Repurposed Drugs in Research for Cancer Clinical Trials- Pitavastatin (ReDiReCCT-Pita)

C.Dirven

Status and phase: Completed; Early Phase 1

Conditions: Glioblastoma Multiforme, Adult; Recurrent Glioblastoma

Treatments: Drug: Pitavastatin calcium

Study type: Interventional

Funder types: Other

Identifiers

NCT05977738

2023-505743-38-00

UTN U1111-1294-4392 (Other Identifier)

Details and patient eligibility

About

The goal of this Phase 0 trial is to study if pre-operative oral pitavastatin administration reaches the tumour in patients with primary or a recurrent glioblastoma. The main question[s] it aims to answer are:

• Does pitavastatin reach a cytotoxic concentration in gadolinium-enhanced tumour tissue after oral administration?
• Does pitavastatin achieve a concentration that can synergize with temozolomide in the gadolinium non-enhanced area of the tumour?

Participants will receive pitavastatin in differing dosages a week before their elective surgery and blood and tumour samples will be collected.

Enrollment: 12 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Eligible for resection of a suspected primary glioblastoma or a recurrent glioblastoma.
2. MRI- measurable disease preoperatively, defined as at least 1 contrast-enhancing lesion, with 1 perpendicular measurement of at least 0.5 cm.
3. Adequate Renal Function defined as: estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 by Chronic Disease Epidemiology Collaboration (CKD-EPI) equation.
4. CK elevation 3 X ULN.
5. Ability to understand and the willingness to sign a written informed consent document.
6. Participant has voluntarily agreed to participate by giving written informed consent Written informed consent for participation in the protocol must be obtained prior to any screening procedures taking place.
7. Willingness and ability to comply with all scheduled visits, treatment plans, laboratory tests and other procedures.
8. Age ≥18 years at time of consent.
9. Ability and willingness to swallow oral medication.
10. Confirmed negative serum pregnancy test (β-hCG) before starting study treatment or participant who is no longer of childbearing potential due to surgical, chemical, or natural menopause.
11. For females of reproductive potential: use of highly effective contraception method defined as one that results in a low failure rate (ie, less than 1% per year) when used consistently and correctly.
12. Females of child-bearing potential must agree not to breastfeed starting at screening, and throughout the study period.

Exclusion criteria

1. Pregnancy or lactation.
2. Known allergic reactions to components of the pitavastatin calcium tablets.
3. Patients with ALAT and ASAT levels 3 X ULN.
4. Unwillingness to temporarily stop an already prescribed statin, during treatment with pitavastatin.
5. Active infection or fever >38.5°C requiring systemic antibiotic, antifungal or antiviral therapy.
6. Concomitant use of cyclosporin, gemfibrozil, systemic fusidic acid, fibrates, niacin or colchicine.
7. Known to have active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, unexplained elevated liver transaminase levels, and active and chronic hepatitis as determined by the investigator.
8. Suspicion of oral malabsorption, influencing the uptake of drugs from the ileum, such as Morbus Crohn.
9. Treatment with another investigational drug or other intervention within 30 days prior to enrolment or within 5 half-lives of the investigational product, whichever is longer.

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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12 participants in 3 patient groups

Dose group 1: 16 mg

Experimental group

Description:

Pitavastatin 16 mg via oral route in the form of daily tablets for 6 days before SOC surgery

Treatment:

Drug: Pitavastatin calcium

Dose group 2: 32 mg

Experimental group

Description:

Pitavastatin 32 mg via oral route in the form of daily tablets for 6 days before SOC surgery

Treatment:

Drug: Pitavastatin calcium

Dose group 3: 48 mg

Experimental group

Description:

Pitavastatin 48 mg via oral route in the form of daily tablets for 6 days before SOC surgery

Treatment:

Drug: Pitavastatin calcium