Treatment of Radiation and Cisplatin Induced Toxicities with Tempol

NCT03480971 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: MBI-04-04
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 9

Brief Summary

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 cancer patients. Over the course of the 10 week trial, mucositis, nephrotoxicity, and ototoxicity will be monitored and assessed.

Conditions

Mucositis; Nephrotoxicity; Ototoxicity

Keywords

cisplatin toxicity

Outcome Measures

Primary Outcomes (1)

• Mucositis

  To determine the efficacy of Tempol in reducing the incidence severe mucositis defined as grade 3 or 4 on the World Health Organization (WHO) scale. The incidence will measure the number of patients who experience grade 3 or 4 mucositis according to the World Health Organization (WHO) scale. A reduction in the number of patients who receive grade 3 or 4 mucositis over the course of the treatment is considered a positive change in incidence.

  10 weeks

Secondary Outcomes (4)

• Mucositis

  10 weeks

• Nephrotoxicity

  10 weeks

• Nephrotoxicity

  10 weeks

• Mucositis

  10 weeks

Study Arms (2)

Active 1000 mg Tempol Solution

ACTIVE COMPARATOR

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

Drug: Tempol

Placebo Solution

PLACEBO COMPARATOR

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

Drug: Placebo Solution

Interventions

Tempol DRUG

Investigational product is Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) oral solution. Tempol solution is an orange-colored, aqueous solution containing 7% Tempol along with xanthan gum, xylitol, aspartame, acesulfame potassium, sodium saccharin, alcohol, peppermint and wintergreen oils.

Also known as: 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl

Active 1000 mg Tempol Solution

Placebo Solution DRUG

The placebo contains the same excipients as the active product plus FD\&C Yellow #6 for color matching.

Placebo Solution

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be ≥18 years of age with medically diagnosed squamous cell cancer of the head and neck (SCCHN);
• Be scheduled to receive radiotherapy or proton therapy administered with a curative intent;
• If female and of child bearing potential, be using an effective birth-control method with a history of reliability for the individual participant;
• If male and of child bearing potential, adequate methods of contraception must be employed including use of condoms with spermicide. No sperm donation for 90 days until after the conclusion of the study;
• Must be receiving cisplatin for chemotherapy;
• Be properly informed of the nature and risks of the clinical investigation, comply with all clinical investigation-related procedures, and sign an Informed Consent Form prior to entering the clinical investigation;
• Must have a score 2 or less on the ECOG performance status;
• Participant life expectancy ≥ 6 months; and
• Adequate baseline organ function (hematologic, liver, renal, nutritional and metabolic):
• Haematology:
• Absolute neutrophil count (ANC) ≥1.5 Hemoglobin ≥ 10 g/dL Platelets ≥ 100,000 per microliter of blood
• Hepatic:
• Total bilirubin ≤ 2 X (Upper limit normal) ULN Alanine amino transferase (ALT) and Aspartate aminotransferase (AST) ≤5 x ULN
• Renal:
• Serum creatinine ≤ ULN or, if \> ULN calculated creatinine clearance (CrCl) ≥ 60 mL/min.

You may not qualify if:

• Prior radiotherapy of the head and neck;
• Have a clinically significant infection defined as any acute viral, bacterial or fungal infection, which requires specific therapy. Anti-infectious therapy must have been completed within 14 days of starting study treatment;
• Be taking any non-approved therapy for oral mucositis, including β-carotene, tocopherol, laser irradiation, brushing the oral mucosa with silver-nitrate prophylactically, systemic TGF-β (transforming growth factor beta), or systemic KGF (keratinocyte growth factor) during or within 14 days of starting treatment;
• Be taking mugard;
• Be taking prostaglandins, pentoxifylline or leucovorin during or within 14 days of starting treatment;
• Be rinsing with allopurinol, hydrogen peroxide, sucralfate, or chlorhexidine mouthwashes during or within 14 days of starting treatment;
• Have had a recent, serious, non-malignant medical complication that, in the opinion of the investigator, makes the individual unsuitable for study participation;
• Have used an investigational drug within 28 days of the initiation of study treatment;
• Have a history of a positive blood test for HIV;
• At the time of screening, having a significant active medical illness which, in the opinion of the investigator, would preclude completion of the study;
• Participants with a treatment plan consisting of chemoradiation followed by further chemotherapy;
• Participants with body weight less than 35 kg, 77 lbs;
• Women who are pregnant or who are breastfeeding;
• Participants with known intolerance to platin drugs;
• History of insulin-dependent Diabetes Mellitus; and

