Potentiation of Chemotherapy in Brain Tumors by Zinc

• ClinicalTrials.gov Identifier: NCT04488783
• Recruitment Status: Recruiting
• First Posted: July 28, 2020
• Last Update Posted: July 28, 2020
• Sponsor: Sheba Medical Center
• Information provided by (Responsible Party): Dr. Leor Zach, MD, Sheba Medical Center

Study Description

Brief Summary:

Glioblastoma (GB) is the most common and aggressive type of primary malignant brain tumor in adults. Despite advances in surgical resection, radiotherapy and chemotherapy, prognosis remains very poor. Temozolomide (TMZ) as an alkylating agent has become part of GBM management but it has contributed only marginally to prolongation of life in GBM patients. Our aim is to evaluate the therapeutic potential of the trace element zinc to facilitate temozolomide tumor cell toxicity in GBM. P53 gene is inactive/mutant in most of these patients which may affect the resistance to apoptosis of tumor cells by chemotherapy. Zinc (Zn) has a crucial role in the biology of p53, in that p53 binds to DNA through a structurally complex domain stabilized by zinc atom. We have shown that the cytotoxic activity of TMZ is substantially increased with the addition of zinc in vitro with GBM cell lines as well as in vivo, with intracranial GBM xenografts. Numerous studies of zinc in animal models and in human subjects support its use in the treatment and possibly the prevention of cancer. Zinc has been consumed by the public as an essential mineral (and thus is category A drug) in concentrations which allows this effect with Temozolomide. Vitamin C could add to this by priming the immune system for lymphocyte- linked cancer killing. The vitamin c increases the number of tumor infiltrating lymphocytes and enhances the activation of the immune system.We propose a single arm phase II clinical trial in 30 newly diagnosed GBM patients who will be treated with the standard chemo-radiotherapy with the addition of zinc and vitamin C.

Condition or disease	Intervention/treatment	Phase
Newly Diagnosed Glioblastoma Who Underwent at Least Partial Resection of the Tumor Surgically	Dietary Supplement: zinc and ascorbate	Not Applicable

Detailed Description:

We propose a single arm phase II clinical trial in 30 newly diagnosed GBM patients who will be treated with the standard chemo-radiotherapy with the addition of daily zinc. We will follow the toxicity, Progression free survival and overall survival of this group of patients. We hope to demonstrate the anti-tumor activity of zinc that will enhance the activity of temozolomide chemotherapy in adult glioblastoma patients. We will also follow the safety and monitor quality of life during treatment. In this study, we will compare results of patients receiving zinc to historical patient data. We will review patient portfolios with GB tumors that received treatment as the subjects in this study in the last five years before the study began. Collecting the data and separating the identified data from the file in a way that cannot be retrieved in any way will be done by a staff member from Dr Ruty Shai's laboratory who is authorized to open medical files. We will adjust the age and number of patients in each gender. Data collected: date of birth, age of disease development, gender, data after receiving treatment: Progression free survival and overall survival of this group of patients, side effects, and quality of life.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Potentiation of Chemotherapy in Brain Tumors by Zinc
• Estimated Study Start Date: July 30, 2020
• Estimated Primary Completion Date: July 30, 2022
• Estimated Study Completion Date: December 30, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Glioblastoma patients; newly diagnosed GB who underwent at least partial resection of the tumor surgically	Dietary Supplement: zinc and ascorbate; oral zinc and ascorbate

Outcome Measures

Primary Outcome Measures :

1. progression free survival (PFS) [ Time Frame: year 1 ]
2. overall survival (OS) [ Time Frame: year 2 ]

Secondary Outcome Measures :

1. Tcell count [ Time Frame: year 2 ]
   Blood test
2. Level of Interleukin 6 [ Time Frame: year 2 ]
   Interleukin 6 and Tumor Necrosis Factor quantification
3. Tumor Necrosis Factor quantification [ Time Frame: year 2 ]
   Blood test

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 90 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Males and Females,
• age ≥ 18 years old,
• newly diagnosed GBM, Karnofsky performance status of ≥ 70,
• after partial resection or gross tumor resection (GTR) who recovered from surgical resection.

Exclusion Criteria:

• GB patients with less than 20% of tumor removed,
• Prior treatment for GB (other than surgical resection),
• any known malignancy outside of the brain in the last 5 years,
• in ability to swallow drugs.

Contacts and Locations

Contacts

Contact: Ruty Shai, PhD; 972-543938318; ruty.shai@sheba.health.gov.il

Locations

Israel

Sheba Medical Center; Recruiting

Ramat Gan, Israel

Contact: Ruty Shai, Ph.D 972543938318 ruty.shai@sheba.health.gov.il

Principal Investigator: Ruty Shai, Ph.D

Sponsors and Collaborators

Sheba Medical Center

More Information

• Responsible Party: Dr. Leor Zach, MD, MD, Sheba Medical Center
• ClinicalTrials.gov Identifier: NCT04488783
• Other Study ID Numbers: 4266-17-SMC
• First Posted: July 28, 2020
• Last Update Posted: July 28, 2020
• Last Verified: July 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Dr. Leor Zach, MD, Sheba Medical Center:

GBM; glioblastoma; zinc; vitamin C

Additional relevant MeSH terms:

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