Neoplasms

All Conditions

Rare Diseases

Glioblastoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Micronutrients

All Drugs and Chemicals

Antineoplastic Agents

Hematinics

Pharmaceutical Solutions

Vitamins

Ascorbic Acid

Temozolomide

Iron

Alkylating Agents

Ferrosoferric Oxide

Trace Elements

Antineoplastic Agents, Alkylating

Antioxidants

Protective Agents

Parenteral Nutrition Solutions

Vitamin C

Radiation Phase

* Ascorbate: 87.5 g administered intravenously (IV) three times each calendar week for approximately 8 weeks.
* Ferumoxytol: 512 g administered intravenously (IV) the day before radiation and then during weeks 5 to 6 of radiation therapy.
* Radiation: 61.2 Gray (given 1.8 Gray once daily, 5 days per week, for about 7 weeks) or 60 Gray (2.0 Gray once daily for 5 days per week for about 6 weeks)
* Temozolomide: 75 mg/m2, taken orally, once daily, every day, for up to 49 days or until radiation is completed (whichever comes first).

Adjuvant Phase

* Temozolomide: 150 to 200 mg/m2, taken orally, once daily, for five days out of 28 days (where 28 days is one cycle of chemotherapy) for up to six cycles
* Ascorbate: 87.5 g administered intravenously (IV) twice each calendar week of the cycle
* Ferumoxytol: 512 g administered intravenously (IV) the first day of the first cycle of chemotherapy.

Radiation Phase

* Ascorbate: 87.5 g administered intravenously (IV) three times each calendar week for approximately 8 weeks.
* Ferumoxytol: 512 g administered intravenously (IV) the day before radiation, about 1 week after dose 1, during weeks 5 to 6 of radiation therapy, and then a week after that (for a total of 4 ferumoxytol infusions).
* Radiation: 61.2 Gray (given 1.8 Gray once daily, 5 days per week, for about 7 weeks) or 60 Gray (2.0 Gray once daily for 5 days per week for about 6 weeks)
* Temozolomide: 75 mg/m2, taken orally, once daily, every day, for up to 49 days or until radiation is completed (whichever comes first).

Adjuvant Phase

* Temozolomide: 150 to 200 mg/m2, taken orally, once daily, for five days out of 28 days (where 28 days is one cycle of chemotherapy) for up to six cycles
* Ascorbate: 87.5 g administered intravenously (IV) twice each calendar week of the cycle
* Ferumoxytol: 512 g administered intravenously (IV) the first day of the first cycle of

Ferumoxytol is an iron replacement product FDA approved for treatment of iron deficiency anemia in adult patients with chronic kidney disease (CKD). This trial uses the FDA approved dosage (512 mg iron) for iron-deficiency anemia in CKD.

Ferumoxytol injection

Pharmacological ascorbate

Photon based, focal radiation therapy delivered consistent with national guidelines, standard for treatment of GBM.

External beam radiation therapy

Temozolomide is a cytotoxic alkylating agent administered orally that penetrates well into the central nervous system. It is a standard-of-care treatment for GBM.

John M. Buatti, MD

This clinical trial evaluates adding ferumoxytol and pharamcologic ascorbate (vitamin C) to standard of care treatment of glioblastoma multiforme (a type of brain tumor) in adults. All subjects will receive ferumoxytol and pharmacologic ascorbate in addition to the standard treatment.

The initial, standard treatment for glioblastoma multiforme (GBM) involves maximum safe surgical resection followed by radiation combined with temozolomide (a chemotherapy pill you take by mouth).

Participants in this trial will:

* receive intravenous (IV) ferumoxytol the day before starting radiation, then around radiation treatments 6, 25, and 31.
* receive high doses of intravenous (IV) ascorbate three times a week during the combined radiation and chemotherapy phase.
* provide feedback about how they feel and their quality of life. This is done through short surveys as well as discussing with the study team.

A Safety Study of Pharmacologic Ascorbate and Ferumoxytol in Addition to Standard of Care Chemoradiation in Glioblastoma

A First-in-Human Clinical Trial of Pharmacologic Ascorbate and Ferumoxytol Combined With Concomitant Temozolomide and External Beam Radiation Therapy for Newly Diagnosed Glioblastoma

Data will be released publicly as per participant consent and IRB approval. Individual researchers should contact the research team for data sharing.

The recommended dose will be determined by incidence of dose limiting toxicities.

Time (measured in days) to documented disease progression in MRI imaging as described by the RANO criteria.

Objective response rate, measured using standardized RANO criteria, is a reflection of complete tumor response and partial tumor response. The radiation planning MRI will be used as baseline.

Tumor measurements completed as per RANO criteria and compared to the radiation-planning MRI (baseline)

Neurologic assessment in Neuro-Oncology (NANO) composite score evaluating gait, strength, ataxia, sensation, visual fields, facial strength, language, level of consciousness, and behavior and comparing to baseline.

Categorize and quantify adverse events using the Common Terminology Criteria for Adverse Events (v5)

Holden Comprehensive Cancer Center

National Cancer Institute (NCI)

Bryan Allen

Associate Professor

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Durvalumab

Antineoplastic Agents, Immunological

Two cycles of Durvalumab 1500 mg every 3 weeks, as monotherapy

Combination of pharmacological ascorbate 75 grams intravenously three times a week x 4 weeks plus Durvalumab 1500 mg every 3 weeks for two cycles

Serve as control and patients will not receive any neoadjuvant therapy before going to surgery. Once randomize, they can go to surgery without any delays.

Given intravenous (IV) infusion as monotherapy or in combination with pharmacological ascorbate

Given intravenously in combination with Durvalumab

Surgery (SOC)

Muhammad Furqan, MD

Alisha Demsky

This is a descriptive, proof of concept, open-label, randomized, 3-arm, window of opportunity trial to evaluate the immunomodulatory role of pharmacological ascorbate with Durvalumab

Participants in this research study have stage I Non-Small Cell Lung Cancer (NSCLC) that was found to be suitable for surgery as a first line treatment.

The usual treatment for this disease is to remove the tumor with surgery, and then evaluate after surgery if other additional treatments such as chemotherapy or targeted therapy are needed.

The purpose of this research study is to compare three different ways of treating stage 1 NSCLC, to see if adding treatment before surgery can reduce the chance of the tumor recurring after surgical removal.

In this study, patients will be randomly assigned to one of three treatments:

* Durvalumab followed by surgical resection of the tumor.
* Durvalumab plus ascorbate (also known as vitamin C), followed by surgical resection of the tumor.
* Surgical resection alone. No therapy prior to surgery. This is the same as standard care (SOC) for this disease.

This is a descriptive, proof of concept, open-label, randomized, 3-arm, window of opportunity trial to evaluate the immunomodulatory role of pharmacological ascorbate with Durvalumab. Translational and clinical findings of this study can then be applied more broadly to design and address clinically oriented questions in various NSCLC treatment settings.

Ascorbate With Durvalumab in Non-Small Cell Lung Cancer (NSCLC)

Assessing the Immunomodulatory Effects of Pharmacologic Ascorbate With Durvalumab (MEDI 4736) in Non-Small Cell Lung Cancer: A Window of Opportunity Trial

Determine if Pharmacological Ascorbate and durvalumab can potentiate or enhance an immune response in the NSCLC tumor-microenvironment compared to durvalumab alone. This will be evaluated in the surgically resected specimens of patients after receiving neoadjuvant therapy. CD8+ T cells will be quantified as the percentage of lymphocytes that are CD8+ T cells

Assess safety and tolerability of the combination of Pharmacological Ascorbate and Durvalumab in the neoadjuvant setting (Arm:2)

The proportion of patients with a pathologic complete response, defined as no viable tumor.

The proportion of patients with a major pathologic response, defined as residual viable tumor of 10% or less.

Time from randomization to progression of disease that precludes surgery, local or distant recurrence, or death due to any cause.

Time from randomization to death due to any cause.

Muhammad Furqan

Clinical Associate Professor

Digestive System Diseases

Gland and Hormone Related Diseases

Adenocarcinoma

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Gemcitabine

Paclitaxel

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Each cycle is 4 calendar weeks

Gemcitabine: 1000 mg/m2, once weekly for 3 weeks nab-paclitaxel: 125 mg/m2, once weekly for 3 weeks Pharmacological ascorbate: 75 grams, three times weekly for 4 weeks

Each cycle is 4 calendar weeks

Gemcitabine: 1000 mg/m2, once weekly for 3 weeks nab-paclitaxel: 125 mg/m2, once weekly for 3 weeks Each cycle has 1 rest week

Administered intravenously the same day as nab-paclitaxel and ascorbate Administered after nab-paclitaxel and before ascorbate

* given for 3 weeks out of the 4 week cycle
* standard dose reductions are used
* up to 2 cycles are administered before standard of care CT scan
* decision to continue therapy is based disease response to therapy as measured from the CT scan
* treatment continues until disease progression is identified

Administered intravenously the same day as nab-paclitaxel and ascorbate Administered after before gemcitabine and ascorbate

* given for 3 weeks out of the 4 week cycle
* standard dose reductions are used
* up to 2 cycles are administered before standard of care CT scan
* decision to continue therapy is based disease response to therapy as measured from the CT scan
* treatment continues until disease progression is identified

nab-paclitaxel

Administered intravenously the same day as nab-paclitaxel and gemcitabine Administered after nab-paclitaxel and gemcitabine

* given 3 times weekly
* given for 4 weeks out of the 4 week cycle
* no dose reductions are used
* up to 2 cycles are administered before standard of care CT scan
* decision to continue therapy is based disease response to therapy as measured from the CT scan
* treatment continues until disease progression is identified

Joseph J. Cullen, MD, FACS

This clinical trial adds high-dose ascorbate (vitamin C) to the standard of care regimen for metastatic pancreatic adenocarcinoma (a type of pancreatic cancer). Subjects are randomized between a control group (standard treatment) and an intervention group (pharmacologic ascorbate in addition to the standard treatment).

One of the standard treatments for metastatic pancreatic adenocarcinoma is nab-paclitaxel with gemcitabine. This standard therapy administers chemotherapy once per week for three weeks; patients then get a 'rest week' to complete the cycle (1 cycle = 4 weeks).

This study adds 75 grams of ascorbate (vitamin C, sometimes called pharamcological ascorbate because the dose is so high) to standard therapy. The ascorbate is administered intravenously - through a vein in the arm.

Participants in the control group will:

* receive gemcitabine and nab-paclitaxel chemotherapy, which is standard for their cancer.
* undergo imaging which is standard for their cancer and therapy. This can include CT scans, PET scans, and X-rays

Participants in the intervention group will:

* receive 75 grams of ascorbate 3 times per calendar week for each week of the chemotherapy cycle.
* undergo imaging which is standard for their cancer and therapy. This can include CT scans, PET scans, and X-rays
* provide blood samples to determine the biological effects, if any, the ascorbate has on the body during therapy.

This active therapy portion lasts until the disease progresses and a new treatment needs to be adopted - this can be months to years. If disease progresses, participants go back to standard follow-up for their caner and the new/additional therapy their doctors prescribe.

However, it is very important we remain in contact with participants; they will have life-long follow-up for this study.

A Phase 2 Trial of High-dose Ascorbate for Pancreatic Cancer (PACMAN 2.1)

A Phase II Trial of Pharmacological Ascorbate, Gemcitabine, and Nab-Paclitaxel for Metastatic Pancreatic Cancer (PACMAN 2.1)

Data will be shared per consent document, governing Federal regulations and institutional policies, and only after a signed sharing agreement between the sponsor and the requesting investigator.

Time, measured in months, from the start of chemotherapy (C1D1) to death from any cause.

Determine the objective response rate of the disease, assessed every 2 months using CT or MRI, and evaluated/defined using the RECIST criteria (v1.1). Results are provided in nominal categories (CR, PR, SD, PD) as per RECIST.

Time, measured in days, it takes disease to progress, where disease progression is defined by the RECIST criteria (v1.1). Timeframe is from radiation day 1 to date of disease progression.

Categorize and quantify adverse events using the Common Terminology Criteria for Adverse Events (CTCAE v4). Assessments will be monthly through 30 days past the end of therapy.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Safety Study of Pharmacologic Ascorbate and Ferumoxytol in Addition to Standard of Care Chemoradiation in Glioblastoma	NCT04900792	Glioblastoma Glioblastoma Mu...	Ferumoxytol inj... Pharmacological... External beam r... Temozolomide	18 Years -	University of Iowa
Ascorbate With Durvalumab in Non-Small Cell Lung Cancer (NSCLC)	NCT06083454	Non-small Cell ...	Durvalumab Pharmacological... Surgery (SOC)	18 Years -	University of Iowa
A Safety Study of Pharmacologic Ascorbate and Ferumoxytol in Addition to Standard of Care Chemoradiation in Glioblastoma	NCT04900792	Glioblastoma Glioblastoma Mu...	Ferumoxytol inj... Pharmacological... External beam r... Temozolomide	18 Years -	University of Iowa
A Phase 2 Trial of High-dose Ascorbate for Pancreatic Cancer (PACMAN 2.1)	NCT02905578	Pancreatic Neop... Cancer of Pancr... Cancer of the P... Neoplasms, Panc... Pancreas Cancer Pancreas Neopla... Adenocarcinoma	Gemcitabine nab-paclitaxel Pharmacological...	18 Years -	University of Iowa

Spots Global Cancer Trial Database for pharmacological ascorbate