Clinical trial NCT06389123: Molecularly Targeted Theranostic Approach for the Detection and Treatment of Metastatic Carcinomas
Official title: A Novel Molecularly Targeted Theranostic Approach Via the αvβ6 Integrin for the Detection and Treatment of Metastatic Carcinomas
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Metastatic Cancer
Keywords: integrin
PET
Theranostics
metastatic cancer
Lead sponsor: University of California, Davis
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
First posted: 2024-04-29
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single treatment
Primary purpose: TREATMENT

Brief summary: This is a Phase I study to evaluate the safety and efficacy of the \[68Ga\]Ga DOTA-5G and \[177Lu\]Lu DOTA-ABM-5G theranostics pair in patients with metastatic cancer.

Detailed description: This is a Phase I study to evaluate the safety and efficacy of the \[68Ga\]Ga DOTA-5G and \[177Lu\]Lu DOTA-ABM-5G theranostics pair in patients with metastatic cancer. \[68Ga\]Ga DOTA-5G PET/CT will be used to identify and stratify patients eligible for (and most likely to respond to) the \[177Lu\]Lu DOTA-ABM-5G therapy. Up to 40 patients will be enrolled over a 36-month period with metastatic cancer with a life expectancy of at least 3 months, who demonstrate disease progression after at least 1 prior treatment for metastatic disease and have available archival tissue.

The hypothesis are that a) \[68Ga\]Ga DOTA-5G will detect lesions in patients with metastatic cancer, b) the theranostic pair \[68Ga\]Ga DOTA-5G/ \[177Lu\]Lu DOTA-ABM-5G will be safe and well tolerated, and c) a therapeutic response will be achieved with a single dose of \[177Lu\]Lu DOTA-ABM-5G.

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. Pathologically confirmed GU, GI, breast, cervical, uterine, or head and neck cancers with metastatic disease and 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 for metastatic disease during or following at least one prior FDA approved systemic regimen (Androgen Deprivation allowed) as established by diagnostic imaging.
5. Available archival tumor tissue (excisional, core, or FNA is acceptable). Tissue from a metastatic site is preferred when available.
6. Eastern Cooperative Oncology Group Performance Status ≤ 2
7. Participant must have completed prior systemic therapy 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.
8. Hematologic parameters defined as:

Absolute neutrophil count (ANC) ≥ 1000 cells/mm3 Platelet count ≥ 100,000/mm3 Hemoglobin ≥ 8 g/dL

Blood chemistry levels defined as:

AST, ALT, alkaline phosphatase ≤ 5 times upper limit of normal (ULN) Total bilirubin ≤ 2 times ULN Creatinine ≤ 2 times ULN 10. Anticipated life expectancy ≥ 3 months 11. 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 bone, brain, lung or liver and identified on standard of care diagnostic imaging)

Exclusion Criteria:

\[68Ga\]Ga DOTA-5G and \[177Lu\]Lu DOTA-ABM-5G therapy Exclusion Criteria:

1. Participants with Class 3 or 4 NYHA Congestive Heart Failure
2. Clinically significant bleeding within two weeks prior to trial. entry (e.g. gastrointestinal bleeding, intracranial bleeding)
3. Pregnant or lactating women
4. 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
5. Has an additional active malignancy requiring therapy within the past 2 years (other than early stage, surgically managed basal and squamous skin cancer and in situ malignancies of the breast and cervix)
6. Active, uncontrolled bacterial, viral, or fungal infection(s) despite systemic therapy
7. Psychiatric illness/social situations that would interfere with compliance with study requirements
8. Cannot undergo PET/CT or SPECT/CT scanning because of weight limits (350 lbs.)
9. Pathologically confirmed NSCLC with metastatic disease
10. INR \>2.0: PTT\>15 seconds above ULN
11. Participant on therapeutic warfarin anticoagulation
12. External beam radiation therapy (EBRT) or radiopharmaceutical treatment within 21 days prior to study day 1

Primary outcomes:
measure: [68Ga]Ga DOTA-5G PET/CT imaging
timeFrame: 2 hours from time of injection
Secondary outcomes:
measure: [177Lu]Lu DOTA-ABM-5G treatment
timeFrame: 30 days from time of treatment
measure: [177Lu]Lu DOTA-ABM-5G treatment efficacy
timeFrame: 60 days from time of treatment
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: The University of California Davis Comprehensive Cancer Center
state: California
Study officials:
affiliation: University of California, Davis
name: Julie L Sutcliffe
role: PRINCIPAL_INVESTIGATOR
References: