Exploring a new treatment for newly diagnosed glioblastoma

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

This study is testing a new treatment that combines L19TNF with standard chemotherapy for people who have just been diagnosed with glioblastoma to see if it works better than the usual treatment alone.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 226 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Philogen S.p.A. (Industry-sponsored)
• Locations: 1 site (Zurich)
• Trial ID: NCT04443010 on ClinicalTrials.gov

What this trial studies

This study investigates the safety and efficacy of L19TNF, an antibody-cytokine fusion protein, in combination with standard temozolomide chemoradiotherapy for patients with newly diagnosed glioblastoma. It consists of three parts: a dose-finding phase to establish the recommended dose of L19TNF, a signal-seeking phase to identify initial signs of effectiveness, and an evaluation phase to compare the efficacy of the combination treatment against standard chemoradiotherapy alone. The goal is to improve treatment outcomes for this aggressive brain cancer.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with histologically confirmed newly diagnosed glioblastoma and a Karnofsky Performance Score of 70% or higher.

Not a fit: Patients with recurrent glioblastoma or those with a Karnofsky Performance Score below 70% may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a more effective option for patients with glioblastoma, potentially improving survival rates.

How similar studies have performed: While this approach is novel, similar studies exploring combination therapies for glioblastoma have shown promise in the past.

Eligibility criteria

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.

Where this trial is running

Zurich

• UniversitatSpital USZ — Zurich, Switzerland (Recruiting)

Study contacts

• Principal investigator: Tobias Weiss, PhD, MD — Universitatspital Zurich - Klinik fur Neurologie & Hirntumorzentrum
• Study coordinator: Teresa Hemmerle, PhD

Conditions Glioblastoma