None listed
Conditions
Brief summary
This is a Phase I, open-label study of the safety and biodistribution of two escalating doses of PEG-AVP0458, labeled with 3-5 mCi of 124I for PET imaging. This is the first study of PEG-AVP0458 in humans. PEG-AVP0458 is an experimental molecule, meaning that it is not approved for use in Australia or other parts of the world outside of this trial. The ultimate purpose of this research is to find better ways to detect and treat prostate and ovarian cancers. The product under investigation, PEG-AVP0458, has been designed to attach to a specific protein called TAG-72, which is found on the surface of some types of cancer cells however it is not a treatment for cancer. The aims of this study are to determine the safety of PEG-AVP0458 at the doses studied, and to demonstrate that PEG-AVP0458 can attach to the TAG-72 protein on prostate and ovarian cancer cells in humans. To enter the study patients with prostate or ovarian cancer need to screen as positive for TAG-72 and have disease deemed likely to be assessable by PET scan. An ECOG performance status of 0-1 and an expected survival of at least 3 months are also requirements for study entry. At screening participants must be of at least 18 years of age, provide informed consent to participate and show appropriate blood parameters. Patients with ovarian or prostate cancer are ineligible to participate if any of the exclusion criteria noted in the exclusion criteria section above. Trial Details PEG-AVP0458 will be combined with a low dose radioactive iodine particle by a process called radiolabelling, and injected. The radiolabel acts as a tracer, which means that it can be detected in tissue by a special scanning system called a PET scan. This study is designed to assess the safety and targeting ability of PEG-AVP0458, and no direct therapeutic benefit from the infusion of PEG-AVP0458 is anticipated. The first group of 3 participants enrolled will be allocated to the 1mg/m2 dose group. If any Dose Limiting Toxicities (DLTs) are seen for these 3 participants, the second group of 3 participants will also receive 1mg/m2. If no DLTs are seen in the first group of 3, the second group of 3 participants will receive the 10mg/m2 dose. If any DLTs are seen for these 3 participants, the third group of 3 participants will also receive 10mg/m2. If no DLTs are seen in the second group of 3, the third group of 3 participants (alongside a further 3 participants, total of 6) will receive either the 1mg/m2 or 10mg/m2 dose level, as determined by the outcome of the interim analysis.
Interventions
This is a Phase I, open-label study of the safety and biodistribution of two escalating doses of PEG-AVP0458, labelled with 3-5 mCi of 124I for PET imaging.
This is the first study of PEG-AVP0458 in humans. The ultimate purpose of this research is to find better ways to detect and treat prostate and ovarian cancers. The product under investigation, PEG-AVP0458, has been designed to attach to a specific protein called TAG-72, which is found on the surface of some types of cancer cells however
This is a Phase I, open-label study of the safety and biodistribution of two escalating doses of PEG-AVP0458, labelled with 3-5 mCi of 124I for PET imaging. This is the first study of PEG-AVP0458 in humans. The ultimate purpose of this research is to find better ways to detect and treat prostate and ovarian cancers. The product under investigation, PEG-AVP0458, has been designed to attach to a specific protein called TAG-72, which is found on the surface of some types of cancer cells however it is not a treatment for cancer. The aims of this study are to determine the safety of PEG-AVP0458 at the doses studied, and to demonstrate that PEG-AVP0458 can attach to the TAG-72 protein on prostate and ovarian cancer cells in humans. PEG-AVP0458 will be combined with a low dose radioactive iodine particle by a process called radiolabelling, and injected. The radiolabel acts as a tracer, which means that it can be detected in tissue by a special scanning system called a PET scan. 124I-PEG-AVP0458 is to be administered to patients by slow intravenous infusion over an hour, with safety monitoring during and for 4 hours post infusion. PET imaging will be performed post infusion of 124I-PEG-AVP0458 on Day 0, and on a further 4 occasions over a one week period. The first three patients entered into this study will receive 1 mg/m2 of PEG-AVP0458 (the first dose level). If no patients entered in the 1st dose group experience a dose-limiting toxicity (DLT) then the next dose group may commence 30 days after the last patient on the previous dose group has received the 124I-PEG-AVP0458 infusion. If any one patient experiences a DLT, then 3 additional patients will be entered in the 1 mg/m2 dose group. After completion of accrual into the first cohort (1 mg/m2 dose), a Trial Management Committee will review the safety data from these participants before a decision is made to escalate the dose to 10 mg/m2. The second dose group of three patients will receive 10 mg/m2 (second dose level), and the amount of 124I radioactivity is kept constant at 3-5 mCi. If any one patient experiences a DLT, then 3 additional patients will be entered in the 10 mg/m2 dose group. The last dose group of three patients will receive either 1 mg/m2 or 10 mg/m2. The dose will be determined by the Trial Management Committee following an interim analysis of safety data and the quality of imaging results obtained in the dose-escalation part of the study.
