study (Part 2), participants who choose to enrol in this study will be allocated to the next available dosing cohort. This sub-study will ask all participants to take a daily oral capsule of AT-0174 for 28 days with no breaks. The dose of AT-0174 may increase in amount or frequency (e.g., twice per day) with each successive cohort in Part 2, based on a careful assessment of the safety and tolerability of each dose. All participants will have their vital signs (heart rate, blood pressure, temperature, etc) checked and will provide blood and urine samples for testing. In addition, participants will have their cancer assessed using CT, MRI or CT/PET scans during the study. Participants may continue taking AT-0174 for as long as they and their doctor agree. It is hoped this research will determine the maximum dose of AT-0174 that can be administered safely without causing severe reactions. Once the safest maximum dose of AT-0174 has been determined, a larger trial investigating the efficacy of AT-0174 as a treatment for a greater number of cancer patients may proceed.
Interventions
Treatment cycles will be 28 days in duration and may continue as long as the participant agrees and is tolerating treatment, and if there is potential clinical benefit as determined by the Investigator. Each cohort will be assessed for dose-limiting toxicities during the first 28 days before enrolment commences in the next cohort. Separate participants will be enrolled into each cohort but may escalate to the next dosing duration or level if it is found to be safe and at Investigator's discretio
Treatment cycles will be 28 days in duration and may continue as long as the participant agrees and is tolerating treatment, and if there is potential clinical benefit as determined by the Investigator. Each cohort will be assessed for dose-limiting toxicities during the first 28 days before enrolment commences in the next cohort. Separate participants will be enrolled into each cohort but may escalate to the next dosing duration or level if it is found to be safe and at Investigator's discretion. Treatment adherence will be assessed using daily dosing diaries and the return of unused capsules after each cycle. In Part 1, AT-0174 will be administered orally, once daily at a dose of 50 mg once daily for 7 days followed by a 21-day safety observation or follow-up period (Cohort 1). The duration of AT-0174 (50 mg) treatment will then be prolonged to 14 consecutive days (Cohort 2) and then 28 consecutive days (Cohort 3) in each 28-day cycle. In Part 2, AT-0174 will be administered once daily as an oral capsule for 28 consecutive days of each 28-day cycle. The dose level will be escalated across up to 3 cohorts in Part 2, with the exact dose in each cohort to be selected based on the safety and tolerability of AT-0174 in previous cohorts. Enrolment into Part 2 will commence following the safety review of Cohort 3 data.
Sponsors
Antido Therapeutics (Australia) Pty Ltd
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
- Able to understand, sign, and commit to informed consent and to all study procedures - Histological/cytological evidence of one of the following unresectable locally advanced or metastatic solid cancers: a. Non-small cell lung carcinoma b. Small cell lung carcinoma c. Triple-negative breast carcinoma d. Malignant melanoma e. Gastric carcinoma/gastroesophageal junction carcinoma/esophageal adenocarcinoma f. Squamous cell carcinoma of the esophagus g. Colorectal carcinoma h. Pancreatic ductal adenocarcinoma i. Epithelial ovarian carcinoma (fallopian, ovarian, primary peritoneal carcinoma) j. Endometrial carcinoma k. Thyroid carcinoma (non-medullary) l. Moderate-high grade astrocytoma (oligodendroglioma, astrocytoma, or anaplastic astrocytoma [Grade 2 or 3] and glioblastoma multiforme [Grade 4]) m. Other cancers based on the Investigator’s discretion with Sponsor Medical Monitor’s approval. - Locally advanced unresectable or metastatic disease that is refractory to standard therapy, or for whom no standard therapy exists, and where standard therapy is contraindicated or has been declined by the patient - Measurable or evaluable disease per RECIST v1.1, or Grades 2-4 astrocytoma as per RANO-HGG or RANO-LGG criteria, that was not in a prior radiation or other locally treated area unless imaging-based progression has been clearly documented following radiation or other local therapy - Eastern Cooperative Oncology (ECOG) performance status less than or equal to 1 - Life expectancy greater than or equal to 3 months - Adhere to contraception requirements where applicable
Exclusion criteria
- Prior radiotherapy within two weeks of treatment - Treatment with anticancer therapies including cytotoxic chemotherapy, monoclonal antibodies (mAbs), and/or small molecule tyrosine kinase inhibitors within 14 days prior to study therapy administration, or 5 half-lives, whichever is shorter (42 days for prior nitrosourea or mitomycin-C) - Major surgery within 28 days of the Screening visit - Therapeutic radiopharmaceuticals within 8 weeks of treatment - Systemic treatment with either corticosteroids (> 10 mg/day prednisone or equivalent) or other immunosuppressive medications within 14 days before the planned first dose of study drug - Clinically significant gastrointestinal disorder that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels - Evidence or history of uncontrolled, clinically significant haematological, renal, hepatic, endocrine, pulmonary, gastrointestinal, cardiovascular, psychiatric, coagulation neurologic, dermatologic, autoimmune, or allergic disease - Additional active malignancy that is progressing or has required active treatment within the past 3 years - Known active CNS metastases and/or carcinomatous meningitis
Outcome results
None listed