Using 18F-FSPG PET and ctDNA to guide Y90 treatment for hepatocellular carcinoma

Phase 1, Single-site, Single-arm, Clinical Imaging, and Blood-based Biomarker Trial Utilizing 18F-FSPG PET to Guide Therapy in Hepatocellular Carcinoma

This will test whether a special PET scan (18F-FSPG) plus blood ctDNA can predict and detect response to Y90 radioembolization in people with hepatocellular carcinoma.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: M.D. Anderson Cancer Center (Academic / other)
• Drugs / interventions: Radiation
• Locations: 1 site (Houston, Texas)
• Trial ID: NCT07116486 on ClinicalTrials.gov

What this trial studies

This single-center Phase 1 interventional study at MD Anderson uses the radiotracer 18F-FSPG PET and serial circulating tumor DNA (ctDNA) measurements before and after Y90 radioembolization. Participants receive a pre-treatment 18F-FSPG PET scan and blood draws, then undergo standard-of-care Y90 treatment with follow-up imaging and blood tests at 3, 6, 9, and 12 months. The study will compare changes in 18F-FSPG uptake and ctDNA levels to conventional imaging outcomes, evaluate visualization of residual disease, and perform voxel-wise analyses of tracer accumulation. Response will be evaluated using mRECIST and LI-RADS criteria to explore whether PET and ctDNA provide earlier or complementary indicators of treatment effect.

Who should consider this trial

Good fit: Adults with hepatocellular carcinoma who meet LI-RADS 4–5 or have pathologic or angiographic confirmation and who are candidates for Y90 radioembolization monotherapy are the intended participants.

Not a fit: Patients who are not candidates for Y90 radioembolization, who have contraindications to PET/radiopharmaceuticals, or who cannot travel to the treating center are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, these imaging and blood markers could help doctors predict who will respond to Y90 and detect residual disease earlier so treatment can be adjusted sooner.

How similar studies have performed: ctDNA assays and novel PET tracers have shown promise separately in cancer, but combining 18F-FSPG PET with ctDNA to guide Y90 in HCC is largely novel and not yet well established.

Eligibility criteria

Inclusion Criteria:

1. Diagnosis of HCC with one or more of the following:

   1. Liver mass with non-rim arterial phase hyperenhancement (APHE) and one of the following:

      1. 10-19 mm with ≥ 2 additional major features according to LI-RADS criteria ("washout", enhancing "capsule", and/or threshold growth),
      2. 10-19 mm with "washout" and visibility at antecedent ultrasound (US) but with no "capsule" or threshold growth,
      3. 10-19 mm with ≥50% size increase in ≤6 months but with no "washout" or "capsule" or
      4. ≥20 mm with ≥1 additional major feature according to LI-RADS criteria ("washout", enhancing "capsule", or threshold growth).
   2. Lesions that meet LI-RADS 4 criteria or
   3. Lesions that meet LI-RADS 5 criteria or
   4. Suggestive imaging findings plus Alpha Fetoprotein (AFP) \> 200 mg/dL or
   5. Tumor confirmed by arteriography or
   6. Pathologic confirmation of tumor and
2. Patients with HCC must be a candidate for Y90 radioembolization monotherapy. and
3. Each patient must have completed conventional imaging and staging and CT before initiation of the investigational PET studies.
4. Age ≥18 years. Because no dosing or adverse event data are currently available on the use of 18F-FSPG in patients \<18 years of age, children are excluded from this study.
5. The effects of 18F-FSPG on the developing human fetus are unknown. For this reason women and men of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. (Refer to Pregnancy Assessment Policy MD Anderson Institutional Policy # CLN1114). This includes all female patients, between the onset of menses (as early as 8 years of age) and 55 years unless the patient presents with an applicable exclusionary factor which may be one of the following:

   * Postmenopausal (no menses in greater than or equal to 12 consecutive months).
   * History of hysterectomy or bilateral salpingo-oophorectomy.
   * Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy).
   * History of bilateral tubal ligation or another surgical sterilization procedure.

     * Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
     * Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of 18F-FSPG administration.
6. Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

1. Patients under the age of 18 will be excluded from the this study.
2. Patients who have HCC but are not candidates for Y90 radioembolization monotherapy.
3. Pregnant and breastfeeding patients. Pregnant women are excluded from this study because 18F-FSPG as a radiotracer has a potential teratogenic or abortifacient effect. Because there is an unknown but potential risk for adverse events in nursing infants secondary to administration of the tracer 18F-FSPG to the mother, breastfeeding should be discontinued.
4. Patients with poorly controlled diabetes mellitus (fasting blood glucose level \> 200 mg/dL).
5. Patients with psychiatric illness/social situations that would limit compliance with study requirements.
6. Patients who have not recovered from AEs or had allergic reactions to similar compounds should be excluded.

Where this trial is running

Houston, Texas

• The University of Texas M. D. Anderson Cancer Center — Houston, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Simone Krebs, MD — M.D. Anderson Cancer Center
• Study coordinator: Simone Krebs, MD

Conditions Hepatocellular Carcinoma