Tempol for Treatment Toxicities

Recruiting at 9 trial locations

Overseen By Benji Crane

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Matrix Biomed, Inc.

Must be taking: Cisplatin

Must not be taking: Prostaglandins, Pentoxifylline, Leucovorin, others

Disqualifiers: Prior radiotherapy, HIV, Diabetes, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 6-8 weeks

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates whether Tempol can reduce the side effects of certain cancer treatments. Specifically, it examines if Tempol can prevent or lessen mouth sores, kidney issues, and ear damage in individuals with head and neck cancers receiving cisplatin and radiation therapy. Participants will receive either Tempol or a placebo (an inactive substance) during their radiation treatment to evaluate its effectiveness. Eligible participants have squamous cell cancer of the head and neck and are scheduled for radiation therapy with cisplatin chemotherapy. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as non-approved therapies for oral mucositis, specific mouthwashes, and some other drugs, at least 14 days before starting the treatment. If you are on any of these, you will need to stop them before participating.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study showed that Tempol can reduce inflammation and protect the kidneys. It acts as a "radical scavenger," neutralizing harmful molecules in the body. However, safety is a concern. Some reports suggest that Tempol can cause serious eye and skin damage, so careful handling is necessary.

The current trial is in Phase 2, indicating that Tempol has already been tested in smaller groups. At this stage, researchers are generally confident about the treatment's basic safety. They continue to study its effects and assess tolerance. Earlier studies have not identified major safety concerns, but ensuring safety remains a key focus in ongoing research. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Tempol because it offers a unique approach to managing radiation treatment toxicities. Unlike traditional treatments that primarily focus on symptomatic relief, Tempol works by actively reducing oxidative stress in the body, which is a key factor in radiation-induced damage. This antioxidant effect not only aims to minimize side effects but also potentially enhances the overall effectiveness of radiation therapy by protecting healthy cells. With its novel mechanism of action, Tempol could represent a significant advancement in supportive care for patients undergoing radiation.

What evidence suggests that Tempol could be effective in reducing treatment toxicities for head and neck cancer?

Research has shown that Tempol, which participants in this trial may receive, might help lessen the side effects of treatments like radiation and chemotherapy. Studies have found that Tempol can protect cells by neutralizing harmful molecules. Tests demonstrated that Tempol reduced tissue damage and successfully protected nerve cells from harmful substances. These findings suggest that Tempol could potentially reduce harmful side effects such as painful mouth inflammation, kidney damage, and hearing damage in patients undergoing cancer treatments. ^{6 7 8 9 10}

Who Is on the Research Team?

Benji Crane

Principal Investigator

Matrix Biomed, Inc.

Are You a Good Fit for This Trial?

This trial is for adults over 18 with squamous cell cancer of the head and neck, undergoing cisplatin chemotherapy and radiotherapy. They must have good kidney function, not be pregnant or breastfeeding, use effective birth control if applicable, and not have a history of certain conditions like HIV or insulin-dependent diabetes.

Inclusion Criteria

Urine Albumin < 3.0 mg/dl

I am a man who can father children and will use condoms with spermicide during the study.

My blood, liver, kidney, and overall health are good.

Exclusion Criteria

Have had a recent, serious, non-malignant medical complication that, in the opinion of the investigator, makes the individual unsuitable for study participation;

I have Hepatitis B or C.

I have no ongoing infections requiring treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either 1000 mg Tempol or placebo daily during radiation treatment

6-8 weeks

Weekly visits for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

2-4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Placebo Solution
• Tempol

Trial Overview The study tests Tempol's effectiveness in preventing/reducing side effects from cisplatin and radiation therapy in head and neck cancer patients. Over 10 weeks, it will compare Tempol to a placebo solution while monitoring mucositis (mouth sores), kidney damage, and hearing loss.

How Is the Trial Designed?

Group I: Active 1000 mg Tempol Solution Active Control 1 Intervention

Patients will take 1000 mg of Tempol a day for the duration of radiation treatment (6-8 weeks)

Group II: Placebo Solution Placebo Group 1 Intervention

Patients will take placebo solution everyday for the duration of radiation treatment (6-8 weeks)

Who Is Running the Clinical Trial?

Matrix Biomed, Inc.

