Study to Assess Safety and PET Imaging Characteristics of a Novel Senescence-specific Radiotracer [18F]FPyGal (2-[Fluorine-18]Fluoro-3-pyridinyl-β-D-galactopyranoside)

• Status: Recruiting
• Trial end date: 2024-06-01
• Target enrollment: 0
• Participant gender: All

Summary

It is of particular interest to find out whether it is possible to use the novel radiotracer [18F]FPyGal to be tested to detect areas after standard tumor therapy that contain resistant (therapy-resistant) tumor cells. This resistance phenomenon in tumor tissues, which may be visualized with the radiotracer [18F]FPyGal, is called tumor senescence.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospital Tuebingen

Criteria

Inclusion Criteria:

• Male or female patients ≥ 18 years of age at the time of signing the informed consent

• Patients with locally advanced primary non-operable solid tumors (AEGs, rectum cancers, NSCLCs, NUT midline carcinomas (NMC))

• Eastern Cooperative Oncology Group Performance (ECOG) Status ≤ 2

• Adequate bone marrow, renal, and hepatic function defined by laboratory tests within 14 days prior to study treatment:

• Neutrophil count ≥ 1,500/mm3

• Platelet count ≥ 100,000/µl

• Bilirubin ≤ 1.5 x upper limit of normal (ULN)

• ALT (alanine transaminase) and AST (aspartate transaminase) ≤ 2.5 x ULN

• PT-INR (prothrombin time and international normalized ratio) /PTT (partial thromboplastin time)= ≤ 1.5 x ULN

• Creatine kinase ≤ 2.5 x ULN

• Serum creatinine ≤ 1.5 mg/dl or creatinine clearance ≥ 60 ml/min

• Patients scheduled for neo-adjuvant (radio-) chemotherapy and subsequent tumor surgery (Groups a-c) or tumor biopsy (Group d)

• Understand and voluntarily sign an informed consent document prior to any study related assessments/ procedures.

• Able to adhere to the study visit schedule and other protocol requirements

• Consent to practice double-barrier contraception until end of the study (28 days after last [18F]FPyGal injection)

• Females of childbearing potential (FCBP) must agree

• to use two reliable forms of contraception simultaneously or practice complete abstinence from heterosexual contact for at least 28 days before starting study drug, while participating in the study (including dose interruptions), and for at least 28 days after end of study treatment and must agree to pregnancy testing during this timeframe

• to abstain from breastfeeding during study participation and 7 days after end of study drug administration.

• Males must agree

• to use a latex condom during any sexual contact with FCBP while participating in the study and for at least 28 days after end of study treatment, even if he has undergone a successful vasectomy

• to refrain from donating semen or sperm while participating in the study and for at least 28 days after end of study treatment.

Exclusion Criteria:

• Any contraindication for MRI (impaired renal function and / or known hypersensitivity to gadolinium-containing contrast agent are not considered as contraindication, since then imaging will be performed without gadolinium contrast agent).

• Known hypersensitivity to [18F]FPyGal or its components or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product

• Administration of any kind of PET tracer within a period corresponding to 8 half-lives of the representative radionuclide (e.g. for fluorine-18: 109.77 min, 8x109.77 min =14.7 h)

• Persistent toxicity (>Grade 2) according to Common Terminology Criteria for Adverse Events [CTCAE] version 5.0, caused by previous cancer therapy, excluding alopecia

• Clinical signs of active infection (> Grade 2 according to CTCAE version 5.0)

• History of HIV infection

• Immunocompromised patients

• Active or chronic viral hepatitis (HBV or HCV)

• History of autoimmune disease

• History of relevant CNS pathology or current relevant CNS (central nervous system) pathology (e.g. seizure, paresis, aphasia, cerebrovascular ischemia/hemorrhage, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis, coordination or movement disorder) Epilepsy requiring pharmacologic treatment

• Therapeutic anticoagulation therapy

• Major surgery within 4 weeks of starting study treatment. Patients must have recovered from any effects of major surgery.

• Patients receiving any systemic chemotherapy or radio-therapy within 2 weeks prior to study treatment or a longer period depending on the defined characteristics of the agents used

• Heart failure NYHA (New York Heart Association) III/IV

• Severe obstructive or restrictive ventilation disorder

• Known history of GI-perforation

• Patients not able to declare meaningful informed consent on their own

• Women during pregnancy and lactation; female patients of childbearing potential or male patients with female partners of childbearing potential not willing to practice effective contraception by using a double-barrier method from Day 0 until 28 days post-dose.

• Male patients planning to donate sperm while participating in the study and for at least 28 days after end of study treatment.

• Participation in other clinical trials or observation period of competing trials