A study to assess the safety and efficacy of L19TNF plus standard radiotherapy and temozolomide in patients with newly diagnosed glioblastoma.
Résumé de l'étude
We want to investigate what the optimal dose of L19TNF in combination with standard radiotherapy and temozolomide is, how well the drug is tolerated in glioblastoma, and whether the combination therapy improves survival rates. L19TNF is a new investigational substance with potential anticancer activity. This drug is comparable to the cancer drug TNF (BeromunTM). Unfortunately, the systemic application of TNF is associated with numerous side effects, including a (severe) dose-dependent hypotensive effect, which can sometimes lead to dysfunctions of the heart and lungs. In this study, however, TNF is linked to the substance L19, which directs TNF directly to the tumor. In this way, a higher concentration of TNF in the tumor is to be achieved, thus reducing side effects while maintaining the same efficacy. L19TNF is an unapproved drug.
(BASEC)
Intervention étudiée
First, the doctor will carefully examine and interview potential candidates to determine if they are eligible to participate in the study (screening). Each patient will receive the recognized standard therapy for newly diagnosed glioblastoma. This consists of a 6-week chemoradiotherapy, where treatment is given with radiotherapy and temozolomide. This is followed by a 4-week treatment break and a maintenance therapy, where only temozolomide is administered. In the first part of the study (Phase I), 5 patient groups (of 3-6 patients each) will be treated with an increasing dose of L19TNF, in the form of an intravenous infusion over two hours, in addition to the standard therapy. The first two groups will receive L19TNF on days 1, 3, and 5 of each 28-day treatment cycle of the maintenance therapy. The subsequent 3 groups will also receive L19TNF during chemoradiotherapy, on days 1, 3, 5, 22, 24, and 26 of treatment. In the second part of the study (Phase II), all patients will be treated with L19TNF, temozolomide, and standard radiotherapy. The dose and frequency of L19TNF administration will be based on the treatment regimen that was best tolerated in Phase I. In the third part of the study (Phase IIb), half of the patients will be treated with the recognized standard therapy (radiotherapy + temozolomide), while the other half will additionally receive L19TNF according to the same scheme as in Phase II. For all study participants, the response of their cancer to treatment will be checked every three treatment cycles. When they come to the clinic for study treatments during these cycles, further examinations will be conducted to check whether the tumor responds to treatment and whether any symptoms or side effects occur. For this purpose, imaging using magnetic resonance imaging (MRI) will be performed, and blood and urine will be taken from study participants at regular intervals for laboratory tests. Each study participant can receive a maximum of 6 treatment cycles of maintenance therapy. The duration of a patient's participation in the study depends on how well the tumor responds to treatment and how well the treatment is tolerated.
(BASEC)
Maladie en cours d'investigation
Glioblastoma
(BASEC)
All individuals with newly diagnosed glioblastoma who have not yet received any treatment (except for surgical removal of the tumor) can participate. Additionally, they must be 18 years or older.
(BASEC)
Critères d'exclusion
- Previous treatment of gliomas, except for surgeries.
- Inability to undergo a contrast-enhanced MRI.
- Intention to be treated with tumor-treating fields (Tumor-treating Fields/ TTFields) before tumor progression.