Lead Sponsor

Trials

6

Recruited

250+

Published Research Related to This Trial

Tempol, a nitroxide compound, demonstrated dose-related hypotension and increased skin temperature in miniature swine, indicating its potent vasodilative effects and potential as a treatment for oxidative stress.

In contrast, another nitroxide, 3-carbamoyl-PROXYL (3-CP), did not affect blood pressure, suggesting that different nitroxides may have varying impacts on vascular function and nitric oxide levels, which could influence their therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemodynamic effect of the nitroxide superoxide dismutase mimics. Hahn, SM., Sullivan, FJ., DeLuca, AM., et al.[2019]

Sorbitol, a common sugar alcohol used in liquid oral medications, can cause gastrointestinal side effects like diarrhea, highlighting the need for awareness of its effects as an excipient.

A study of 142 products revealed challenges in obtaining accurate sorbitol content information from manufacturers, suggesting that pharmaceutical companies should be more transparent about inert ingredients to help healthcare providers manage patient symptoms effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastrointestinal effects of sorbitol as an additive in liquid medications. Johnston, KR., Govel, LA., Andritz, MH.[2022]

The study found that the physical stability of atenolol tablets can be negatively affected by storage in compliance aids, particularly at room temperature, with one brand showing reduced hardness when stored in a specific compliance aid (Dosett).

Despite the physical changes observed, the chemical stability and bioavailability of atenolol were not significantly impacted, suggesting that while appearance and texture may change, the effectiveness of the medication remains intact under the tested conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality of medicines stored together in multi-compartment compliance aids. Donyai, P.[2022]

D-Pinitol, a natural insulin mimetic, is effectively absorbed orally in healthy volunteers, showing a dose-dependent absorption with a peak concentration (Tmax) reached around 4 hours after ingestion and a half-life greater than 5 hours.

At a dose of 15 mg/kg, D-Pinitol did not raise glucose levels but reduced insulin and increased glucagon and ghrelin, suggesting its potential role in protecting the endocrine pancreas and possibly aiding in the prevention of insulin resistance-related conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Endocrine Effects of an Oral Dose of D-Pinitol in Human Fasting Healthy Volunteers. Navarro, JA., Díaz, C., Decara, J., et al.[2022]

Tempol significantly reduces radiation-induced damage to salivary glands, with a 50-60% improvement in salivary function when administered before irradiation in mice.

Both intravenous and subcutaneous routes of tempol administration were effective in providing radioprotection, and topical applications (mouthwash or gel) also showed promising results, indicating its potential for clinical use in patients receiving head and neck radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kinetics of tempol for prevention of xerostomia following head and neck irradiation in a mouse model. Cotrim, AP., Sowers, AL., Lodde, BM., et al.[2015]

Tempol demonstrated significant anti-inflammatory and antiproliferative effects in prostate cancer models, reducing tumor progression and improving prostatic morphology in both hormone-dependent and hormone-independent cell lines.

The study found that tempol modulates inflammatory signaling by downregulating NF-κB and TNF-α levels, indicating its potential as a beneficial therapy for prostate cancer treatment, with effects varying based on the stage of cancer and hormone dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tempol differential effect on prostate cancer inflammation: In vitro and in vivo evaluation. Rossetto, I., Santos, F., Kido, L., et al.[2023]

Fast disintegrating sublingual tablets with nitroglycerin complexed with beta-cyclodextrin (NTG-CD) showed better stability and disintegration time compared to those with nitroglycerin titrated with crosspovidone (NTG-CP).

Despite the improved stability of NTG in NTG-CD tablets, all formulations experienced a loss of over 10% of nitroglycerin within 12 months at room temperature, indicating a need for careful storage and handling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of sublingual tablets with nitroglycerin complexed with beta-cyclodextrin or titrated with crosspovidone--technological approach. Centkowska, K., Sznitowska, M.[2013]

The review identified 11 excipients commonly found in oral gastrointestinal products in Italy that may impact safety, including sucrose, aspartame, and lactose, highlighting the need for awareness of their potential adverse effects.

