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

Overview

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.

Interventions

• Drug [68Ga]Ga DOTA-5G and [177Lu]Lu DOTA-ABM-5G.
  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. Patients will undergo a follow up \[68Ga\]Ga DOTA-5G PET/CT scans to assess tretament efficacy.

Primary outcome measures

• [68Ga]Ga DOTA-5G PET/CT imaging [Time frame: 2 hours from time of injection]

Secondary outcome measures (2)

• [177Lu]Lu DOTA-ABM-5G treatment [Time frame: 30 days from time of treatment]
• [177Lu]Lu DOTA-ABM-5G treatment efficacy [Time frame: 60 days from time of treatment]

Eligibility criteria

Inclusion criteria

\[68Ga\]Ga DOTA-5G PET/CT Inclusion Criteria:

• Ability to understand and willingness to sign a written informed consent document.
• Age 18 or more years
• Pathologically confirmed GU, GI, GYN 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)
• 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.
• Available archival tumor tissue (excisional, core, or FNA is acceptable). Tissue from a metastatic site is preferred when available.
• Eastern Cooperative Oncology Group Performance Status ≤ 2
• 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.
• 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:

• Completion of entry into \[68Ga\]Ga DOTA-5G PET study and completion of scan
• 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:

• Participants with Class 3 or 4 NYHA Congestive Heart Failure
• Clinically significant bleeding within two weeks prior to trial. entry (e.g. gastrointestinal bleeding, intracranial bleeding)
• Pregnant or lactating women
• 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
• 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)
• Active, uncontrolled bacterial, viral, or fungal infection(s) despite systemic therapy
• Psychiatric illness/social situations that would interfere with compliance with study requirements
• Cannot undergo PET/CT or SPECT/CT scanning because of weight limits (350 lbs.)
• Pathologically confirmed NSCLC with metastatic disease
• INR >2.0: PTT>15 seconds above ULN
• Participant on therapeutic warfarin anticoagulation
• External beam radiation therapy (EBRT) or radiopharmaceutical treatment within 21 days prior to study day 1

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• The University of California Davis Comprehensive Cancer Center — Sacramento

Identifiers

NCT: NCT06389123 · 1788760

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