2-OHOA With RT and TMZ for Adults With Glioblastoma

• Status: Recruiting
• Trial end date: 2023-10-30
• Target enrollment: 0
• Participant gender: All

Summary

The proposed Phase IIB/III randomized, double-blind, placebo-controlled trial in subjects with newly diagnosed primary glioblastoma multiforme (ndGBM) aims to compare the efficacy and safety of 2-OHOA versus placebo, given with standard of care (SoC) therapy of radiation therapy plus temozolomide (TMZ), followed by an adjuvant treatment of 6 month period of TMZ and then 2-OHOA or placebo in monotherapy.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Laminar Pharmaceuticals; Lipopharma Therapeutics SL
• Collaborators: Covance; LIPODOM THERAPEUTICS; Northern Institute for Cancer Research, Newcastle; SEQUENCING MULTIPLEX; Specialized Medical Services (SMS)-Oncology BV; Theradis; Theradis pharma

Criteria

Inclusion criteria:

1. Written informed consent, signed and dated

2. Subjects who are able to understand and follow instructions during the trial

3. Age ≥18 and ≤75

4. Subjects with newly histologically confirmed intracranial malignant glioma (glioblastoma WHO Grade IV) that is IDH1 wildtype (local assessment) and who are scheduled to receive chemo-radiotherapy with temozolomide

5. Ability to swallow and retain oral medication

6. Centrally obtained MGMT promoter methylation status

7. Subjects who underwent total or partial / incomplete resection and with the appropriate quantity of tumour tissue releasable for eligibility and signature assessments

8. Karnofsky Performance Score (KPS) > 50 %

9. Female subjects with a childbearing potential must have a negative pregnancy test within one week before inclusion in the trial. Those female and male subjects admitted in the study must use a reliable method of contraception, for female subjects during the study period up until 32 days after last study treatment and for male subjects up until 92 days after last study administration.

Women must be:

• Either of NOT childbearing potential: postmenopausal (≥ 60 years of age, or < 60 years of age and amenorrhoea for 12 months in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression with follicle-stimulating hormone (FSH) above 40 U/L and oestradiol below 30 ng/L, or if taking tamoxifen or toremifene, and age < 60 years, then FSH and oestradiol in the postmenopausal range), permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy), or otherwise incapable of pregnancy

• Or of childbearing potential and practicing a highly effective method of birth control consistent with local regulations regarding the use of birth control methods for subjects participating in clinical studies: e.g., established use of oral, injected or implanted hormonal methods of contraception; placement of an intrauterine device or intrauterine system; male partner sterilization (the vasectomized partner should be the sole partner for that subject).

10. A man who is sexually active and has not had a vasectomy must agree to use a barrier method of birth control e.g., either condom or partner with occlusive cap (diaphragm or cervical/vault caps).

11. Adequate bone marrow function including: Absolute neutrophil count (ANC) ≥1,500/mm^3 or ≥1.5 x 10^9/L; Platelets ≥ 100,000/mm3 or ≥100 x10^9/L; Haemoglobin ≥ 9 g/dL (may have been transfused).

12. Adequate hepatic function defined by a total bilirubin level ≤ 1.5 × the upper limit of normal range (ULN), an aspartate aminotransferase (AST), level ≤ 2.5 × ULN, and an alanine aminotransferase (ALT) level ≤ 2.5 × ULN or, for subjects with documented metastatic disease to the liver, AST and ALT levels ≤ 5 × ULN. Subjects with documented Gilbert disease are allowed if total bilirubin ≤ 3 x ULN

13. Adequate renal function defined by an estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula

Exclusion Criteria:

1. Known hypersensitivity to any component of the investigational product.

2. Any other investigational drug within the preceding 30 days. Prior, concomitant, or planned concomitant treatment with anti-neoplastic aim including (but not limited) to NovoTumor Treatment Fields (Novo TTF), bevacizumab, intratumoural or intracavitary anti-neoplastic therapy (e.g Gliadel wafers), or other experimental therapeutics intended to treat the tumour.

3. Subjects who underwent "only biopsy" resection

4. Anticancer therapy within 4 weeks of study entry (6 weeks for mitomycin and nitrosoureas)

5. Other major surgery within the preceding 30 days

6. Allergy, hypersensitivity or other intolerability to temozolomide and its excipients, patients with hypersensitivity to dacarbazine and patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.

7. Unable to undergo MRI

8. Presenting with diffuse midline gliomas or multifocal GBM (distant from the flare or contralateral) or rapid progression between early post-surgery MRI and pre-radiotherapy MRI

9. Uncontrolled or significant cardiovascular disease

10. A history of uncontrolled hyperlipidaemia and/or the need for concurrent lipid lowering therapy

11. Need for warfarin, phenytoin or sulphonylureas (glibenclamide, glimepiride, glipizide, glyburide or nateglanide)

12. Past medical history of uncontrolled clinically significant active or chronic gastrointestinal disorders (for example, Crohn's disease, celiac disease, untreated stomach ulcers, etc) and gastro-inflammatory pathologies

13. Uncontrolled diabetes mellitus, with glycated haemoglobin (HbA1c) levels at the screening visit of ≥7.5%

14. Cardiac disease, defined specifically as either

1. Mean resting corrected QT interval (QTc) > 470 msec (for women) and > 450 ms (for men) obtained from 3 consecutive ECGs

2. Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (example, complete left bundle branch block, third degree heart block)

3. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, potential for Torsades de Pointes, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age

15. Previous malignancies within the last three years other than ndGBM, except successfully treated squamous cell carcinoma of the skin, superficial bladder cancer, and in situ carcinoma of the cervix.