A prospective randomized open-label phase II clinical study evaluating the efficacy and safety of zoledronic acid addition to standard therapy in patients with glioblastoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pauls Stradins Clinical University Hospital

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10], Diseases [C] - Neoplasms [C04]

Trial duration

6 Mar 2025 → ongoing

Decision date (initial)

2025-02-28

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Pauls Stradins Clinical University hospital

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

To evaluate whether adding zoledronic acid to standard chemotherapy improves overall survival (OS) and progression-free survival (PFS) in patients with glioblastoma.

Secondary objectives 2

1. To assess the impact of zoledronic acid addition on objective response rate (ORR) and duration of response (DOR) in patients with glioblastoma.
2. To evaluate the safety and tolerability of zoledronic acid when used in conjunction with standard therapy

Conditions and MedDRA coding

Glioblastoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Participants who are capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the Informed Consent Form and in this protocol
2. Participants (females and males) who are age ≥ 18 years at the time of signing Informed Consent Form
3. IDH negative (wild type) glioblastoma
4. Participants who have multicentric (the presence of two or more tumor foci within different lobes of brain) and/or multifocal (the presence of two or more tumor foci within a single lobes of brain) glioblastoma are eligible
5. Participants must have undergone surgery or stereotactic biopsy of the glioblastoma
6. Participants must have completed concurrent radio-chemotherapy prior to randomization. A washout period of at least 28 days is required between the last chemotherapy dose and randomization
7. Participants for whom resolution of all acute toxic effects of prior anti-cancer therapy to NCI CTCAE v5.0 Grade 1 or better (except alopecia, Grade 2 or better peripheral neuropathy, arthralgia or other toxicities not considered a safety risk for the participant per the investigator’s judgment)
8. Participants who have Eastern Cooperative Oncology Group Performance (ECOG) Performance Status 0, 1 or 2. Also ECOG 3 if it is caused by irreversible neurological deficit due to glioblastoma
9. Participants who are able and willing to swallow and retain oral medication
10. Participants who have adequate organ function as defined by the following criteria: ANC higher than 1x 109/L, Platelet count higher than 100 x 109/L, AST and serum ALT lower than 3 times ULN, ALP lower than 3 times ULN, Hemoglobin higher than 80 g/L, Estimated creatinine clearance more than 60 mL/min and calculated per institutional guidelines, Serum bilirubin lower than 1.5 times ULN with the following exception: Participants with known Gilbert syndrome: lower than 3 times ULN
11. For women of childbearing potential: participants who agree to remain abstinent (refrain from heterosexual intercourse) or use contraception as defined below: o Women must remain abstinent or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for 90 days after the final dose of zoledronic acid or temozolamide. A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and is not permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, and/or uterus) or another cause as determined by the investigator (e.g., Müllerian agenesis). Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, and copper intrauterine devices. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the individual. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception. If required per local guidelines or regulations, information about the reliability of abstinence will be described in the local Informed Consent Form
12. For men assigned: participants who agree to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agree to refrain from donating sperm, as defined below: o With a female partner of childbearing potential or pregnant female partner, men must remain abstinent or use a condom during the treatment period and for 90 days after the final dose of zoledronic acid or temozolamide to avoid exposing the embryo. Men must refrain from donating sperm during this same period. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the individual. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of preventing drug exposure. If required per local guidelines or regulations, information about the reliability of abstinence will be described in the local Informed Consent Form.

Exclusion criteria 12

1. Participants who are pregnant or breastfeeding, or intending to become pregnant during the study or within 90 days after the final dose of zoledronic acid or temozolamide, or within the time period specified per local prescribing guidelines after the final dose of chemotherapy
2. Participants who have received treatment with bisphosphonates within 2 years prior to initiation of study treatment or is currently enrolled in any other type of medical research judged by the investigator not to be scientifically or medically compatible with this study
3. Participants who have any other active malignancy
4. Participants who have relapsed glioblastoma or previous other type of glioma who has transformed to glioblastoma
5. Participants who have a known clinically significant history of liver disease consistent with Child-Pugh Class C, including hepatitis (e.g., hepatitis B virus [HBV] or hepatitis C virus [HCV]), current alcohol abuse, cirrhosis, or positive test for viral hepatitis, as defined: Active infection is defined as requiring treatment with antiviral therapy or presence of positive test results for hepatitis B (hepatitis B surface antigen and/or total hepatitis B core antibody [HBcAb]) or HCV antibody; Participants who test positive for HBcAb are eligible only if test results are also positive for hepatitis B surface antibody and polymerase chain reaction is negative for HBV DNA; Participants who are positive for HCV serology are eligible only if testing for HCV RNA is negative
6. Participants who have acute or chronic kidney failure and GFR less than 60 ml/min
7. Participants who have serious mouth and dental infections and may need a dental procedures (except dental filling) in near future
8. Participants who have level of calcium in blood less than 2 mmol/l
9. Participants who have a known allergy or hypersensitivity to any of the study drugs or any of their excipients
10. Participants who have had a serious infection requiring oral or IV antibiotics within 14 days prior to screening or other clinically significant infection within 14 days prior to screening
11. Participants who have had any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes an individual's safe participation in and completion of the study
12. Participants who are unable or unwilling to comply with the requirements of the protocol in the opinion of the investigator

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Overall Survival (OS): Time from randomization to death from any cause.
2. Progression-Free Survival (PFS): Time from randomization to disease progression (per RANO criteria) or death, whichever occurs first.

Secondary endpoints 3

1. Objective Response Rate (ORR): Proportion of patients achieving a complete or partial response per RANO criteria.
2. Duration of Response (DOR): Time from the initial response to disease progression or death in patients who respond to treatment.
3. Safety and Tolerability: Incidence of adverse events (AEs), serious adverse events (SAEs), and treatment-related discontinuations, assessed according to NCI CTCAE v5.0 criteria.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pauls Stradins Clinical University Hospital

Sponsor organisation

Pauls Stradins Clinical University Hospital

Address

Pilsonu Iela 13

City

Riga

Postcode

1002

Country

Latvia

Scientific contact point

Organisation

Pauls Stradins Clinical University Hospital

Contact name

Sigita Hasnere

Public contact point

Organisation

Pauls Stradins Clinical University Hospital

Contact name

Sigita Hasnere

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications