Description:
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).
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).
Recruiting
Early Phase 1
| Drug | Synonyms | Arms |
|---|---|---|
| [68Ga]Ga DOTA-5G and [177Lu]Lu DOTA-ABM-5G. | [68Ga]Ga DOTA-5G, [177Lu]Lu DOTA-ABM-5G, [68Ga]Ga DOTA-5G and [177Lu]Lu DOTA-ABM-5G theranostic pair | Recommended Phase 2 dose [177Lu]Lu DOTA-ABM-5G therapy study |
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.
| Name | Type | Description | Interventions |
|---|---|---|---|
| [177Lu]Lu DOTA-ABM-5G dose escalation therapy study | Experimental | Patients will be undergo [68Ga]Ga DOTA-5G PET/CT scans to confirm eligibility for the [177Lu]Lu DOTA-ABM-5G therapy. Patients with sufficient lesion uptake of [68Ga]Ga DOTA-5G PET/CT will be offered therapy. Escalating doses of 25-200 mCi of [177Lu]Lu DOTA-ABM-5G will be administered in a traditional 3+3 dose escalation design. After escalation, 10 additional patients will be enrolled into a dose expansion cohort. |
|
| Recommended Phase 2 dose [177Lu]Lu DOTA-ABM-5G therapy study | Experimental | Patients will be undergo [68Ga]Ga DOTA-5G PET/CT scans to confirm eligibility for the [177Lu]Lu DOTA-ABM-5G therapy.10 patients will be enrolled in the dose expansion cohort and recieve the highest dose achieved in the [177Lu]Lu DOTA-ABM-5G dose escalation therapy study |
|
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 Exclusion Criteria:
1. Participant on any chemical anticoagulant including antiplatelet agents
(excluding ASA)
2. Participants with Class 3 or 4 NYHA Congestive Heart Failure
3. Clinically significant bleeding within two weeks prior to trial entry (e.g.
gastrointestinal bleeding, intracranial bleeding)
4. Pregnant or lactating women
5. Major surgery, defined as any surgical procedure that involves general anesthesia
and a significant incision (i.e. larger than what is required for placement of a
central venous access, percutaneous feeding tube, or biopsy) within 28 days prior
to study day 1 or anticipated surgery within the subsequent 6 weeks
6. Has an additional active malignancy requiring therapy within the past 2 years
7. Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic
therapy
8. Psychiatric illness/social situations that would interfere with compliance with
study requirements
9. Previous radiation therapy for the treatment of advanced or metastatic disease
10. Cannot undergo PET/CT scanning because of weight limits (350 lbs)
11. INR>1.2; PTT>5 seconds above UNL
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| Measure: | [68Ga]Ga DOTA-5G PET/CT imaging |
| Time Frame: | 2 hours from time of injection |
| Safety Issue: | |
| Description: | Assessment of [68Ga]Ga DOTA-5G PET/CT imaging to detect lesions in patients with locally advanced or metastatic pancreatic cancer |
| Measure: | Assessment of organ dosimetry of [177Lu]Lu DOTA-ABM-5G |
| Time Frame: | 7-14 days from time of injection |
| Safety Issue: | |
| Description: | Assessment of organ dosimetry of [177Lu]Lu DOTA-ABM-5G using SPECT/CT imaging at various timepoints |
| Phase: | Early Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | University of California, Davis |
March 24, 2021