L19TNF + Lomustine for Glioblastoma
(GLIOSTELLA Trial)
Recruiting in Palo Alto (17 mi)
+7 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Philogen S.p.A.
Must not be taking: Anticoagulants, Immunosuppressants
Disqualifiers: Autoimmune disease, Heart disease, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?The trial aims to collect safety, efficacy, exposure, dose- response, pharmacokinetic and pharmacodynamic information of the combination of L19TNF and lomustine at different dose levels in patients with Glioblastoma at progression or recurrence
Will I have to stop taking my current medications?
The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have had anti-cancer treatments, certain investigational drugs, or specific medications like high-dose corticosteroids within a certain period before starting the trial. It's best to discuss your current medications with the trial team.
What data supports the effectiveness of the drug L19TNF + Lomustine for Glioblastoma?
Research shows that lomustine, a component of the treatment, is effective in treating high-grade gliomas and glioblastoma, especially when combined with other drugs like temozolomide, as it improved overall survival in certain trials. However, the effectiveness of L19TNF specifically for glioblastoma is not directly addressed in the available research.
12345Is the combination of L19TNF and Lomustine safe for humans?
Lomustine, a part of the treatment, can cause lung issues like pulmonary fibrosis (scarring of lung tissue) and hematotoxicity (blood-related side effects). These side effects have been observed in treatments for brain tumors, indicating potential safety concerns.
45678What makes the drug L19TNF + Lomustine unique for treating glioblastoma?
The combination of L19TNF and Lomustine is unique because it pairs a targeted therapy (L19TNF) with a chemotherapy agent (Lomustine), potentially enhancing the treatment's effectiveness against glioblastoma by targeting tumor blood vessels and cancer cells simultaneously. This approach differs from standard treatments that typically involve surgery, radiation, and temozolomide chemotherapy.
145910Eligibility Criteria
This trial is for adults over 18 with confirmed glioblastoma that has progressed or recurred. They must have a Karnofsky Performance Status of at least 60%, known MGMT promoter status, and no HIV, HBV, or HCV infections. Women must not be able to bear children or use effective contraception; men also need to agree to use contraception.Inclusion Criteria
My glioblastoma diagnosis is confirmed and has progressed.
I know my cancer's MGMT promoter status.
I am 18 years old or older.
+7 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive L19TNF and lomustine in a 42-day cycle for up to 6 cycles
36 weeks
6 cycles with multiple visits per cycle
Follow-up
Participants are monitored for safety and effectiveness after treatment
12 months
Participant Groups
The study tests the combination of L19TNF and lomustine in various doses on patients with recurrent or progressing glioblastoma. It aims to assess safety, effectiveness, how the body processes the drugs (pharmacokinetics), and their impact on the disease (pharmacodynamics).
6Treatment groups
Experimental Treatment
Group I: Arm FExperimental Treatment2 Interventions
Patients will be treated with L19TNF on Days 1, 3 and 5, and on Days 22, 24 and 26 and Lomustine on Day 1 (in the evening after L19TNF infusion) of a 42-day cycle for up to a maximum of 6 cycles.
Group II: Arm EExperimental Treatment2 Interventions
Patients will be treated with L19TNF on Days 1, 3 and 5, and on Days 22, 24 and 26 and Lomustine on Day 1 (in the evening after L19TNF infusion) of a 42-day cycle for up to a maximum of 6 cycles.
Group III: Arm DExperimental Treatment2 Interventions
Patients will be treated with L19TNF on Days 1, 3 and 5, and on Days 22, 24 and 26 and Lomustine on Day 1 (in the evening after L19TNF infusion) of a 42-day cycle for up to a maximum of 6 cycles.
Group IV: Arm CExperimental Treatment2 Interventions
Patients will be treated with L19TNF on Days 1, 3 and 5, and on Days 22, 24 and 26 and Lomustine on Day 1 (in the evening after L19TNF infusion) of a 42-day cycle for up to a maximum of 6 cycles.