(BASEC)
Lieu de l’étude
Bâle, Genève, Zurich
(BASEC)
Sponsor
Sponsor: Philogen S.p.A. Sponsor’s representative in Switzerland: Philochem AG
(BASEC)
Contact pour plus d'informations sur l'étude
Personne de contact en Suisse
Teresa Hemmerle
+41435448800
regulatory@clutterphilogen.comPhilochem AG - Libernstrasse 3 - 8112 Otelfingen
(BASEC)
Informations scientifiques
Universitatspital Zurich - Klinik fur Neurologie & Hirntumorzentrum
(ICTRP)
Nom du comité d'éthique approbateur (pour les études multicentriques, uniquement le comité principal)
Commission cantonale de Zurich
(BASEC)
Date d'approbation du comité d'éthique
30.07.2020
(BASEC)
Identifiant de l'essai ICTRP
NCT04443010 (ICTRP)
Titre officiel (approuvé par le comité d'éthique)
Eine Studie zur Beurteilung der Sicherheit und Wirksamkeit des tumorspezifischen humanen monoklonalen Antikörper-Zytokin Fusionsproteins L19TNF plus Standard-Strahlentherapie und Temozolomid bei Patienten mit neu diagnostiziertem Glioblastom (BASEC)
Titre académique
A Study to Evaluate the Safety and Efficacy of the Tumor-targeting Human Antibody-cytokine Fusion Protein L19TNF Plus Standard Temozolomide Chemoradiotherapy in Patients With Newly Diagnosed Glioblastoma (ICTRP)
Titre public
Safety and Efficacy of L19TNF Plus Temozolomide Chemoradiotherapy in Patients With Newly Diagnosed Glioblastoma (ICTRP)
Maladie en cours d'investigation
Glioblastoma
(ICTRP)
Intervention étudiée
Drug: Onfekafusp alfa
Drug: Temozolomide
(ICTRP)
Type d'essai
Interventional (ICTRP)
Plan de l'étude
Allocation: Non-Randomized. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: None (Open Label).
(ICTRP)
Critères d'inclusion/exclusion
Inclusion Criteria:
1. Male or female, age =18.
2. Patients with histologically confirmed newly diagnosed glioblastoma.
3. Karnofsky Performance Score (KPS) = 70%
4. Documented negative test for HIV-HBV-HCV. For HBV serology, the determination of HBsAg
and anti-HBcAg Ab is required. In patients with serology documenting previous exposure
to HBV (i.e., anti-HBs Ab with no history of vaccination and/or anti-HBc Ab), negative
serum HBV-DNA is required. For HCV, HCV-RNA or HCV antibody test is required. Subjects
with a positive test for HCV antibody but no detection of HCV-RNA indicating no
current infection are eligible.
5. Female patients: negative pregnancy test for women of childbearing potential (WOCBP)*
within 14 days of starting treatment. WOCBP must agree to use, from the screening to 6
months following the last study drug administration, highly effective contraception
methods, as defined by the "Recommendations for contraception and pregnancy testing in
clinical trials" issued by the Head of Medicine Agencies' Clinical Trial Facilitation
Group (www.hma.eu/ctfg.html) and which include, for instance, progesterone-only or
combined (estrogen- and progesterone-containing) hormonal contraception associated
with inhibition of ovulation, intrauterine devices, intrauterine hormone-releasing
systems, bilateral tubal occlusion or vasectomized partner.
6. Male patients: male subjects able to father children must agree to use two acceptable
methods of contraception throughout the study (e.g. condom with spermicidal gel).
Double-barrier contraception is required.
7. Personally signed and dated informed consent document indicating that the subject has
been informed of all pertinent aspects of the study.
8. Willingness and ability to comply with the scheduled visits, treatment plan,
laboratory tests and other study procedures.
- Women of childbearing potential are defined as females who have experienced menarche, are not postmenopausal (12 months with no menses without an alternative medical cause) and are not permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral oophorectomy, or bilateral salpingectomy).
Exclusion Criteria:
1. Prior treatment for glioma, except surgery.
2. Inability to undergo contrast-enhanced MRI.
3. Intent to be treated with tumor-treating fields prior to progression.
4. Known history of allergy to TNF or TMZ, any excipient in the study medication or any
other intravenously administered human proteins/peptides/antibodies.
5. Absolute neutrophil count (ANC) < 1.5 x 10^9/L, platelets < 100 x 10^9/L or
haemoglobin (Hb) < 9.0 g/dl.
6. Chronically impaired renal function as indicated by creatinine clearance < 60 mL/min
or serum creatinine > 1.5 ULN.
7. Inadequate liver function (ALT, AST, ALP = 2.5 x ULN or total bilirubin = 2.0 x ULN).
8. INR > 1.5 ULN.
9. Any severe concomitant condition which makes it undesirable for the patient to
participate in the study or which could jeopardize compliance with the protocol, in
the opinion of the investigator.
10. Active or history of autoimmune disease that might deteriorate when receiving an
immuno-stimulatory agent.
11. History within the last year of cerebrovascular disease and/or acute or subacute
coronary syndromes including myocardial infarction, unstable or severe stable angina
pectoris.
12. Heart insufficiency (> Grade II, New York Heart Association (NYHA) criteria).
13. Clinically significant cardiac arrhythmias or requiring permanent medication.
14. Abnormal LVEF or any other abnormalities observed during baseline ECG and
echocardiogram investigations that are considered as clinically significant by the
investigator. Subjects with current or a history of QT/QTc prolongation are excluded.
15. Uncontrolled hypertension.
16. Known arterial aneurism at high risk of rupture.
17. Ischemic peripheral vascular disease (Grade IIb-IV according to Leriche-Fontaine
classification).
18. Medically documented history of or active major depressive episode, bipolar disorder
(I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt
or ideation, or homicidal ideation (e.g. risk of doing harm to self or others), or
patients with active severe personality disorders.
19. Anxiety = CTCAE Grade 3.
20. Severe diabetic retinopathy such as severe non-proliferative retinopathy and
proliferative retinopathy.
21. Major trauma including major surgery (such as abdominal/cardiac/thoracic surgery)
within 3 weeks of administration of study treatment.
22. Known history of tuberculosis.
23. Pregnancy or breast feeding.
24. Requirement of chronic administration of high dose corticosteroids or other
immunosuppressant drugs. Subjects must have been either off corticosteroids, or on a
stable or decreasing dose = 4 mg daily dexamethasone (or equivalent) for 7 days prior
to start of chemoradiotherapy. Limited or occasional use of corticosteroids to treat
or prevent acute adverse reactions is not considered an exclusion criterion.
25. Presence of active and uncontrolled infections or other severe concurrent disease,
which, in the opinion of the investigator, would place the patient at undue risk or
interfere with the study.
26. Concurrent malignancies unless the patient has been disease-free without intervention
for at least 2 years.
27. Growth factors or immunomodulatory agents within 7 days prior to the administration of
study treatment.
28. Serious, non-healing wound, ulcer, or bone fracture.
29. Requirement of concurrent therapy with anticoagulants at therapeutic doses.
30. Requirement of concurrent use of other anti-cancer treatments or agents other than
study medication.
31. Any recent live vaccination within 4 weeks prior to treatment or plan to receive
vaccination during the study.
Minimum age: 18 Years
Maximum age: N/A
Sex: All
(ICTRP)
non disponible
Critères d'évaluation principaux et secondaires
For Phase 1: DLT
For Phase 2: Overall Survival
(ICTRP)
BORR in CR
BORR in PR
BORR in SD
DCR in CR
DCR in PR
DCR in SD
ORR in CR
ORR in PR
PFS
Safety (AE)
Safety (DILI)
Safety (SAE)
(ICTRP)
Date d'enregistrement
17.06.2020 (ICTRP)
Inclusion du premier participant
01.12.2020 (ICTRP)
Sponsors secondaires
non disponible
Contacts supplémentaires
Teresa Hemmerle, PhD, regulatory@philogen.com, +390577017816 (ICTRP)
ID secondaires
PH-L19TNFTMZ-01/20 (ICTRP)
Résultats-Données individuelles des participants
non disponible
Informations complémentaires sur l'essai
http://www.who.int/trialsearch/Trial2.aspx?TrialID=NCT04443010 (ICTRP)
Résultats de l'essai
Résumé des résultats
non disponible
Lien vers les résultats dans le registre primaire
non disponible