Sponsors & Collaborators

• Matrix Biomed, Inc.: lead

Study Sites (9)

UCSD

La Jolla, California, 92093, United States

RECRUITING

Mercy Medical Center

Merced, California, 95340, United States

RECRUITING

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94158, United States

ACTIVE NOT RECRUITING

Central Coast Medical Oncology

Santa Maria, California, 93454, United States

RECRUITING

Mission Hope Health Center

Santa Maria, California, 93454, United States

RECRUITING

Montefiore Medical Center-Einstein Campus

The Bronx, New York, 10461, United States

RECRUITING

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

RECRUITING

Seattle Cancer Care Alliance

Seattle, Washington, 98195, United States

RECRUITING

University of Washington Medical Center

Seattle, Washington, 98195, United States

RECRUITING

Related Publications (9)

• Arany I, Safirstein RL. Cisplatin nephrotoxicity. Semin Nephrol. 2003 Sep;23(5):460-4. doi: 10.1016/s0270-9295(03)00089-5.

  PMID: 13680535 BACKGROUND

• Ahmed LA, Shehata NI, Abdelkader NF, Khattab MM. Tempol, a superoxide dismutase mimetic agent, ameliorates cisplatin-induced nephrotoxicity through alleviation of mitochondrial dysfunction in mice. PLoS One. 2014 Oct 1;9(10):e108889. doi: 10.1371/journal.pone.0108889. eCollection 2014.

  PMID: 25271439 BACKGROUND

• Scully C, Sonis S, Diz PD. Oral mucositis. Oral Dis. 2006 May;12(3):229-41. doi: 10.1111/j.1601-0825.2006.01258.x.

  PMID: 16700732 BACKGROUND

• Hartmann JT, Lipp HP. Toxicity of platinum compounds. Expert Opin Pharmacother. 2003 Jun;4(6):889-901. doi: 10.1517/14656566.4.6.889.

  PMID: 12783586 BACKGROUND

• Sastry J, Kellie SJ. Severe neurotoxicity, ototoxicity and nephrotoxicity following high-dose cisplatin and amifostine. Pediatr Hematol Oncol. 2005 Jul-Aug;22(5):441-5. doi: 10.1080/08880010590964381.

  PMID: 16020136 BACKGROUND

• Samuni A, Winkelsberg D, Pinson A, Hahn SM, Mitchell JB, Russo A. Nitroxide stable radicals protect beating cardiomyocytes against oxidative damage. J Clin Invest. 1991 May;87(5):1526-30. doi: 10.1172/JCI115163.

  PMID: 1850756 BACKGROUND

• Samuni A, Mitchell JB, DeGraff W, Krishna CM, Samuni U, Russo A. Nitroxide SOD-mimics: modes of action. Free Radic Res Commun. 1991;12-13 Pt 1:187-94. doi: 10.3109/10715769109145785.

  PMID: 1649088 BACKGROUND

• Samuni A, Krishna CM, Mitchell JB, Collins CR, Russo A. Superoxide reaction with nitroxides. Free Radic Res Commun. 1990;9(3-6):241-9. doi: 10.3109/10715769009145682.

  PMID: 2167262 BACKGROUND

• Mitchell JB, Anver MR, Sowers AL, Rosenberg PS, Figueroa M, Thetford A, Krishna MC, Albert PS, Cook JA. The antioxidant tempol reduces carcinogenesis and enhances survival in mice when administered after nonlethal total body radiation. Cancer Res. 2012 Sep 15;72(18):4846-55. doi: 10.1158/0008-5472.CAN-12-1879. Epub 2012 Jul 17.

  PMID: 22805306 BACKGROUND

MeSH Terms

Conditions

Mucositis; Ototoxicity

Interventions

tempol

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Mouth Diseases; Stomatognathic Diseases; Ear Diseases; Otorhinolaryngologic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Radiation Injuries; Wounds and Injuries

Study Officials

• Benji Crane

  Matrix Biomed, Inc.

  STUDY DIRECTOR

Central Study Contacts

Benji Crane

CONTACT

6264376506; bjcrane@matrixbiomed.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2018
• First Posted: March 29, 2018
• Study Start: May 13, 2019
• Primary Completion: July 1, 2025
• Study Completion: December 1, 2025
• Last Updated: November 20, 2024

Record last verified: 2024-11

Locations

US (9)