Using oral gallium maltolate to treat relapsed glioblastoma

A Phase 1 Clinical Trial of Oral Gallium Maltolate for the Treatment of Relapsed and Refractory Glioblastoma

This study is testing if a new oral treatment called gallium maltolate can help people with relapsed glioblastoma feel better and how safe it is to use.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 36 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Medical College of Wisconsin (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 1 site (Milwaukee, Wisconsin)
• Trial ID: NCT04319276 on ClinicalTrials.gov

What this trial studies

This phase 1 study investigates the safety and preliminary efficacy of oral gallium maltolate (GaM) in patients with relapsed and treatment-refractory glioblastoma (GBM). It is a single-center, open-label trial that employs a dose escalation design to assess the antineoplastic activity and tolerance of GaM. Participants will receive varying doses of GaM, with a maximum of 36 individuals enrolled in the dose escalation phase. The study aims to determine the appropriate dosage with limited side effects based on previous trials.

Who should consider this trial

Good fit: Ideal candidates are individuals with a confirmed diagnosis of relapsed glioblastoma who have previously undergone standard treatment.

Not a fit: Patients who have not been diagnosed with glioblastoma or those who have not received prior standard treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with relapsed glioblastoma who have limited treatment alternatives.

How similar studies have performed: While gallium maltolate has been studied in other solid tumors, this specific application in relapsed glioblastoma is novel and has not been previously tested.

Eligibility criteria

Inclusion Criteria

1. 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of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
2. 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).
3. 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.
4. 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.
5. Male or female subjects must be ≥18 years of age.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
7. Patients must have adequate bone marrow function as evidenced by:

   1. an absolute neutrophil count (ANC) of \>1500/μL (stable off any growth factor within one week of study drug administration
   2. Hemoglobin \> 9 g/dL
   3. Platelet count \> 100.000/μL without transfusion within one week
8. 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
9. 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
   * Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, postovulation methods\] and withdrawal are not acceptable contraception methods.)
10. Male subjects, even if surgically sterilized (i.e., status post-vasectomy), must agree to one of the following:

    * Practice effective barrier contraception during the entire study period and through 60 calendar days after the last dose of study agent, OR
    * Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception.)
11. Patients taking oral iron supplements or iron chelators must discontinue these medications at least one week prior to starting GaM since these agents may impact on the efficacy of GaM. Drug-drug interactions between GaM and other concomitant medications have not been reported.

Exclusion Criteria

1. 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.
2. Prior chemotherapy or radiotherapy within 14 days of study entry.
3. Known hypersensitivity to or intolerance to gallium-based medications.
4. Concurrent use of cytotoxic chemotherapy is not permitted.
5. 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.
6. 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.
7. Patients who have not completed all standard-of-care treatments including surgical procedures and radiation therapy.
8. Inability to tolerate an oral medication or keep pills down.
9. Patients who are pregnant or nursing.
10. Patients with any condition which, in the investigator's opinion, makes the patient unsuitable for study participation.

Where this trial is running

Milwaukee, Wisconsin

• Froedtert Hospital & the Medical College of Wisconsin — Milwaukee, Wisconsin, United States (Recruiting)

Study contacts

• Principal investigator: Jennifer Connelly, MD — Medical College of Wisconsin
• Study coordinator: Medical College of Wisconsin Cancer Center Clinical Trials Office

Conditions Glioblastoma; gallium maltolate