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

Primary Purpose

Glioblastoma Multiforme, Adult, Recurrent Glioblastoma

Status
Not yet recruiting
Phase
Early Phase 1
Locations
Netherlands
Study Type
Interventional
Intervention
Pitavastatin calcium
Sponsored by
C.Dirven
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Glioblastoma Multiforme, Adult focused on measuring Phase 0, GBM, Glioma, Pitavastatin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Eligible for resection of a suspected primary glioblastoma or a recurrent glioblastoma. MRI- measurable disease preoperatively, defined as at least 1 contrast-enhancing lesion, with 1 perpendicular measurement of at least 0.5 cm. Adequate Renal Function defined as: estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 by Chronic Disease Epidemiology Collaboration (CKD-EPI) equation. CK elevation 3 X ULN. Ability to understand and the willingness to sign a written informed consent document. 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. Willingness and ability to comply with all scheduled visits, treatment plans, laboratory tests and other procedures. Age ≥18 years at time of consent. Ability and willingness to swallow oral medication. 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. 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. Females of child-bearing potential must agree not to breastfeed starting at screening, and throughout the study period. Exclusion Criteria: Pregnancy or lactation. Known allergic reactions to components of the pitavastatin calcium tablets. Patients with ALAT and ASAT levels 3 X ULN. Unwillingness to temporarily stop an already prescribed statin, during treatment with pitavastatin. Active infection or fever >38.5°C requiring systemic antibiotic, antifungal or antiviral therapy. Concomitant use of cyclosporin, gemfibrozil, systemic fusidic acid, fibrates, niacin or colchicine. 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. Suspicion of oral malabsorption, influencing the uptake of drugs from the ileum, such as Morbus Crohn. 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.

Sites / Locations

  • Erasmus MC

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Dose group 1: 16 mg

Dose group 2: 32 mg

Dose group 3: 48 mg

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

Intratumoral pitavastatin concentration as assessed by LC-MS analysis on tumour tissue.
Detection of pitavastatin in gadolinium enhanced and gadolinium non-enhanced tumour. tissue in relation to serum levels after preoperative administration.

Secondary Outcome Measures

Tolerability of short-term pitavastatin treatment as assesseb by a customized questionnaire related to adverse events found during the use of pitavastatin.
Number of AEs, SAEs and SUSARs collected at the end of the trial. Events will be scored according to CTC criteria version 5.0 (Published November 27th, 2017).
Relation of plasma pitavastatin concentration and intratumoral pitavastatin concentration as assessed by LC-MS analysis on plasma and tumour tissue.
Correlation of pitavastatin concentration in plasma to pitavastatin concentration in different tumour sites(gadolinium enhanced, gadolinium non-enhanced and tumour periphery).

Full Information

First Posted
July 25, 2023
Last Updated
August 3, 2023
Sponsor
C.Dirven
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1. Study Identification

Unique Protocol Identification Number
NCT05977738
Brief Title
Repurposed Drugs in Research for Cancer Clinical Trials- Pitavastatin
Acronym
ReDiReCCT-Pita
Official Title
Phase 0 lead-in Trial of Pitavastatin in Primary and Recurrent Glioblastoma Patients
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
November 2023 (Anticipated)
Primary Completion Date
May 2024 (Anticipated)
Study Completion Date
July 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
C.Dirven

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma Multiforme, Adult, Recurrent Glioblastoma
Keywords
Phase 0, GBM, Glioma, Pitavastatin

7. Study Design

Primary Purpose
Other
Study Phase
Early Phase 1
Interventional Study Model
Sequential Assignment
Model Description
open label, dose-finding, 3+3-like dose-escalation study design
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
18 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Dose group 1: 16 mg
Arm Type
Experimental
Arm Description
Pitavastatin 16 mg via oral route in the form of daily tablets for 6 days before SOC surgery
Arm Title
Dose group 2: 32 mg
Arm Type
Experimental
Arm Description
Pitavastatin 32 mg via oral route in the form of daily tablets for 6 days before SOC surgery
Arm Title
Dose group 3: 48 mg
Arm Type
Experimental
Arm Description
Pitavastatin 48 mg via oral route in the form of daily tablets for 6 days before SOC surgery
Intervention Type
Drug
Intervention Name(s)
Pitavastatin calcium
Other Intervention Name(s)
Alipza
Intervention Description
Daily Pitavastatin administration
Primary Outcome Measure Information:
Title
Intratumoral pitavastatin concentration as assessed by LC-MS analysis on tumour tissue.
Description
Detection of pitavastatin in gadolinium enhanced and gadolinium non-enhanced tumour. tissue in relation to serum levels after preoperative administration.
Time Frame
From the last patient visit of each dose cohort at day 9 to 2 weeks after the last patient visit of each dose cohort.
Secondary Outcome Measure Information:
Title
Tolerability of short-term pitavastatin treatment as assesseb by a customized questionnaire related to adverse events found during the use of pitavastatin.
Description
Number of AEs, SAEs and SUSARs collected at the end of the trial. Events will be scored according to CTC criteria version 5.0 (Published November 27th, 2017).
Time Frame
From the last patient visit of the last dose cohort to 2 weeks after the last patient visit of the last dose cohort on day 9.
Title
Relation of plasma pitavastatin concentration and intratumoral pitavastatin concentration as assessed by LC-MS analysis on plasma and tumour tissue.
Description
Correlation of pitavastatin concentration in plasma to pitavastatin concentration in different tumour sites(gadolinium enhanced, gadolinium non-enhanced and tumour periphery).
Time Frame
From the moment the LC-MS analysis of the last patient tumour tissue and plasma is performed to two weeks after the last patient visit on day 9 of the last dose cohort.
Other Pre-specified Outcome Measures:
Title
Differences in RNA expression after pitavastatin exposure in tumour tissue using RNA sequencing.
Description
Using RNA sequencing on collected tumour samples from the gadolinium enhanced part of the tumour.
Time Frame
From the last tumour tissue acquisition of the last patient of the last dose cohort to 3 months after all tissue is collected.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Eligible for resection of a suspected primary glioblastoma or a recurrent glioblastoma. MRI- measurable disease preoperatively, defined as at least 1 contrast-enhancing lesion, with 1 perpendicular measurement of at least 0.5 cm. Adequate Renal Function defined as: estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 by Chronic Disease Epidemiology Collaboration (CKD-EPI) equation. CK elevation 3 X ULN. Ability to understand and the willingness to sign a written informed consent document. 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. Willingness and ability to comply with all scheduled visits, treatment plans, laboratory tests and other procedures. Age ≥18 years at time of consent. Ability and willingness to swallow oral medication. 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. 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. Females of child-bearing potential must agree not to breastfeed starting at screening, and throughout the study period. Exclusion Criteria: Pregnancy or lactation. Known allergic reactions to components of the pitavastatin calcium tablets. Patients with ALAT and ASAT levels 3 X ULN. Unwillingness to temporarily stop an already prescribed statin, during treatment with pitavastatin. Active infection or fever >38.5°C requiring systemic antibiotic, antifungal or antiviral therapy. Concomitant use of cyclosporin, gemfibrozil, systemic fusidic acid, fibrates, niacin or colchicine. 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. Suspicion of oral malabsorption, influencing the uptake of drugs from the ileum, such as Morbus Crohn. 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Puspha Achaiber Sing, MD, MSc
Phone
+31107035993
Email
p.achaibersing@erasmusmc.nl
First Name & Middle Initial & Last Name or Official Title & Degree
Judith Verhagen, PhD
Phone
+31650032401
Email
j.verhagen-oldenampsen@erasmusmc.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clemens Dirven, MD, PhD
Organizational Affiliation
Erasmus Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Erasmus MC
City
Rotterdam
ZIP/Postal Code
3015 GE
Country
Netherlands
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Puspha Achaiber Sing, MSc
Phone
+31107035993
Email
p.achaibersing@erasmusmc.nl
First Name & Middle Initial & Last Name & Degree
Judith Verhagen, PhD
Phone
+31650032401
Email
j.verhagen-oldenampsen@erasmusmc.nl
First Name & Middle Initial & Last Name & Degree
Clemens Dirven, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD
Undecided

Learn more about this trial

Repurposed Drugs in Research for Cancer Clinical Trials- Pitavastatin

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