PET imaging with [89Zr]DFO-starPEG for solid tumors

Positron Emission Tomography (PET) Imaging of the Enhanced Permeability and Retention (EPR) Effect With [89Zr]DFO-starPEG in Patients With Solid Tumors

We will test a new PET imaging tracer called [89Zr]DFO-starPEG in adults with measurable solid tumors to see if it highlights tumor uptake and is safe.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 13 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of California, San Francisco (Academic / other)
• Drugs / interventions: radiation
• Locations: 1 site (San Francisco, California)
• Trial ID: NCT06894745 on ClinicalTrials.gov

What this trial studies

This is a first-in-human, pilot, phase 1 protocol administering the novel radiotracer [89Zr]DFO-starPEG to adults with histologically confirmed solid tumors. Participants are assigned to one of two cohorts: Cohort A undergoes multiple whole-body PET scans over time to define uptake patterns and radiation dosimetry and to characterize pharmacokinetics, while Cohort B has a single-time-point PET scan. Safety and adverse events are monitored for about one week after tracer administration, with specimen collection for pharmacokinetic analysis. The imaging is intended to identify enhanced permeability and retention (EPR)-mediated tracer uptake as a potential surrogate for EPR-based nanomedicine delivery.

Who should consider this trial

Good fit: Adults (≥18 years) with histologically or cytologically confirmed solid tumor malignancy and at least one soft tissue lesion ≥1 cm on imaging, who are able to undergo PET/CT, have ECOG ≤2 (or Karnofsky ≥50%), and meet specified organ function criteria.

Not a fit: Patients without a measurable soft tissue lesion ≥1 cm, those with inadequate organ function, or those unable to undergo PET/CT (including pregnancy) are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, the tracer could help identify which patients' tumors concentrate EPR-targeted nanomedicines, potentially guiding therapy selection.

How similar studies have performed: This specific [89Zr]DFO-starPEG tracer is being tested in humans for the first time, though other 89Zr-labeled agents and EPR-directed imaging approaches have been explored preclinically and in limited clinical contexts.

Eligibility criteria

Inclusion Criteria:

1. Histological or cytological confirmation of solid tumor malignancy.
2. Any solid tumor malignancy, with at least one soft tissue lesion measurable at 1 centimeter (cm) or greater in short axis measurement on cross sectional imaging such as Computerized tomography (CT), Magnetic resonance imaging (MRI), or Positron Emission Tomography (PET)/CT.
3. Clinically able to undergo PET/CT imaging.
4. Age \>= 18 years.
5. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 or Karnofsky ≥ 50%.
6. Adequate organ function as defined below within 0-28 days before \[89Zr\]DFO-starPEG administration:

   * Total bilirubin: ≤ 1.5 x institutional upper limit of normal (ULN) (unless elevated due to Gilbert's syndrome and direct bilirubin is within normal limits) .
   * Aspartate aminotransferase (AST)/ serum glutamic-oxaloacetic transaminase (SGOT) ≤ 3 x ULN.
   * Alanine aminotransferase (ALT)/ serum glutamic-pyruvic transaminase (SGPT) ≤ 3 x ULN.
   * Estimated creatinine clearance: ≥ 60 mL/min, calculated using the Cockcroft-Gault equation or 24 hour urine collection.
7. Females of reproductive potential (defined below) must be willing to undergo a urine or serum pregnancy test (i.e., human chorionic gonadotropin test) within 72 hours before administration of \[89Zr\]DFO-starPEG. A female is considered to NOT be of reproductive potential (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice), if they meet either of the following two criteria: (1) has reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause); or (2) has undergone surgical sterilization (i.e., hysterectomy and/or bilateral oophorectomy for removal of uterus and/or ovaries). The result of the urine or serum pregnancy test must be negative in order to initiate the \[89Zr\]DFO-starPEG administration. If a urine pregnancy test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the individual must be excluded from participation if the serum pregnancy result is positive. Pregnant individuals are excluded from this study because there is an unknown but potential risk for adverse effects in the unborn child secondary to treatment of the study participant with \[89Zr\]DFO-starPEG.
8. Individuals with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or endpoints of this study are eligible.
9. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

1. Individuals with a contraindication to PET-CT imaging (e.g., severe claustrophobia).
2. Individuals who are pregnant or breastfeeding/chestfeeding. Pregnant and breastfeeding/chestfeeding individuals are excluded because there is an unknown but potential risk for adverse effects in the unborn/nursing child secondary to treatment of the study participant with \[89Zr\]DFO-starPEG. Females of childbearing potential must have a negative pregnancy test before administration of \[89Zr\]DFO-starPEG, as outlined in inclusion criterion #7. Breastfeeding/chestfeeding should be discontinued before administration of \[89Zr\]DFO-starPEG.
3. Individuals who do not agree to follow the below contraception requirements:

   * Females of reproductive potential (defined below) must agree to use two forms of contraception, consisting of a barrier method (such as condoms) in combination with a secondary complementary method (such as hormonal, intrauterine device (IUD), etc.), or strict abstinence, for the duration of study participation and for 1 month after administration of \[89Zr\]DFO-starPEG.
   * A female is considered to NOT be of reproductive potential (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice), if they meet either of the following two criteria: (1) has reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause); or (2) has undergone surgical sterilization (i.e., hysterectomy and/or bilateral oophorectomy for removal of uterus and/or ovaries).
4. Hypersensitivity to \[89Zr\]DFO-starPEG or any of its excipients.
5. Individuals with any condition or social circumstance that, in the opinion of the investigator, would impair the participant's ability to comply with study procedures.

Where this trial is running

San Francisco, California

• University of California, San Francisco — San Francisco, California, United States (Recruiting)

Study contacts

• Principal investigator: Robert Flavell, MD, PhD — University of California, San Francisco
• Study coordinator: Maya Aslam

Conditions Solid Tumor; Solid Carcinoma; Soft Tissue Lesion; Dosimetry; Imaging