Improvement of functional Outcome for patients with newly diagnosed grade 2 or 3 glioma

Phase 1

• Conditions: WHO grade 2 or 3 glioma; MedDRA version: 20.0Level: PTClassification code 10018338Term: GliomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.1Level: LLTClassification code 10030288Term: Oligodendroglioma malignantSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-005027-16-DE
• Lead Sponsor: Heidelberg University Hospital Represented in law by its Commercial Managing Director

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2020-05-15
• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 406

Inclusion Criteria

1.Histologically confirmed, newly diagnosed CNS WHO grade 2 or 3 glioma.
2.Tumor carries an isocitrate dehydrogenase (IDH) mutation (determined by immunohistochemistry (IHC) and/or deoxyribonucleic acid (DNA) sequencing).
3.Tumor is co-deleted for 1p/19q (determined by copy number variations, fluorescence in situ hybridization (FISH), multiplex ligation-dependent probe amplification (MLPA) or other appropriate methods).
4.Biopsy (with sufficient tissue for molecular pathology) or resection
5.Age: ?18 years.
6.Karnofsky Permormance status (KPS) =60%.
7.Life expectancy > 6 months.
8.Availability of formalin-fixed paraffin-embedded (FFPE) or fresh-frozen tissue and ethylenediamine tetraacetic acid (EDTA) blood for biomarker research.
9.Standard magnetic resonance imaging (MRI) = 72 h post-surgery according to the present national and international guidelines.
10.Craniotomy or intracranial biopsy site must be adequately healed.
11.= 2 weeks and = 3 months from surgery without any interim radio- or chemotherapy or experimental intervention.
12.Willing and able to comply with regular neurocognitive and health-related quality of life tests/questionnaires.
13.Indication for postsurgical cytostatic/-toxic therapy.
14.Written Informed consent.
15.Female patients with reproductive potential have a negative pregnancy test (serum or urine) within 6 days prior to start of therapy. Female patients are surgically sterile or agree to use adequate contraception during the period of therapy and 6 months after the end of study treatment, or women have been postmenopausal for at least 2 years.1
16.Male patients are willing to use contraception.2

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 406
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Main Exclusion Criteria:
1. Participation in other ongoing interventional clinical trials.
2. Inability to undergo MRI.
3. Abnormal (= Grade 2 CTCAE v5.0 laboratory values for hematology (Hb, WBC, neutrophils, or platelets), liver (serum bilirubin, ALT, or AST) or renal function (serum creatinine).
4. Clinically active tuberculosis; known HIV infection or active Hepatitis B (HBV) or Hepatitis C (HCV infection, or active infections requiring oral or intravenous antibiotics or that can cause a severe disease and pose a severe danger to lab personnel working on patients’ blood or tissue (e.g. rabies).
5. Any prior anti-cancer therapy or co-administration of anti-cancer therapies other than those administered/allowed in this study. History of low-grade glioma that did not require prior treatment with chemotherapy or radiotherapy is not an exclusion criterion.
6. Immunosuppression, not related to prior treatment for malignancy.
7. History of other malignancies (except for adequately treated basal or squamous cell carcinoma or carcinoma in situ) within the last 5 years unless the patient has been disease-free for 5 years.
8. Any clinically significant concomitant disease (including hereditary fructose intolerance) or condition that could interfere with, or for which the treatment might interfere with, the conduct of the study or the absorption of oral medications or that would, in the opinion of the Principal Investigator, pose an unacceptable risk to the patient in this study.
9. Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol requirements and/or follow-up procedures; those conditions should be discussed with the patient before trial entry.
10. Pregnancy or breastfeeding.
11. History of hypersensitivity to the investigational medicinal product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product.
12. QTc time prolongation > 500 ms.
13. Patients under restricted medication for procarbazine, lomustine, vincristine and temozolomide (see list of restricted medication in Appendix A)
14.Liver disease characterized by:
a.ALT or AST (= Grade 2 CTCAE v5.0) confirmed on two consecutive measurements
OR
b.Impaired excretory function (e.g., hyperbilirubinemia) or synthetic function or other conditions of decompensated liver disease such as coagulopathy, hepatic encephalopathy, hypoalbuminemia, ascites, and bleeding from esophageal varices (= Grade 2 CTCAE v5.0)
OR
c.Acute viral or active autoimmune, alcoholic, or other types of acute hepatitis
15.Known uncorrected coagulopathy, platelet disorder, or history of non-drug induced thrombocytopenia.
16.History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener’s granulomatosis, Sjögren’s syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis; autoimmune-related hypothyroidism (patients on a stable dose of thyroid replacement hormone are eligible for this study) and type I diabetes mellitus (patients on a stable dose of insulin regimen are eligible for this study).
17.Vaccination with life vaccines during treatment and 4 weeks before start of treatment.
18.Existing neuromuscular diseases, especially neu

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified