None listed
Conditions
Brief summary
This is an open-label multiple ascending dose study to assess the safety and tolerability of PMR-116, a drug treatment for patients with advanced solid tumours of any cancer type. Who is it for? You may be eligible for this study if you are aged 18 years or older, have been diagnosed with a solid tumour of any cancer type, and you have previously failed treatment with other available therapies indicated for your cancer (including chemotherapy, surgery and radiation therapy). Study details This trial will be conducted across two parts. In the first study part (Dose escalation), up to six participants will receive multiple doses of PMR-116, to be taken at set times throughout a 28-day treatment cycle. All participants will have their vital signs checked (heart rate, blood pressure, temperature, etc), and will provide blood and urine samples for testing. If the drug appears safe, additional participants in a second cohort will receive an increased dose of PMR-116 to be taken at set times throughout a 28-day treatment cycle. Up to 5 increasing doses will be investigated in separate treatment cohorts until the maximum safe dose has been determined. Following Dose Escalation will be Dose Schedule Optimization. Dose Schedule Optimisation will also assess the safety and tolerability of PMR-116 and identify the maximum feasible dose and the dose administration schedule. All participants will undergo the same assessments as listed in the Dose Escalation portion of the study, however 3 dosing schedules of 2-days dosing/5-days off; 3-days dosing/4-days off & 4-days dosing/10-days off will be explored. Dose levels explored will not exceed 1800mg/week. Participants enrolled in the Dose Expansion and Dose Schedule Optimization phases of the study will be asked to provide a sample of their archival tumour before commencing PMR-116 treatment., In the second study part (Dose expansion), a new cohort of participants will receive multiple doses of the maximum safe dose of PMR-116 to be taken at set times throughout a 28-day treatment cycle. All participants will have their vital signs checked and will provide blood and urine samples for testing. Participants enrolled in the dose expansion study will also be asked to provide a sample of their tumour (taken by a biopsy) before starting and again 22 days after starting PMR-116 treatment, It is hoped this research will determine the maximum dose of PMR-116 that can be administered safely without causing severe reactions. Once the dose of PMR-116 has been determined, a larger trial investigating the efficacy of PMR-116 as a treatment for cancer patients with advanced solid tumours may pr
Interventions
PMR-116 will be administered as an oral liquid contained within a pre-filed syringe at the dose defined by the protocol and the SRC. Participants will fast 2 hours prior to and 1 hour post each dose.
Part 1:
Dose Escalation - multiple ascending dose cohorts
PMR-116: will be self administered by the participant once every 7 days, with each cycle being 28 days. PMR-116 will be given at either 300mg, 600mg, 900mg, 1350mg and 1800mg per dose.
In this dose escalation phase individual dosing coh
PMR-116 will be administered as an oral liquid contained within a pre-filed syringe at the dose defined by the protocol and the SRC. Participants will fast 2 hours prior to and 1 hour post each dose. Part 1: Dose Escalation - multiple ascending dose cohorts PMR-116: will be self administered by the participant once every 7 days, with each cycle being 28 days. PMR-116 will be given at either 300mg, 600mg, 900mg, 1350mg and 1800mg per dose. In this dose escalation phase individual dosing cohorts will be sequentially enrolled. The decision to escalate to the next dose level in this phase of the study will be made following evaluation of the safety, efficacy and pharmacodynamic data by the Safety Review Committee (SRC). Dose Schedule Optimization – multiple dose levels with dose administration of 2-, 3- or 4-consecutive days Following completion of the dose escalation phase, further optimization of the dose administration schedule with PMR-116 will be conducted. Oral PMR-116 will be administered with dosing schedules of 2days on/5 days off, 3 days on/4 days off or 4-days on/10 days off, with each cycle being 28 days. The first two cohorts will be concurrently enrolled, at 400mg, 3 days on/5 days off and 600mg, 2 days/4 days