Clinical trial NCT06894745: PET [89Zr]DFO-starPEG in Solid Tumors
Official title: Positron Emission Tomography (PET) Imaging of the Enhanced Permeability and Retention (EPR) Effect With [89Zr]DFO-starPEG in Patients With Solid Tumors
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Solid Tumor
Solid Carcinoma
Soft Tissue Lesion
Keywords: Dosimetry
Imaging
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: ProLynx LLC
name: National Cancer Institute (NCI)
First posted: 2025-03-25
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: This is a first-in-human, pilot study of the novel PET-imaging radiotracer \[89Zr\]DFO-starPEG. The study is designed to obtain preliminary data to support future development of this agent as an imaging surrogate to visualize enhanced permeability and retention (EPR)-mediated tracer uptake before administration of EPR-based nanomedicines.

Detailed description: PRIMARY OBJECTIVES:

I. To descriptively report patterns of \[89Zr\]DFO-starPEG uptake on whole-body PET (Cohorts A \& B).

II. To determine the radiation dosimetry following \[89Zr\]DFO-starPEG administration (Cohort A).

SECONDARY OBJECTIVES:

I. To determine the safety of \[89Zr\]DFO-starPEG (Cohorts A \& B).

EXPLORATORY OBJECTIVES:

I. To study the pharmacokinetics of \[89Zr\]DFO-starPEG and estimate its half-life (Cohort A).

OUTLINE:

Participants will be assigned to one of 2 cohorts:

* COHORT A: Participants will receive multiple scans over time
* COHORT B: Participants will receive a scan at a single time point

Participants will be followed for adverse events for approximately 1 week after radiotracer administration until the Day 5-9 visit.

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.

Primary outcomes:
measure: Median Maximum Standardized Uptake Value (SUVmax) by cohort
timeFrame: Up to 9 days
measure: Tumor-to-background signal ratio (muscle)
timeFrame: Up to 9 days
measure: Tumor-to-background signal ratio (blood)
timeFrame: Up to 9 days
measure: Mean absorbed dose of PET [89Zr]DFO-starPEG (Cohort A)
timeFrame: Up to 9 days
Secondary outcomes:
measure: Proportion of participants with treatment-emergent adverse events
timeFrame: Up to 9 days
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
Study officials:
affiliation: University of California, San Francisco
name: Robert Flavell, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: