None listed
Conditions
Brief summary
This purpose of this study is to determine the safety, tolerability and efficacy of MG010 in combination with sorafenib in patients with solid tumors who have failed existing treatments Who is it for? You may be eligible to join this study if you are aged between 18 years and above, and have histologically confirmed diagnosis of advanced or metastatic solid tumors for which standard treatment is unavailable/ineffective/intolerable Study details All participants in this study will receive MG010 and sorafenib. This study will have 2 stages: the dose escalation stage and the dose expansion stage. In the dose escalation stage, there will be 3 groups of participants who each receive different doses of each drug. The drug will be given orally once every day of a 28-day cycle. In the dose expansion stage, participants will receive once/twice a day MG010 and once daily sorafenib (at a dose determined from the dose escalation stage) for up to 6 28-day cycles. Participants will be monitored for reactions and treatment effectiveness, and provide blood and urine for analysis. Medical imaging, e.g. PET and/or CAT scans for stage I will be performed at the beginning and the end. For stage II 5 images will be taken throughout the study; at screening, days, 56, 112, 168 and 210. It is hoped this trial will provide information on the treatment of solid tumours by demonstrating a benefit in the proposed combination treatment, by improving the tolerability and expand the usage of sorafenib in cancer treatment.
Interventions
Stage 1 of the trial - dose escalation
Cohort 1: 200mg tablet Sorafenib once daily and 200 mg capsule MG010 once daily for up to one cycle (28 days)
Cohort 2: 200mg tablet Sorafenib once daily and 400 mg capsules MG010 once daily for one cycle (28 days)
Cohort -1: 200mg tablet Sorafenib once daily and 100 mg capsule MG010 once daily for one cycle (28 days)
Cohort and Phase Timing:
Cohort 1 concludes when all subjects complete their cycles, then safety assessments are undertaken within 7 days of
Stage 1 of the trial - dose escalation Cohort 1: 200mg tablet Sorafenib once daily and 200 mg capsule MG010 once daily for up to one cycle (28 days) Cohort 2: 200mg tablet Sorafenib once daily and 400 mg capsules MG010 once daily for one cycle (28 days) Cohort -1: 200mg tablet Sorafenib once daily and 100 mg capsule MG010 once daily for one cycle (28 days) Cohort and Phase Timing: Cohort 1 concludes when all subjects complete their cycles, then safety assessments are undertaken within 7 days of the last patients. If Dose Limiting Toxicity (DLT) is observed in >1 out of 6 subjects in cohort 1, 3 subjects will be recruited for dose cohort -1 (dose de-escalation); Cohort 2 commences with 3 new patients and after all subjects complete their cycles, then within 7 days safety assessments are performed. After approximately 2 weeks, if all goes well, the report of the safety committee will be finalised, after which stage 2 will commence if the report provides a favourable recommendation. Stage 1 participants are eligible for stage 2, subject to signing a new informed consent and compliance with the inclusion exclusion criteria. Stage 2 of the trial - dose expansion stage The dose will be decided at the completion of stage 1. Sorafenib once daily and MG010 once or twice daily for up to six cycles (168 days) Adherence will be monitored by returned medication counts.
Sponsors
Metagone Biotech Australia Pty Ltd
Study design
Allocation
Non-randomised trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1.Age over 18 years 2.For subject to be enrolled in cohort 1 of dose-escalation stage: Histologically confirmed diagnosis of advanced or metastatic solid tumors for which standard treatment is unavailable/ineffective/intolerable. 3. For subject to be enrolled in additional cohorts of dose- escalation stage and dose expansion cohort: Histologically confirmed diagnosis of one of the following advanced or metastatic solid tumours for which standard treatment is unavailable/ineffective/intolerable: a.Non-small cell lung carcinoma b.Renal cell carcinoma c.Colorectal cancer, or d. Hepatocellular carcinoma with liver function of Child-Pugh Class A or B (score 7 only), who are resistant to sorafenib 4.Disease progression within 6 months after most recent standard therapy 5.ECOG performance status of less than or equal to 2 6.Have at least one tumour lesion measurable in a unidimensional way with either spiral CT/PET or CT or MRI (in case of brain lesions) only according to Response Evaluation Criteria In Solid Tumours (RECIST 1.1) 7.Adequate organ function within 14 days prior to enrolment, as defined below: a.Bilirubin less than or equal to x Upper Normal Limit (UNL) b.AST/ALT/ALP < 5 x UNL c.Polynuclear neutrophils greater than or equal to 1 500/mm^3 d.Haemoglobin > 90g/L e.Platelets greater than or equal to 100 000/mm^3 f.Serum Creatinine < 2 x UNL g.GFR > 30 mL/min 8. .Adequate oral intake without the need for enteral or parenteral feeding 9.Life expectancy > 3 months 10.Ability to understand and willing to sign a written informed consent document and to comply with the study protocol 11.Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry, during the last study period and for the following 6 months after the last study drug intake. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately 12.No known or suspected allergy or hypersensitivity to sorafenib or any component of the excipients of MG010 13.For subjects with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated 14. Subjects with a history of hepatitis C virus (HCV) infection must have been treated and cured. For subjects with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
Exclusion criteria
1.Surgery (except biopsy) within 4 weeks before enrolment 2.Received any chemotherapy, radiotherapy, targeted therapy or immunotherapy within 4 weeks prior to the enrolment 3.Archived tumour tissue, biopsy tissue or blood sample not available/not suitable for analysis of pDAPKS308 expression 4.History of additional malignancies, except non-melanoma skin cancer, in situ cancer of the cervix, or other solid tumours thathave been considered cured for > 3 years 5.Participated in any other investigational trial, unless treatment in that trial has been discontinued at least 30 days prior to the enrolment 6.Known or suspected allergy or hypersensitivity to any of the therapeutic agents to be administered during the study 7.Uncontrolled concurrent illness including, but not limited to active infection, symptomatic congestive heart failure or cardiac arrhythmia 8.Known to have hypertension (systolic BP>180mmHg or diastolic BP>110mmHg) 9.Receiving inducers of CYP3A4 activity (for example, St. John’s wort, phenytoin, carbamazepine, phenobarbital, and dexamethasone) or sensitive substrates of CYP1A2, 1B1, 2C8, and 2C19 (e.g. theophylline, duloxetine, alosetron or tizanidine) within 2 weeks prior to the enrolment 10.Uncontrolled mental disease or psychotic manifestation that would prohibit compliance with the protocol, the understanding of the informed consent form or the ability to withdraw from the study 11.Malabsorption problem that may affect absorption of sorafenib or MG010 12.ActiveHIV, HBV or HCV infections 13.Pregnancy or breast feeding
Outcome results
None listed