Tempol for Treatment Toxicities

Recruiting at8 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Trial Summary

What is the purpose of this trial?

This trial tests Tempol in head and neck cancer patients to see if it can reduce side effects from radiation and chemotherapy. Tempol protects healthy cells but not cancer cells, potentially reducing issues like mouth sores, kidney damage, and hearing loss.

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.

What data supports the effectiveness of the drug Tempol for treatment toxicities?

Research shows that Tempol can protect salivary glands during radiation therapy, reduce inflammation, and decrease sickness behavior in mice. It also has potential anti-cancer properties and can lower blood pressure by widening blood vessels. ^{1 2 3 4 5}

How does the drug Tempol differ from other treatments for treatment toxicities?

Tempol is unique because it is being studied for its potential to reduce treatment-related toxicities, which may not be the primary focus of other treatments. While the research does not provide direct information about Tempol, it highlights the importance of considering excipients (inactive ingredients) in medications, which can sometimes cause side effects. This suggests that Tempol might be formulated to minimize such issues, making it potentially safer or more tolerable compared to other treatments. ^{6 7 8 9 10}

Research Team

Benji Crane

Principal Investigator

Matrix Biomed, Inc.

Eligibility Criteria

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

I am 18 or older with a diagnosis of head and neck cancer.

Urine Albumin < 3.0 mg/dl

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

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.

Trial Timeline

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)

Treatment Details

Interventions

• Placebo Solution (Chemotherapy)
• Tempol (Free Radical Scavenger)

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Kinetics of tempol for prevention of xerostomia following head and neck irradiation in a mouse model. [2015]

2. England pubmed.ncbi.nlm.nih.gov

Tempol modulates the leukocyte response to inflammatory stimuli and attenuates endotoxin-induced sickness behaviour in mice. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Nitroxide tempo, a small molecule, induces apoptosis in prostate carcinoma cells and suppresses tumor growth in athymic mice. [2007]

4. United States pubmed.ncbi.nlm.nih.gov

Hemodynamic effect of the nitroxide superoxide dismutase mimics. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Tempol differential effect on prostate cancer inflammation: In vitro and in vivo evaluation. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Gastrointestinal effects of sorbitol as an additive in liquid medications. [2022]

7. England pubmed.ncbi.nlm.nih.gov

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

8. Netherlands pubmed.ncbi.nlm.nih.gov

Excipients in medicinal products used in gastroenterology as a possible cause of side effects. [2013]

9. Poland pubmed.ncbi.nlm.nih.gov

Comparison of sublingual tablets with nitroglycerin complexed with beta-cyclodextrin or titrated with crosspovidone--technological approach. [2013]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Endocrine Effects of an Oral Dose of D-Pinitol in Human Fasting Healthy Volunteers. [2022]