Phase I Safety and Biodistribution Study of 124I-PEG-AVP0458 Diabody in Patients with TAG-72 Positive Ovarian and Prostate Cancer
- Conditions
- Ovarian cancerProstate cancerCancer - Ovarian and primary peritonealCancer - Prostate
- Registration Number
- ACTRN12612000802808
- Lead Sponsor
- Avipep Pty Ltd
- Brief Summary
See attached abstract. The engineered antibody PEG-AVP0458 (a diabody) had proven to be most effective in loading extremely high levels of radioactive payloads into human tumours grown in mice (known as xenografts). This clinical study was a first-in-man test to determine whether the Antibody PEG-AVP0458 also uploaded diagnostic payloads into cancer metastases. Six patients were recruited into the study (age range 62-85yrs) one with relapsed ovarian cancer and five with recurrent metastatic prostate cancer. The antibody PEG-AVP0458 was first radiolabelled with 124-Iodine, a positron emitter detectable by PET-cameras, and injected intravenously. The patients were scanned by PET camera at 0,1,2,4,7 days. There were no serious adverse events observed in any patient and the engineered antibody cleared rapidly from blood within 12 hours. There was consistently high uptake seen by PET imaging into tumour with, importantly, no antibody uptake in normal tissues, including liver and kidney. High tumor uptake was seen in metastases in both liver and lymph nodes, as soon as 1-2 days post injection. There was No immunogenicity seen against PEG-AVP0458. Conclusions: PEG-AVP0458 is safe, and demonstrates excellent, rapid targeting of tumor in man, with no specific normal organ uptake, and very high tumor: blood ratios. This data demonstrates the feasibility of using PEG-diabodies for imaging and for delivery of radioisotopes (RIT) or cytotoxic drug payloads (ADC) in cancer patients.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 6
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.
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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method