Oral Gallium Maltolate for Recurrent Glioblastoma

Официальное название

A Phase 0 Clinical Trial of Oral Gallium Maltolate for Recurrent Glioblastoma

Обзор

This is a Phase 0 investigational study to assess the central nervous system penetration and tumoral concentration of gallium in patients with recurrent glioblastoma administered with preoperative gallium maltolate.

Подробное описание

Rationale: Currently, recruitment has concluded for a Phase 1 trial assessing in patients with GBM. Preliminary analyses have demonstrated gallium maltolate is both safe and potentially efficacious in treating glioblastoma. However, while gallium maltolate has been well-tolerated, further correlative analyses are necessary to confirm the drug's ability to act within the brain.

Вмешательства

• Препарат Gallium Maltolate
  Gallium Maltolate will be administered at a total daily dose of 2500 mg.
• Процедура Surgical Intervention
  Patients will be scheduled for surgical intervention (needle biopsy or resection) as deemed necessary by the clinical team after 14 ± 5 days of oral Gallium Maltolate administration.

Первичные конечные точки

• Glioma Tissue Difference [Срок оценки: 3 months]

Критерии участия

Критерии включения

• Age >18 years
• 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of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.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 subjects must have a prior histological diagnosis of Glioblastoma (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).
• Subjects are required to have received standard treatment which consists of radiotherapy and temozolomide (i.e., the Stupp Protocol). Treatment with adjuvant temozolomide 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 absolute neutrophil count (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.
• Subjects must be symptomatically stable, without new or rapidly worsening neurologic deficits for a minimum of 14 days prior to screening.
• Subjects must have been reviewed by a multidisciplinary group comprised of Central Nervous System oncology experts (which could include neuro-oncology, radiation oncology, neurosurgery, and radiology) to have radiographic signs of tumor progression (as defined by the RANO criteria) requiring surgical pathologic specimen (stereotactic biopsy or craniotomy for debulking/resection).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Subjects must have adequate bone marrow function as evidenced by:

• an 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
• Subjects must have adequate hepatic and renal function based on the following laboratory tests:

• Alanine aminotransferase (ALT) ≤ 2 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) ≤ 2 x ULN
• Alkaline phosphatase ≤ 2 x ULN
• Total bilirubin ≤ 2 x ULN
• 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 21 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 \[e.g., calendar, ovulation, symptothermal, postovulation methods\] 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.)
• Subjects 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.

Критерии исключения

• 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 (forced expiratory volume (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.
• Subjects who have not completed all standard-of-care treatments including surgical procedures and radiation therapy.
• Subjects with new or worsening neurologic deficits that would require surgical treatment before complete administration of the study drug.
• Inability to tolerate an oral medication or keep pills down.
• Subjects who are pregnant or nursing.
• Subjects with any condition which, in the investigator's opinion, makes the patient unsuitable for study participation.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Froedtert & the Medical College of Wisconsin — Milwaukee

Идентификаторы

NCT: NCT07515924 · IIT-DESAI-GBM-GALLIUMMALTOLATE

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