Group V: Arm BExperimental Treatment2 Interventions
Patients will be treated with on Days 1, 3 and 5, and on Days 22, 24 and 26 and Lomustine on Day 1 (in the evening after L19TNF infusion) of a 42-day cycle for up to a maximum of 6 cycles
Group VI: Arm AExperimental Treatment2 Interventions
Patients will be treated with L19TNF on Days 1, 3 and 5, and on Days 22, 24 and 26 and Lomustine on Day 1 (in the evening after L19TNF infusion) of a 42-day cycle for up to a maximum of 6 cycles.
L19TNF is already approved in European Union for the following indications:
🇪🇺 Approved in European Union as Onfekafusp alfa for:
- Soft tissue sarcoma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Northwestern Memorial HospitalChicago, IL
Massachusetts General Hospital (MGH)Boston, MA
Beth Israel Deaconess Medical Center (BIDMC)Boston, MA
Dana-Farber Cancer Institute (DFCI)Boston, MA
More Trial Locations
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Who Is Running the Clinical Trial?
Philogen S.p.A.Lead Sponsor
References
Nitrosoureas in the Management of Malignant Gliomas. [2018]Nitrosoureas represent one of the most active classes of agents in the treatment of high-grade gliomas and glioblastoma. In clinical practice, the most commonly used compounds are lomustine (either alone or in combination with procarbazine and vincristine), carmustine, and fotemustine. Given their toxicity profile and subsequent to the introduction of temozolomide in clinical practice, most of these agents were moved to the recurrent setting. This review focuses on the role of the nitrosoureas currently used in clinical practice for the treatment of malignant gliomas.
Undetected pseudoprogressions in the CeTeG/NOA-09 trial: hints from postprogression survival and MRI analyses. [2023]In the randomized CeTeG/NOA-09 trial, lomustine/temozolomide (CCNU/TMZ) was superior to TMZ therapy regarding overall survival (OS) in MGMT promotor-methylated glioblastoma. Progression-free survival (PFS) and pseudoprogression rates (about 10%) were similar in both arms. Further evaluating this discrepancy, we analyzed patterns of postprogression survival (PPS) and MRI features at first progression according to modified RANO criteria (mRANO).
Fotemustine: a third-generation nitrosourea for the treatment of recurrent malignant gliomas. [2021]Malignant gliomas account for approximately 60% of all primary brain tumors in adults. The prognosis for patients with malignant glioma has not changed significantly in recent years. Despite debulking surgery, radiotherapy and cytotoxic chemotherapy, the median survival time is nine to 12 months, and very few, if any, patients are cured from this illness. Fotemustine is an alkylating agent characterized by the grafting of a phosphonoalanine group onto the nitrosourea radical with consequent high lipophilicity and improved diffusion through the cell membrane and the blood-brain barrier. Fotemustine has been registered for use in two indications: disseminated malignant melanoma, including cerebral metastases, and primary brain tumors. Fotemustine is currently used in Europe, particularly in France and Italy, as a salvage therapy for recurrent malignant gliomas. Myelosuppression, leucopenia and thrombocytopenia are the most frequent side effects of treatment with fotemustine. The objective response to this treatment is between 26% and 70%, and the reported median survival time is 10 months. New drug combinations containing fotemustine and angiogenesis inhibitors, such as bevacizumab, are currently under development. In this review, we describe all the combinations of fotemustine currently used in clinical practice for recurrent malignant gliomas.
Patterns, predictors and prognostic relevance of high-grade hematotoxicity after temozolomide or temozolomide-lomustine in the CeTeG/NOA-09 trial. [2023]In the randomized phase III trial CeTeG/NOA-09, temozolomide (TMZ)/lomustine (CCNU) combination therapy was superior to TMZ in newly diagnosed MGMT methylated glioblastoma, albeit reporting more frequent hematotoxicity. Here, we analyze high grade hematotoxicity and its prognostic relevance in the trial population.
The Efficacy and Safety of Adjuvant Lomustine to Chemotherapy for Recurrent Glioblastoma: A Meta-analysis of Randomized Controlled Studies. [2022]Lomustine is regarded as 1 common anti-vascular endothelial growth factor agent. The efficacy of adjuvant lomustine to chemotherapy remains controversial for recurrent glioblastoma. We conduct this meta-analysis to explore the influence of adjuvant lomustine on treatment efficacy of recurrent glioblastoma.
