Oral Gallium Maltolate for the Treatment of Relapsed and Refractory Glioblastoma

NCT04319276 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: PRO00041263
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 1 investigational study to assess the safety and preliminary efficacy of oral gallium maltolate (GaM) in participants with relapsed glioblastoma (GBM).

Conditions

Glioblastoma

Keywords

gallium maltolate; Glioblastoma

Outcome Measures

Primary Outcomes (1)

• Maximum-tolerated dose.

  This will be determined from the incidence of dose limiting toxicities at each dosage.

  Each 28-day cohort

Secondary Outcomes (3)

• Progression-free survival

  6 months

• Overall survival

  6 months

• Dose-limiting toxicity

  28 days for each cohort

Study Arms (6)

Dose-escalation Phase (500 mg)

EXPERIMENTAL

This is a 3 + 3 design. Participants will be entered sequentially. If 0 of 3 participants has a dose-limiting toxicity (DLT), new participants may be entered at the next higher dose level. If 1 of 3 participants has a DLT, up to 3 more participants are to be treated at that same dose level. If 0 of the additional 3 participants at that dose level has a DLT, new participants may be entered at the next higher dose level. If 1 or more of the additional 3 participants experience a DLT, 0 participants are to be started at that dose level and the preceding dose is the maximum-tolerated dose (MTD). If 2 of 3 of the dosed participants has a DLT on the first dose level, the drug will be administered at a lower dose. If 0 of 3 participants has a DLT at the highest dose level, an additional 3 participants will be enrolled to ensure that 6 participants are treated at the MTD. The MTD is the highest dose level at which no more than 1 of 6 treated participants, experiences a DLT.

Drug: Gallium maltolate (500 mg)

Dose-escalation Phase (1,000 mg)

EXPERIMENTAL

This is a 3 + 3 design. Participants will be entered sequentially. If 0 of 3 participants has a dose-limiting toxicity (DLT), new participants may be entered at the next higher dose level. If 1 of 3 participants has a DLT, up to 3 more participants are to be treated at that same dose level. If 0 of the additional 3 participants at that dose level has a DLT, new participants may be entered at the next higher dose level. If 1 or more of the additional 3 participants experience a DLT, 0 participants are to be started at that dose level and the preceding dose is the maximum-tolerated dose (MTD). If 2 of 3 of the dosed participants has a DLT on the first dose level, the drug will be administered at a lower dose. If 0 of 3 participants has a DLT at the highest dose level, an additional 3 participants will be enrolled to ensure that 6 participants are treated at the MTD. The MTD is the highest dose level at which no more than 1 of 6 treated participants, experiences a DLT.

Drug: Gallium maltolate (1,000 mg)

Dose-escalation Phase (1,500 mg)

EXPERIMENTAL

This is a 3 + 3 design. Participants will be entered sequentially. If 0 of 3 participants has a dose-limiting toxicity (DLT), new participants may be entered at the next higher dose level. If 1 of 3 participants has a DLT, up to 3 more participants are to be treated at that same dose level. If 0 of the additional 3 participants at that dose level has a DLT, new participants may be entered at the next higher dose level. If 1 or more of the additional 3 participants experience a DLT, 0 participants are to be started at that dose level and the preceding dose is the maximum-tolerated dose (MTD). If 2 of 3 of the dosed participants has a DLT on the first dose level, the drug will be administered at a lower dose. If 0 of 3 participants has a DLT at the highest dose level, an additional 3 participants will be enrolled to ensure that 6 participants are treated at the MTD. The MTD is the highest dose level at which no more than 1 of 6 treated participants, experiences a DLT.

Drug: Gallium maltolate (1,500 mg)

Dose-escalation Phase (2,000 mg)

EXPERIMENTAL

This is a 3 + 3 design. Participants will be entered sequentially. If 0 of 3 participants has a dose-limiting toxicity (DLT), new participants may be entered at the next higher dose level. If 1 of 3 participants has a DLT, up to 3 more participants are to be treated at that same dose level. If 0 of the additional 3 participants at that dose level has a DLT, new participants may be entered at the next higher dose level. If 1 or more of the additional 3 participants experience a DLT, 0 participants are to be started at that dose level and the preceding dose is the maximum-tolerated dose (MTD). If 2 of 3 of the dosed participants has a DLT on the first dose level, the drug will be administered at a lower dose. If 0 of 3 participants has a DLT at the highest dose level, an additional 3 participants will be enrolled to ensure that 6 participants are treated at the MTD. The MTD is the highest dose level at which no more than 1 of 6 treated participants, experiences a DLT.

Drug: Gallium maltolate (2,000 mg)

Dose-escalation Phase (2,500 mg)

EXPERIMENTAL

This is a 3 + 3 design. Participants will be entered sequentially. If 0 of 3 participants has a dose-limiting toxicity (DLT), new participants may be entered at the next higher dose level. If 1 of 3 participants has a DLT, up to 3 more participants are to be treated at that same dose level. If 0 of the additional 3 participants at that dose level has a DLT, new participants may be entered at the next higher dose level. If 1 or more of the additional 3 participants experience a DLT, 0 participants are to be started at that dose level and the preceding dose is the maximum-tolerated dose (MTD). If 2 of 3 of the dosed participants has a DLT on the first dose level, the drug will be administered at a lower dose. If 0 of 3 participants has a DLT at the highest dose level, an additional 3 participants will be enrolled to ensure that 6 participants are treated at the MTD. The MTD is the highest dose level at which no more than 1 of 6 treated participants, experiences a DLT.

Drug: Gallium maltolate (2,500 mg)

Dose-expansion Phase

EXPERIMENTAL

A minimum of six participants will be enrolled in the dose expansion phase for a total of 12 subjects at the recommended phase 2 dose.

Drug: Gallium maltolate (recommended phase 2 dose)

Interventions

Gallium maltolate (500 mg) DRUG

This is a 3+3 design. The doses are as follows: level -1: 500 mg every other day; level 0: (starting dose) 500 mg daily; level 1: 1,000 mg daily; level 2: 1,500 mg daily; level 3: 2,000 mg daily; level 4: 2,500 mg daily.

Also known as: Chemical Abstracts Service (CAS) 108560-70-9

Dose-escalation Phase (500 mg)

Gallium maltolate (1,000 mg) DRUG

This is a 3+3 design. The doses are as follows: level -1: 500 mg every other day; level 0: (starting dose) 500 mg daily; level 1: 1,000 mg daily; level 2: 1,500 mg daily; level 3: 2,000 mg daily; level 4: 2,500 mg daily.

Also known as: CAS 108560-70-9

Dose-escalation Phase (1,000 mg)

Gallium maltolate (1,500 mg) DRUG

This is a 3+3 design. The doses are as follows: level -1: 500 mg every other day; level 0: (starting dose) 500 mg daily; level 1: 1,000 mg daily; level 2: 1,500 mg daily; level 3: 2,000 mg daily; level 4: 2,500 mg daily.

Also known as: CAS 108560-70-9

Dose-escalation Phase (1,500 mg)

Gallium maltolate (2,000 mg) DRUG

This is a 3+3 design. The doses are as follows: level -1: 500 mg every other day; level 0: (starting dose) 500 mg daily; level 1: 1,000 mg daily; level 2: 1,500 mg daily; level 3: 2,000 mg daily; level 4: 2,500 mg daily.

Also known as: CAS 108560-70-9

Dose-escalation Phase (2,000 mg)

Gallium maltolate (2,500 mg) DRUG

This is a 3+3 design. The doses are as follows: level -1: 500 mg every other day; level 0: (starting dose) 500 mg daily; level 1: 1,000 mg daily; level 2: 1,500 mg daily; level 3: 2,000 mg daily; level 4: 2,500 mg daily.