There were no significant differences in excipient content among products marketed in Italy, the UK, and the USA, but UK and USA product labels provided more detailed safety warnings, indicating a need for improved labeling in Italy to aid healthcare professionals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Excipients in medicinal products used in gastroenterology as a possible cause of side effects. Ursino, MG., Poluzzi, E., Caramella, C., et al.[2013]

Tempol significantly reduced the respiratory burst of neutrophils primed with lipopolysaccharide (LPS), indicating its potential to modulate immune responses to endotoxins.

In mice, Tempol pretreatment decreased sickness behavior and inhibited leukocyte migration after LPS exposure, suggesting it may have therapeutic benefits in managing inflammation and sickness responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tempol modulates the leukocyte response to inflammatory stimuli and attenuates endotoxin-induced sickness behaviour in mice. Lima, SNP., Cerdeira, CD., Santos, GB., et al.[2021]

Nitroxide tempo significantly induced apoptosis in prostate carcinoma cells, with increases in apoptotic cells observed up to 12-fold in certain cell lines, and activated caspase-9 and caspase-3 signaling pathways, indicating a strong mechanism of action against cancer cells.

In vivo studies showed that tempo treatment led to a significant reduction in tumor growth in mice with LNCaP tumors, suggesting its potential as an effective antineoplastic agent when used alone or in combination with other chemotherapy drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nitroxide tempo, a small molecule, induces apoptosis in prostate carcinoma cells and suppresses tumor growth in athymic mice. Suy, S., Mitchell, JB., Samuni, A., et al.[2007]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03480971

Study Details | NCT03480971 | Treatment of Radiation and ... A 10 week trial to assess the ability of Tempol to prevent and/or reduce toxicities associated with cisplatin and radiation treatment in head and neck ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10294991/

Efficacy of the Radical Scavenger, Tempol, to Reduce ... Our results demonstrated the ability of tempol, at the highest percentages, to counteract AD by reducing the histological damage, decreasing ...

3. aacrjournals.org aacrjournals.org/clincancerres/article/10/19/6411/183397/A-Phase-I-Study-of-Topical-Tempol-for-the

A Phase I Study of Topical Tempol for the Prevention of ... There was no change in the side effect profile after the change in application of Tempol. Hair loss/growth data scored by the investigator are shown in Table 5 ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7332214/

Prevention and treatment of radiotherapy‐induced side effects We discuss these consequences, focusing on their implications for the prevention and treatment of radiation‐induced side effects.

5. sciencedirect.com sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/tempol

Tempol - an overview Tempol has been reported effective in protecting neuronal cells against ischemic and toxic challenges in several models. It has been found to reduce the ...

6. sigmaaldrich.com sigmaaldrich.com/sds/aldrich/176141?srsltid=AfmBOoq4FVtw031TPoihBzvliIZr_ldIl214FDSSV5rta86gBTJdR9WN

SAFETY DATA SHEET 4-Hydroxy-TEMPO is harmful if swallowed, causes serious eye damage, may cause organ damage, and is harmful to aquatic life. Do not breathe dust.

7. fishersci.com fishersci.com/store/msds?partNumber=AC175050050&productDescription=4-HYDROXY-2%2C2%2C6%2C6-TETRAM+5GR&vendorId=VN00032119&countryCode=US&language=en

SAFETY DATA SHEET This product does not contain any hazardous materials with occupational exposure limitsestablished by the region specific regulatory bodies.

8. carlroth.com carlroth.com/downloads/sdb/en/6/SDB_6801_IE_EN.pdf

Safety Data Sheet: 2,2,6,6-Tetramethylpiperidine-1-oxyl This substance causes severe skin burns and eye damage, is a skin corroder, and can cause irreversible skin damage. It is also combustible.

9. pubchem.ncbi.nlm.nih.gov pubchem.ncbi.nlm.nih.gov/compound/Tempol

Tempol | C9H18NO2 | CID 137994 - PubChem - NIH It is a radical scavenger which exhibits anti-inflammatory and analgesic properties. It has a role as a radical scavenger, a catalyst, a nephroprotective agent.

10. chemicalbook.com chemicalbook.com/ChemicalProductProperty_EN_CB5782374.htm

4-Hydroxy-2,2,6,6-tetramethyl-piperidinooxy | 2226-96-2 TEMPOL (1 mM) inhibits production of superoxide anions by 92% via a xanthine-xanthine oxidase reaction in vitro. It reduces mean arterial pressure and heart ...