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)

Studien-Informationen Einschlusskriterien Studien-Rationale Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT04536454

Studienbeginn:
April 2021

Letztes Update:
11.05.2021

Wirkstoff:
[18F]FPyGal

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
University Hospital Tuebingen

Collaborator:
-

Studienleiter

Lars Zender, MD
Study Director
University Hospital of Tübingen

Kontakt

Christian la Fougere, MD
Kontakt:
Phone: +49-7071 29-0
E-Mail: christian.lafougere@med.uni-tuebingen.de» Kontaktdaten anzeigen

Ulrich M Lauer, MD
Kontakt:
Phone: +49-7071 29-0
E-Mail: ulrich.lauer@med.uni-tuebingen.de» Kontaktdaten anzeigen

Studienlocations
(1 von 1)

University Hospital of Tübingen
72076 Tübingen
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Christian la Fougere, MD
Phone: +49 7071 29-86553
E-Mail: christian.lafougere@med.uni-tuebingen

Lars Zender, MD
Phone: +49 7071 29-83675
E-Mail: lars.zender@med.uni-tuebingen.de» Ansprechpartner anzeigen

Studien-Informationen

Detailed Description:

The so-called tumor senescence is described as a resistance mechanism, which can be the basis

for the non-response to most common chemotherapies. It is believed that the identification of

so-called senescent tumors could improve treatment strategies for solid tumors and, in

particular, avoid inefficient treatment of patients with highly toxic drugs.

The aim of this study is to investigate the safety, radiation exposure (dosimetry) and

diagnostic accuracy of the novel diagnostic substance [18F]FPyGal if it is used before tumor

imaging imaging (here: positron emission tomography combined with magnetic resonance imaging

(PET / MRT) or in combination with computed tomography (PET / CT)).

Diagnostic substances used in imaging such as [18F]FPyGal are known as radiotracers, since

their distribution in the tumor tissue can provide information about the special tumor

biological processes taking place there.

In the context of this study, it is of particular interest to find out whether it is possible

to use the novel radiotracer [18F]FPyGal to detect areas after standard tumor therapy that

contain particularly resistant (therapy-resistant) tumor cells. This resistance phenomenon in

tumor tissues, which may be visualized with the radiotracer [18F]FPyGal, is called tumor

senescence.

The latest research results show that senescent tumor cells can not only evade different

forms of chemotherapy or radiation therapy. Senescent tumor cells can also cause the cancer

to come back later. That is why current therapeutic research is concentrating on developing

new approaches to combat such senescent tumor cells. For this it is relevant to be able to

first diagnose senescent tumor cells as well as possible using imaging.

Ein-/Ausschlusskriterien

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

Studien-Rationale

Primary outcome:

1. Incidence and severity of adverse events (AEs) (Time Frame - 7 days):
Incidence and severity of adverse events (AEs) (CTCAE V5.0) over 7 days Grade 1: no interruption; Grade 2: interrupt until Grade 0/1; Grade 3 and >3: interruption of study

Secondary outcome:

1. Number of patients exhibiting positive signals for senescent tumor cells in PET-imaging and/or tumor histopathology (Time Frame - through study completion, an average of 6 month):
Positive [18F]FPyGal-PET-imaging of patient's tumor will be correlated with histopathology using senescence specific biomarkers against SABG (senescence-associated ß-galactosidase), p16, p21, and p53

Geprüfte Regime

[18F]FPyGal (non-invasive imaging of tumor senescence):
Radiotracer for PET-imaging

Quelle: ClinicalTrials.gov

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