Also known as: CAS 108560-70-9

Dose-escalation Phase (2,500 mg)

Gallium maltolate (recommended phase 2 dose) DRUG

The maximum-tolerated dose (recommended phase 2 dose).

Also known as: CAS 108560-70-9

Dose-expansion Phase

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntary written consent must be obtained before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
• All patients must have a prior histological diagnosis of GBM (WHO grade IV) or molecular features of GBM (per the 6th volume of Central Nervous System Tumors in the 5th edition of the WHO Classification of Tumors).
• Patients are required to have received standard treatment which consists of radiotherapy and temozolomide \[i.e., the Stupp Protocol (3)\] Treatment with adjuvant temozolimide must be completed at least four weeks prior to GaM administration to avoid potential for overlapping toxicity with GaM. Although the half-life (T½) of temozolomide is 1.8 hours and it would be expected to be cleared by five half-lives, some patients receiving temozolomide may experience a delayed suppression of their ANC. Hence, a four-week interval between completion of temozolomide and GaM will be required. There is no maximum limit to the amount of chemotherapy or radiation patients have received prior to enrollment.
• Patients must have measurable disease that can be assessed for response to treatment as defined by the Response Assessment in Neuro-Oncology (RANO) criteria which incorporates MRI assessment and clinical factors. In the absence of measurable disease, pathologic confirmation of recurrent disease is required.
• Male or female subjects must be ≥18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Patients must have adequate bone marrow function as evidenced by:
• an absolute neutrophil count (ANC) of \>1500/μL (stable off any growth factor within one week of study drug administration
• Hemoglobin \> 9 g/dL
• Platelet count \> 100.000/μL without transfusion within one week
• Patients must have adequate hepatic and renal function based on the following laboratory tests: a. alanine transaminase (ALT) ≤ 2 x upper limits of normal (ULN) b. aspartate aminotransferase (AST) ≤ 2 x ULN c. Alkaline phosphatase ≤ 2 x ULN d. Total bilirubin ≤ 2 x ULN e. Creatinine \< 1.5 mg/dL or glomerular filtration rate (GFR) by Modification of Diet in Renal Disease (MDRD) \> 45
• Female subjects must meet one of the following:
• Postmenopausal for at least one year before enrollment, OR
• Surgically sterile (i.e., undergone a hysterectomy or bilateral oophorectomy), OR
• If subject is of childbearing potential (defined as not satisfying either of the above two criteria), agree to practice two acceptable methods of contraception (combination methods require use of two of the following: diaphragm with spermicide, cervical cap with spermicide, contraceptive sponge, male or female condom, hormonal contraceptive) from the time of signing of the informed consent form through 21days after the last dose of study agent, OR

You may not qualify if:

• Presence of other active malignant disease diagnosed within 12 months, with the exception of adequately treated non-melanoma skin cancer, adequately treated melanoma grade 2 or less, or cervical intraepithelial neoplasia. Active malignancy is malignancy receiving treatment.
• Prior chemotherapy or radiotherapy within 14 days of study entry.
• Known hypersensitivity to or intolerance to gallium-based medications.
• Concurrent use of cytotoxic chemotherapy is not permitted.
• Unstable or severe concurrent medical conditions such as severe heart (New York Heart Association Class 3 or 4) or known lung (FEV \<50%) disease, uncontrolled diabetes mellitus.
• History of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis, or symptomatic pleural effusion.
• Patients who have not completed all standard-of-care treatments including surgical procedures and radiation therapy.
• Inability to tolerate an oral medication or keep pills down.
• Patients who are pregnant or nursing.
• Patients with any condition which, in the investigator's opinion, makes the patient unsuitable for study participation.

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Study Sites (1)

Froedtert Hospital & the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

gallium maltolate

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Jennifer Connelly, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 20, 2020
• First Posted: March 24, 2020
• Study Start: November 11, 2022
• Primary Completion: February 13, 2025
• Study Completion (Estimated): March 1, 2027
• Last Updated: November 3, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)