Sponsors
Avipep 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
Participants will be considered eligible for enrolment in the study if they meet all of the following criteria: Ovarian cancer -Patients with relapsed or refractory ovarian cancer -TAG-72-positive tumours -Detectable disease deemed likely to be assessable by PET by nuclear medicine physician as seen on imaging performed within 21 days of enrolling in the study -Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 -Expected survival of greater than or equal to 3 months -18 years of age or greater -Acceptable blood test results on screening (Platelet count greater than or equal to 100 x 109/L, absolute neutrophil count of greater than or equal to 1.5 x 109/L, Aspartate Aminotransferase (AST) less than or equal to 3x upper limit of normal (ULN), or less than 5x ULN with liver metastases,Total bilirubin less than or equal to 34 micro mol/L, Serum creatinine less than or equal to 160 micro mol/L) -Provision of written informed consent. Prostate cancer -Patients with prostate cancer -TAG-72-positive tumours -Detectable disease deemed likely to be assessable by PET by nuclear medicine physician as seen on imaging performed within 21 days of enrolling in the study -Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 -Expected survival of greater than or equal to 3 months -18 years of age or greater -Acceptable blood test results on screening (Platelet count greater than or equal to 100 x 109/L, Absolute neutrophil count greater than or equal to 1.5 x 109/L, AST less than or equal to 3x ULN, or less than 5x ULN with liver metastases,Total bilirubin less than or equal to 34 micro mol/L, Serum creatinine less than or equal to 160 micro mol/L) -Provision of written informed consent.
Exclusion criteria
Participants will not be entered in the study for any of the following reasons: Ovarian Cancer -Disease-specific exclusions -Evidence of current complete or partial bowel obstruction -Need for Intravenous or Total parenteral nutrition (TPN) hydration -Chemotherapy, immunotherapy, biologic therapy, radiation therapy, or other investigational product within 4 weeks prior to study entry or likely to be required during the 4-week on-study period -Patients using corticosteroids or immunosuppressive agents: low dose oral corticosteroids for concomitant medical conditions are permitted. Inhaled or topical corticosteroids are permitted. -Patients with active infections requiring antibiotics, with bleeding disorders or with other serious illness -Women who are pregnant (positive hCG test) or lactating -Women of child-bearing potential who are unwilling to utilize a medically acceptable method of contraception -Patients with a concurrent active serious medical condition likely to affect participation in the study, such as a documented myocardial infarction less than or equal to 3 months prior to screening or unstable angina pectoris. -Patients unable to sign informed consent or unwilling to comply with the procedural requirements of this clinical protocol. Prostate cancer -Chemotherapy (not including androgen deprivation therapy), immunotherapy, biologic therapy, radiation therapy, or other investigational product within 4 weeks prior to study entry or likely to be required during the 4-week on-study period -Patients using corticosteroids or immunosuppressive agents: low dose oral corticosteroids for concomitant medical conditions are permitted. Inhaled or topical corticosteroids are permitted. -Patients with active infections requiring antibiotics, with bleeding disorders or with other serious illness -Patients with a concurrent active serious medical condition likely to affect participation in the study, such as a documented myocardial infarction less than or equal to 3 months prior or to screening or unstable angina pectoris -Men who are unwilling to utilize a medically acceptable method of contraception -Patients unable to sign informed consent or unwilling to comply with the procedural requirements of this clinical protocol.
Outcome results
None listed