off. Participants will be enrolled on a 1:1 basis between the two dosing regimens. Following these two cohorts, the dose and the dosing schedule for future cohorts will be determined by the SRC following evaluation of the safety, efficacy and pharmacodynamic data. The total weekly dose level not exceed 1800mg/week. Part 2: Dose Expansion – single dose cohort Oral PMR-116 will be self administered at a dose and dose schedule determined by the SRC following the dose escalation and dose schedule optimisation phases of the study. In all parts of the study, participants will be required to capture their dosing in a participant diary that will be reviewed by the clinical unit staff at scheduled site clinic visits and to return to the site their used dosing syringes. Participants will continue to receive study drug until they are no longer considered to be achieving clinical benefit; they have unacceptable toxicity; or they withdraw informed consent. Study participation consists of 28 day screening period, treatment period and an a End of Treatment visit will be conducted 30 days after the last dose of PMR-116. Attendance at the clinical unit will be dependent on the dosing schedule enrolled in, as described below: • Dose Escalation, dosing every 7 days: . Cycle 1 Days 1, 2,8,15,22 and 23, Cycle 2 Days 1 and 15, and Day 1 of each subsequent cycle • Dose Schedule Optimization, 2 days on/5 days off: Cycle 1 days 1, 2, 3, 8, 9, 15, 22, 23, 24, Cycle 2 days 1, 2, 15 and Day 1 of subsequent cycles. • Dose Schedule Optimization, 3 days on/4 days off: Cycle 1 days 1, 2, 3, 4, 8, 9, 10, 15, 22, 23, 24, 25. Cycle 2 days 1, 2, 3, 15, 16 and Day 1 of subsequent cycles. • Dose Schedule Optimization, 4 days on/10 days off: Cycle 1 days 1, 2, 3, 4, 5, 15, 16, 17, 18, 19. Cycle 2 days 1, 15 and Day 1 of subsequent cycles. Participants may only take part in either the Dose Escalation, Dose Schedule Optimization or the Dose Expansion aspects of the study and, where enrolled into the Part 1-Dose Escalation / Dose Schedule Optimization phases, only one cohort.
Sponsors
Pimera 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
• Ability to understand and be willing to sign an informed consent form. • MYC positive, histopathologically confirmed, locally advanced or metastatic cancer (solid tumour) for which all available standard of care treatment options has been exhausted or refused and for which at least one lesion is measurable. • Most recent chemotherapy treatment at least 3 weeks, or monoclonal antibody treatment at least 4 weeks, or allogeneic stem cell transplantation at least 24 weeks or radiation therapy at least 3 weeks prior to starting treatment with PMR-116. • Males and females aged over 18 years • Eastern Cooperative Oncology Group (ECOG) status of 0 to 1 • Adequate liver and renal function as evidenced by pathology test results • No recent major surgery at least 4 weeks prior to starting treatment with PMR-116 • Females must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal. • Males must be surgically sterile, abstinent, or if engaged in sexual relations with a woman of child-bearing potential, the participant and his partner must be surgically sterile or using an acceptable, highly effective contraceptive method from screening until study completion. • Be willing to use protective measures against sun exposure and avoid the use of tanning salons and tanning beds • Have an estimated life expectancy of at least 3 months. • Dose Expansion only: Have a site of disease amenable to biopsy and be willing to undergo a biopsy prior to and during treatment with PMR-116
Exclusion criteria
• Receiving any concurrent anti-cancer therapy • Adverse Events from prior treatments which have not recovered to at least a mild (Grade 1) severity • Symptomatic primary Central Nervous System (CNS) cancer or metastases unless the symptoms are stable with no CNS surgery or radiotherapy within 28 days prior to the first dose of PMR-116 • Any uncontrolled illness that would limit compliance with study requirements • Any uncontrolled infection • Known Human Immunodeficiency Virus (HIV) infection • Active hepatitis B or hepatitis C infection • Pregnant or breast feeding • Unable to swallow oral medications • Gastrointestinal conditions that could affect absorption of PMR-116 • Evidence of abnormal cardiac function • Prior treatment with an RNA polymerase I inhibitor
Outcome results
None listed