Clinical trial NCT04665947: First-in-human Study of the Theranostic Pair [68Ga]Ga DOTA-5G and [177Lu]Lu DOTA-ABM-5G in Pancreatic Cancer
Official title: First-in-human Study of the Theranostic Pair [68Ga]Ga DOTA-5G and [177Lu]Lu DOTA-ABM-5G in Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Metastatic Pancreatic Cancer
Locally Advanced Pancreatic Adenocarcinoma
Keywords: integrin
metastatic pancreatic cancer
PET
theranostic
Lead sponsor: University of California, Davis
Sponsor class: OTHER
First posted: 2020-12-14
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: This is a first-in-human 3 + 3 study design to identify dose limiting toxicity and recommended phase 2 dose
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: [68Ga]Ga DOTA-5G PET/CT imaging
timeFrame: 2 hours from time of injection
measure: [177Lu]Lu DOTA-ABM-5G dose escalation therapy
timeFrame: 30 days from time of injection
Secondary outcomes:
measure: Assessment of organ dosimetry of [177Lu]Lu DOTA-ABM-5G
timeFrame: 7-14 days from time of injection
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: University of California Davis
state: California
Study officials:
affiliation: University of California, Davis
name: Julie L Sutcliffe
role: PRINCIPAL_INVESTIGATOR
References: