JOURNAL ONKOLOGIE – STUDIE
GLIOMOON
Tobias Weiss, MD
Principal Investigator
Universitätsspital Zürich
Teresa Hemmerle
Kontakt:
Phone: +39057717816
E-Mail: regulatory@philogen.com» Kontaktdaten anzeigen
Serena Bettarini
Kontakt:
Phone: +39057717816
E-Mail: regulatory@philogen.com» Kontaktdaten anzeigen
Studienlocations
Universitatspital Zurich - Klinik fur Neurologie & Hirntumorzentrum
CH-8091 Zürich
SwitzerlandRekrutierend» Google-Maps
Ansprechpartner:
Tobias Weiss, MD
Phone: +41 44 255 11 11» Ansprechpartner anzeigen
The purpose of this study is to explore the safety and efficacy profile of the
antibody-cytokine fusion protein L19TNF in patients with isocitrate dehydrogenase (IDH)
wildtype WHO grade III / IV glioma at first relapse
Phase I:
The primary objective of this phase is to evaluate the safety of L19TNF in patients with
IDH-wildtype WHO grade III / IV glioma at first relapse and to establish and confirm the
recommended dose (RD) for phase II.
Phase II:
The primary objective of this phase is to evaluate antitumor activity of L19TNF in patients
with IDH-wildtype WHO grade III / IV glioma at first relapse.
1. Male or female, age 18 or more
2. Patients with histologically confirmed IDH-wildtype WHO grade III / IV glioma at first
relapse
3. Radiographic demonstration of disease progression
4. Presence of at least one lesion of bi-dimensionally measurable disease by MRI of at
least 1 cm (10 mm) in the longest diameter on baseline MRI.
5. Karnofsky Performance Score (KPS) ≥ 70%
6. Documented negative test for HIV-HBV-HCV. For HBV serology: the determination of
HBsAg, anti-HBsAg-Ab 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. Subjects with a positive test for HCV antibody but no detection of
HCV-RNA indicating no current infection are eligible.
7. 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
six 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, progesteron-only or combined (estrogen- and progesteron-containing) hormonal
contraception associated with inhibition of ovulation, intrauterine devices,
intrauterine hormone-releasing systems, bilateral tubal occlusion or vasectomized
partner.
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.
8. Negative TB test (e.g. Mantoux or Quantiferon assay).
9. Evidence of a personally signed and dated informed consent document indicating that
the subject has been informed of all pertinent aspects of the study.
10. 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. Second or later glioma progression.
2. Surgical resection or biopsy of glioma within 4 weeks of the start of study treatment.
3. Subjects who participated in an investigational drug or device study within 4 weeks
prior to study treatment start.
4. Treatment with tumor-treating fields
5. Radiotherapy within 6 weeks prior to study treatment start.
6. Patients unable to undergo contrast-enhanced MRI.
7. Patient taking herbal medications within 7 days prior to first dose of the study drug.
8. Known history of allergy to TNF, excipient in study medication or any other
intravenously administered human proteins/peptides/antibodies.
9. Absolute neutrophil count (ANC) < 1.5 x 10^9/L, platelets < 100 x 10^9/L or
haemoglobin (Hb) < 9.0 g/dl.
10. Chronically impaired renal function as indicated by creatinine clearance < 60 mL/min.
11. Inadequate liver function (ALT, AST, ALP ≥ 2.5 x ULN or total bilirubin ≥ 2.0 x ULN)
12. 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.
13. History within the last year of cerebrovascular disease and/or acute or subacute
coronary syndromes including myocardial infarction, unstable or severe stable angina
pectoris.
14. Heart insufficiency (> Grade II, New York Heart Association (NYHA) criteria).
15. Clinically significant cardiac arrhythmias or requiring permanent medication.
16. Abnormal LVEF or any other abnormalities observed during baseline ECG and
echocardiogram investigations that are considered as clinically significant by the
investigator.
17. Uncontrolled hypertension.
18. Ischemic peripheral vascular disease (Grade IIb-IV according to Leriche-Fontaine
classification).
19. 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.
20. Anxiety ≥ CTCAE grade 3
21. Severe diabetic retinopathy such as severe non-proliferative retinopathy and
proliferative retinopathy.
22. Major trauma including major surgery (such as abdominal/cardiac/thoracic surgery)
within 4 weeks of administration of study treatment.
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 ≤ 10 mg daily prednisone (or equivalent) for at least 2
weeks prior to study treatment start. 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 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.
1. Occurrence of Dose Limiting Toxicity (DLT) (Time Frame - From the first day of treatment until the end of the DLT window (up to 21 days))
2. Adverse event (AE), Serious Adverse Events (SAE) and Drug Induced Liver Injury (DILI) assessment based on CTCAE v.5.0 (Time Frame - From the inclusion in the study (signature of the informed consent form - ICF) until the end of follow-up (up to approximately 36 months))
3. Standard laboratory (haematology, biochemistry, liver and urine analysis) parameters (Time Frame - From the inclusion in the study (signature of the informed consent form - ICF) until the end of follow-up (up to approximately 36 months))
4. Neurological assessment using the Neurologic assessment in Neuro-Oncology (NANO) scale (Time Frame - From the inclusion in the study (signature of the informed consent form - ICF) until the end of follow-up (up to approximately 36 months)):
Measurement of neurological function in neuro-oncology
5. Karnofsky Performance Status (Time Frame - From the inclusion in the study (signature of the informed consent form - ICF) until the end of follow-up (up to approximately 36 months)):
Assessment through a questionnaire of symptom-related restriction of activity, self-sufficiency and self-determination
6. Electrocardiogram (ECG) findings. In particular, data about QT/QTc intervals will be collected and analysed for QT/QTc prolongation potentially caused by treatment. (Time Frame - From the inclusion in the study (signature of the informed consent form - ICF) until the end of follow-up (up to approximately 36 months))
7. Echocardiogram (ECHO) findings. In particular, data about QT/QTc intervals will be collected and analysed for QT/QTc prolongation potentially caused by treatment. (Time Frame - From the inclusion in the study (signature of the informed consent form - ICF) until the end of follow-up (up to approximately 36 months))
8. Assessment of the formation of human anti-fusion protein antibodies (HAFA) against L19TNF. (Time Frame - Cycle 1 day 1 - First Follow Up visit (up to approximately 9 months))
9. Progression-free survival (PFS), according to iRANO (immunotherapy response assessment in neuro-oncology) criteria based on standardized MRI protocol (Time Frame - At 6 months)
Secondary outcome:
1. Progression free survival (PFS) (Time Frame - From the inclusion in the study (signature of the informed consent form - ICF) until the end of follow-up (up to approximately 12 months))
2. Overall survival (OS). (Time Frame - From the inclusion in the study (signature of the informed consent form - ICF) until the end of follow-up (up to approximately 36 months))
3. Overall Response Rate (ORR, consisting of Complete and partial Response), based on iRANO criteria. (Time Frame - At 12 weeks, 24 weeks, 36 weeks, 48 weeks)
Safety and Efficacy of L19TNF in Patients With Isocitrate Dehydrogenase (IDH) Wildtype WHO Grade III / IV Glioma at First Relapse
Rekrutierend
NCT-Nummer:
NCT03779230
Studienbeginn:
Mai 2019
Letztes Update:
25.01.2021
Wirkstoff:
L19TNF
Indikation (Clinical Trials):
Glioma
Geschlecht:
Alle
Altersgruppe:
Erwachsene (18+)
Phase:
-
Sponsor:
Philogen S.p.A.
Collaborator:
-
Studienleiter
Principal Investigator
Universitätsspital Zürich
Kontakt
Kontakt:
Phone: +39057717816
E-Mail: regulatory@philogen.com» Kontaktdaten anzeigen
Kontakt:
Phone: +39057717816
E-Mail: regulatory@philogen.com» Kontaktdaten anzeigen
Studienlocations
(1 von 1)
CH-8091 Zürich
SwitzerlandRekrutierend» Google-Maps
Ansprechpartner:
Tobias Weiss, MD
Phone: +41 44 255 11 11» Ansprechpartner anzeigen
Studien-Informationen
Detailed Description:The purpose of this study is to explore the safety and efficacy profile of the
antibody-cytokine fusion protein L19TNF in patients with isocitrate dehydrogenase (IDH)
wildtype WHO grade III / IV glioma at first relapse
Phase I:
The primary objective of this phase is to evaluate the safety of L19TNF in patients with
IDH-wildtype WHO grade III / IV glioma at first relapse and to establish and confirm the
recommended dose (RD) for phase II.
Phase II:
The primary objective of this phase is to evaluate antitumor activity of L19TNF in patients
with IDH-wildtype WHO grade III / IV glioma at first relapse.
Ein-/Ausschlusskriterien
Inclusion Criteria:1. Male or female, age 18 or more
2. Patients with histologically confirmed IDH-wildtype WHO grade III / IV glioma at first
relapse
3. Radiographic demonstration of disease progression
4. Presence of at least one lesion of bi-dimensionally measurable disease by MRI of at
least 1 cm (10 mm) in the longest diameter on baseline MRI.
5. Karnofsky Performance Score (KPS) ≥ 70%
6. Documented negative test for HIV-HBV-HCV. For HBV serology: the determination of
HBsAg, anti-HBsAg-Ab 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. Subjects with a positive test for HCV antibody but no detection of
HCV-RNA indicating no current infection are eligible.
7. 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
six 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, progesteron-only or combined (estrogen- and progesteron-containing) hormonal
contraception associated with inhibition of ovulation, intrauterine devices,
intrauterine hormone-releasing systems, bilateral tubal occlusion or vasectomized
partner.
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.
8. Negative TB test (e.g. Mantoux or Quantiferon assay).
9. Evidence of a personally signed and dated informed consent document indicating that
the subject has been informed of all pertinent aspects of the study.
10. 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. Second or later glioma progression.
2. Surgical resection or biopsy of glioma within 4 weeks of the start of study treatment.
3. Subjects who participated in an investigational drug or device study within 4 weeks
prior to study treatment start.
4. Treatment with tumor-treating fields
5. Radiotherapy within 6 weeks prior to study treatment start.
6. Patients unable to undergo contrast-enhanced MRI.
7. Patient taking herbal medications within 7 days prior to first dose of the study drug.
8. Known history of allergy to TNF, excipient in study medication or any other
intravenously administered human proteins/peptides/antibodies.
9. Absolute neutrophil count (ANC) < 1.5 x 10^9/L, platelets < 100 x 10^9/L or
haemoglobin (Hb) < 9.0 g/dl.
10. Chronically impaired renal function as indicated by creatinine clearance < 60 mL/min.
11. Inadequate liver function (ALT, AST, ALP ≥ 2.5 x ULN or total bilirubin ≥ 2.0 x ULN)
12. 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.
13. History within the last year of cerebrovascular disease and/or acute or subacute
coronary syndromes including myocardial infarction, unstable or severe stable angina
pectoris.
14. Heart insufficiency (> Grade II, New York Heart Association (NYHA) criteria).
15. Clinically significant cardiac arrhythmias or requiring permanent medication.
16. Abnormal LVEF or any other abnormalities observed during baseline ECG and
echocardiogram investigations that are considered as clinically significant by the
investigator.
17. Uncontrolled hypertension.
18. Ischemic peripheral vascular disease (Grade IIb-IV according to Leriche-Fontaine
classification).
19. 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.
20. Anxiety ≥ CTCAE grade 3
21. Severe diabetic retinopathy such as severe non-proliferative retinopathy and
proliferative retinopathy.
22. Major trauma including major surgery (such as abdominal/cardiac/thoracic surgery)
within 4 weeks of administration of study treatment.
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 ≤ 10 mg daily prednisone (or equivalent) for at least 2
weeks prior to study treatment start. 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 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.
Studien-Rationale
Primary outcome:1. Occurrence of Dose Limiting Toxicity (DLT) (Time Frame - From the first day of treatment until the end of the DLT window (up to 21 days))
2. Adverse event (AE), Serious Adverse Events (SAE) and Drug Induced Liver Injury (DILI) assessment based on CTCAE v.5.0 (Time Frame - From the inclusion in the study (signature of the informed consent form - ICF) until the end of follow-up (up to approximately 36 months))
3. Standard laboratory (haematology, biochemistry, liver and urine analysis) parameters (Time Frame - From the inclusion in the study (signature of the informed consent form - ICF) until the end of follow-up (up to approximately 36 months))
4. Neurological assessment using the Neurologic assessment in Neuro-Oncology (NANO) scale (Time Frame - From the inclusion in the study (signature of the informed consent form - ICF) until the end of follow-up (up to approximately 36 months)):
Measurement of neurological function in neuro-oncology
5. Karnofsky Performance Status (Time Frame - From the inclusion in the study (signature of the informed consent form - ICF) until the end of follow-up (up to approximately 36 months)):
Assessment through a questionnaire of symptom-related restriction of activity, self-sufficiency and self-determination
6. Electrocardiogram (ECG) findings. In particular, data about QT/QTc intervals will be collected and analysed for QT/QTc prolongation potentially caused by treatment. (Time Frame - From the inclusion in the study (signature of the informed consent form - ICF) until the end of follow-up (up to approximately 36 months))
7. Echocardiogram (ECHO) findings. In particular, data about QT/QTc intervals will be collected and analysed for QT/QTc prolongation potentially caused by treatment. (Time Frame - From the inclusion in the study (signature of the informed consent form - ICF) until the end of follow-up (up to approximately 36 months))
8. Assessment of the formation of human anti-fusion protein antibodies (HAFA) against L19TNF. (Time Frame - Cycle 1 day 1 - First Follow Up visit (up to approximately 9 months))
9. Progression-free survival (PFS), according to iRANO (immunotherapy response assessment in neuro-oncology) criteria based on standardized MRI protocol (Time Frame - At 6 months)
Secondary outcome:
1. Progression free survival (PFS) (Time Frame - From the inclusion in the study (signature of the informed consent form - ICF) until the end of follow-up (up to approximately 12 months))
2. Overall survival (OS). (Time Frame - From the inclusion in the study (signature of the informed consent form - ICF) until the end of follow-up (up to approximately 36 months))
3. Overall Response Rate (ORR, consisting of Complete and partial Response), based on iRANO criteria. (Time Frame - At 12 weeks, 24 weeks, 36 weeks, 48 weeks)
Geprüfte Regime
- L19TNF (onfekafusp alpha):
Patients will be assigned to the following increasing dose levels of L19TNF: 10 and 13 μg/kg.
Quelle: ClinicalTrials.gov
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