[A multicenter randomized controlled study of temozolomide in 97 patients with malignant brain glioma]. [2018]To investigate the efficacy and safety of temozolomide (TMZ) and lomustine (CCNU) in malignant brain gliomas.
Restrictive lung disease following treatment for malignant brain tumors: a potential late effect of craniospinal irradiation. [2017]To examine the effects of lomustine (CCNU), a commonly used nitrosourea, and craniospinal radiation therapy on the subsequent development of restrictive lung disease (RLD) following treatment for malignant brain tumors.
Lung toxicity of lomustine in the treatment of progressive gliomas. [2022]Pulmonary fibrosis is a rare, but dangerous side effect of CCNU (lomustine). CCNU is a frequently used chemotherapeutic agent in the setting of recurrent or progressive glioblastoma. At present, CCNU is also administered in patients with newly diagnosed gliomas in combination with temozolomide. There is only little evidence if, and how, lung function should be monitored on treatment with CCNU.
How did lomustine become standard of care in recurrent glioblastoma? [2020]Glioblastomas are the most common malignant primary intrinsic brain tumors. Their incidence increases with age, and males are more often affected. First-line management includes maximum safe surgical resection followed by involved-field radiotherapy plus concomitant and six cycles of maintenance temozolomide chemotherapy. Standards of care at recurrence are much less well defined. Minorities of patients are offered second surgery or re-irradiation, but data on a positive impact on survival from randomized trials are lacking. The majority of patients who are eligible for salvage therapy receive systemic treatment, mostly with nitrosourea-based regimens or, depending on availability, bevacizumab alone or in various combinations. In clinical trials, lomustine alone has been increasingly used as a control arm, assigning this drug a standard-of-care position in the setting of recurrent glioblastoma. Here we review the activity of lomustine in the treatment of diffuse gliomas of adulthood in various settings. The most compelling data for lomustine stem from three randomized trials when lomustine was combined with procarbazine and vincristine as the PCV regimen in the newly diagnosed setting together with radiotherapy; improved survival with PCV was restricted to patients with isocitrate dehydrogenase-mutant tumors. No other agent with the possible exception of regorafenib has shown superior activity to lomustine in recurrent glioblastoma, but activity is largely restricted to patients with tumors with O6-methylguanine DNA methyltransferase (MGMT) promoter methylation. Hematological toxicity, notably thrombocytopenia often limits adequate exposure.
Palliative therapy of melanoma patients with fotemustine. Inverse relationship between tumour load and treatment effectiveness. A multicentre phase II trial of the EORTC-Melanoma Cooperative Group (MCG). [2019]Fotemustine (FM) is a new chloronitrosurea (CNU), chemically characterized by the graft of an aminophosphonic acid on the CNU radical, which makes it highly lipophilic. Following single-institution phase I and II studies with remarkably high response rates of some 40%, including brain metastases of 25% and more, the EORTC-MCG started a multicentre phase II trial to confirm these results according to EORTC guidelines. Treatment consisted of an induction cycle of FM (100 mg/m2 on days 1 + 8 + 15), followed by maintenance courses (q3w). Fifty-four patients were entered by 11 institutions. General interest in this promising new agent, however, led clinicians of six additional institutions to join the EORTC trial and 90 more patients were included in only 4 months. This rapidly rising accrual rate became inversely related to the physicians' adherence to the eligibility criteria: palliation of symptoms rather than clinical research was the dominant reason to start treatment. Clinical characteristics and results in the eligible vs non-eligible patient group (in parentheses) were as follows: male/female 29/26 (68/65), mean age 54 years (53), ECOG-PS 0-1 (0-4), CR 2 (0), PR 10 (2), NC 17 (5) and for brain metastases: PR 4 (1), NC 2 (1), for an ORR of 12% (5%). Median duration of response was 6 months (range 4-16). The clinically relevant toxicity was limited to the haematopoiesis with delayed platelet nadirs (30% grade III+IV), granulocyte (25% grade III + IV) and the gastrointestinal tract: nausea and vomiting (26% grade II, 18% III, 1% IV). This study confirms that FM is active in melanoma including brain metastases.(ABSTRACT TRUNCATED AT 250 WORDS)