Locally Advanced Pancreatic Adenocarcinoma, Metastatic Pancreatic Cancer
Conditions
Keywords
integrin, metastatic pancreatic cancer, PET, theranostic
Brief summary
This is a Phase I, first-in-human study to evaluate the safety and efficacy of the \[68Ga\]Ga DOTA-5G and \[177Lu\]Lu DOTA-ABM-5G theranostic pair in patients with locally advanced or metastatic pancreatic adenocarcinoma (PDAC).
Detailed description
This is a Phase I, first-in-human study to evaluate the safety and efficacy of the \[68Ga\]Ga DOTA-5G /\[177Lu\]Lu DOTA-ABM-5G theranostic pair in patients with locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC). PET imaging using \[68Ga\]Ga DOTA-5G will be used to diagnose patients who are eligible for the \[177Lu\]Lu DOTA-ABM-5G. The overall purpose of this study is to identify the dose limiting toxicity (DLT) and recommended phase 2 dose (RP2D) of \[177Lu\]Lu DOTA-ABM-5G. A 3+3 study design in is proposed to identify the RP2D of \[177Lu\]Lu DOTA-ABM-5G. An expansion group will receive the RP2D in order to obtain initial estimates of response and additional information on safety of \[177Lu\]Lu DOTA-ABM-5G. The hypotheses of this phase I study are that a) \[68Ga\]Ga DOTA-5G will detect lesions in patients with locally advanced or metastatic pancreas cancer b) the theranostic pair \[68Ga\]Ga DOTA-5G/ \[177Lu\]Lu DOTA-ABM-5G will be safe and well tolerated c) we will be able to identify a Recommended Phase 2 Dose (RP2D) for \[177Lu\]Lu DOTA-ABM-5G therapy to be used in subsequent Phase II trials.
Interventions
PET imaging using \[68Ga\]Ga DOTA-5G will be used to diagnose patients who are eligible for treatment with the \[177Lu\]Lu DOTA-ABM-5G.
Sponsors
University of California, Davis
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a first-in-human 3 + 3 study design to identify dose limiting toxicity and recommended phase 2 dose
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
\[68Ga\]Ga DOTA-5G PET/CT Inclusion Criteria: 1. Ability to understand and willingness to sign a written informed consent document. 2. Age 18 or more years 3. Confirmed presence of locally advanced, unresectable or metastatic pancreatic adenocarcinoma (other pancreatic malignant histologies are excluded) with measurable disease per RECIST (version 1.1) (i.e. at least 1 lesion \> 1 cm or lymph node \> 1.5 cm in short axis) 4. Participant must have documented tumor progression during or following at least one prior systemic regimen as established by CT or MRI scan within 28 days of enrollment 5. Eastern Cooperative Oncology Group Performance Status ≤ 2 6. Participant must have completed prior chemotherapy at least 2 weeks (washout period) prior to \[68Ga\]Ga DOTA-5G PET scan. Any clinically significant toxicity (with the exceptions of hair loss and sensory neuropathy) related to prior therapy resolved to Grade 1 or baseline. 7. Hematologic parameters defined as: 1. Absolute neutrophil count (ANC) ≥ 1000 cells/mm3 2. Platelet count ≥ 100,000/mm3 3. Hemoglobin ≥ 8 g/dL 8. Blood chemistry levels defined as: 1. AST, ALT, alkaline phosphatase ≤ 5 times upper limit of normal (ULN) 2. Total bilirubin ≤ 2 times ULN 3. Creatinine ≤ 2 times ULN 9. Anticipated life expectancy ≥ 3 months 10. Able to remain motionless for up to 30-60 minutes per scan \[177Lu\]Lu DOTA-ABM-5G therapy Inclusion Criteria: 1. Completion of entry into \[68Ga\]Ga DOTA-5G PET study and completion of scan 2. The presence of at least one measurable disease by \[68Ga\]Ga DOTA-5G PET/CT (SUVmax\>2-fold above normal lung or liver)
Exclusion criteria
* \[68Ga\]Ga DOTA-5G and \[177Lu\]Lu DOTA-ABM-5G therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| [68Ga]Ga DOTA-5G PET/CT imaging | 2 hours from time of injection | Assessment of \[68Ga\]Ga DOTA-5G PET/CT imaging to detect lesions in patients with locally advanced or metastatic pancreatic cancer |
| [177Lu]Lu DOTA-ABM-5G dose escalation therapy | 30 days from time of injection | Frequency of dose-limiting toxicities (DLT) of \[177Lu\]Lu DOTA-ABM-5G at escalating dose levels of \[177Lu\]Lu DOTA-ABM-5G |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of organ dosimetry of [177Lu]Lu DOTA-ABM-5G | 7-14 days from time of injection | Assessment of organ dosimetry of \[177Lu\]Lu DOTA-ABM-5G using SPECT/CT imaging at various timepoints |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJulie L Sutcliffe
University of California, Davis
Outcome results
None listed