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Oral Gallium Maltolate for the Treatment of Relapsed and Refractory Glioblastoma

Primary Purpose

Glioblastoma

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Gallium maltolate (500 mg)
Gallium maltolate (1,000 mg)
Gallium maltolate (1,500 mg)
Gallium maltolate (recommended phase 2 dose)
Sponsored by
Medical College of Wisconsin
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioblastoma focused on measuring gallium maltolate, Glioblastoma

Eligibility Criteria

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

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of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.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.

Sites / Locations

  • Froedtert Hospital & the Medical College of WisconsinRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Dose-escalation Phase (500 mg)

Dose-escalation Phase (1,000 mg)

Dose-escalation Phase (1,500 mg)

Dose-expansion Phase

Arm Description

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Progression-free survival
This measure is the number of months participants remain free from evidence of disease. Imaging will be done every eight weeks and reported at six months.
Overall survival
Overall survival is determined as the average number of months subjects survived following enrollment.
Dose-limiting toxicity
Number of participants experiencing a dose limiting toxicity.

Full Information

First Posted
March 20, 2020
Last Updated
September 27, 2023
Sponsor
Medical College of Wisconsin
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1. Study Identification

Unique Protocol Identification Number
NCT04319276
Brief Title
Oral Gallium Maltolate for the Treatment of Relapsed and Refractory Glioblastoma
Official Title
A Phase 1 Clinical Trial of Oral Gallium Maltolate for the Treatment of Relapsed and Refractory Glioblastoma
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 11, 2022 (Actual)
Primary Completion Date
December 2025 (Anticipated)
Study Completion Date
December 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Medical College of Wisconsin

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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).
Detailed Description
This is a prospective, single-center, single-arm, open-label phase 1 study to determine the antineoplastic activity, safety and tolerance of GaM in participants with relapsed, treatment-refractory GBM. Although GaM has been studied in previous phase 1 clinical trials in normal individuals and in participants with a variety of different solid tumors, it has never been evaluated in this population of participants. Dosages in this study have been defined to have limited side effects in other phase 1 trials. The maximum number of participants to enroll in the dose escalation part will not exceed 24. The trial will follow a 3 + 3 phase I dose escalation design.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma
Keywords
gallium maltolate, Glioblastoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Dose-escalation Phase (500 mg)
Arm Type
Experimental
Arm Description
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.
Arm Title
Dose-escalation Phase (1,000 mg)
Arm Type
Experimental
Arm Description
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.
Arm Title
Dose-escalation Phase (1,500 mg)
Arm Type
Experimental
Arm Description
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.
Arm Title
Dose-expansion Phase
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Gallium maltolate (500 mg)
Other Intervention Name(s)
Chemical Abstracts Service (CAS) 108560-70-9
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Gallium maltolate (1,000 mg)
Other Intervention Name(s)
CAS 108560-70-9
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Gallium maltolate (1,500 mg)
Other Intervention Name(s)
CAS 108560-70-9
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Gallium maltolate (recommended phase 2 dose)
Other Intervention Name(s)
CAS 108560-70-9
Intervention Description
The maximum-tolerated dose (recommended phase 2 dose).
Primary Outcome Measure Information:
Title
Maximum-tolerated dose.
Description
This will be determined from the incidence of dose limiting toxicities at each dosage.
Time Frame
Each 28-day cohort
Secondary Outcome Measure Information:
Title
Progression-free survival
Description
This measure is the number of months participants remain free from evidence of disease. Imaging will be done every eight weeks and reported at six months.
Time Frame
6 months
Title
Overall survival
Description
Overall survival is determined as the average number of months subjects survived following enrollment.
Time Frame
6 months
Title
Dose-limiting toxicity
Description
Number of participants experiencing a dose limiting toxicity.
Time Frame
28 days for each cohort

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria 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 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.) 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.) 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 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Medical College of Wisconsin Cancer Center Clinical Trials Office
Phone
414-805-8900
Email
cccto@mcw.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jennifer Connelly, MD
Organizational Affiliation
Medical College of Wisconsin
Official's Role
Principal Investigator
Facility Information:
Facility Name
Froedtert Hospital & the Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cancer Center Clinical Trials Office
Phone
866-680-0505
Ext
8900
Email
cccto@mcw.edu

12. IPD Sharing Statement

Plan to Share IPD
No

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Oral Gallium Maltolate for the Treatment of Relapsed and Refractory Glioblastoma

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