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RecruitingNCT03480971Updated Nov 20, 2024

Treatment of Radiation and Cisplatin Induced Toxicities with Tempol

A Phase 2 interventional study of Tempol and Placebo Solution in Mucositis, Nephrotoxicity and Ototoxicity, sponsored by Matrix Biomed, Inc.. Recruiting at 9 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-11-20.

Sponsored by Matrix Biomed, Inc. · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
120
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the detailed description

One hundred and twenty (120) participants with head and neck cancer are scheduled to undergo combined radio- and chemotherapy (n = 120).

Nearly all (90% to 97%) participants receiving radiotherapy in the head and neck will develop some degree of mucositis. Of these participants treated with radiotherapy with or without chemotherapy, 34% to 43% will present severe mucositis. As a result, the participant's quality of life is affected, hospital admittance rates are higher, the use of total parenteral nutrition is increased and interruption of treatment is more frequent, all of which compromise tumor control. Mucositis causes 9% to 19% of chemotherapy and radiotherapy interruption.

A common chemotherapeutic agent used in head and neck cancer is Cisplatin. Cisplatin (cis- diamminedichloroplatinum(II), CDDP) is an antineoplastic drug used in the treatment of many cancers including testicular cancer, ovarian cancer, bladder cancer, head and neck cancer, esophageal cancer, small and non-small cell lung cancer, breast cancer, cervical cancer, stomach cancer, prostate cancer, brain tumors, neuroblastoma, sarcomas, multiple myeloma, melanoma, mesothelioma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, pancreatic cancer, and thyroid cancer. While toxicities include ototoxicity, gastrotoxicity, myelosuppression, and allergic reactions, the main dose-limiting side effect of cisplatin is nephrotoxicity followed by ototoxicity.

Tempol is a piperidine nitroxide. Nitroxides are a class of stable free radical compounds that protects mammalian cells against numerous toxic agents. Tempol protects normal cells from radiation and cisplatin-induced damage; however, in cancerous or tumor cells, Tempol is reduced to its hydroxylamine form that does not and cannot protect the cells from radiation and cisplatin induced damage. This distinction is of particular importance in the setting of cancer treatment, in which both normal and tumor tissue is exposed to radiation and chemotherapy.

Without using Tempol, both normal cells and cancer cells suffer from toxicity. Tempol is the only known compound to possess this functional duality. This compound has the potential to prevent many of the toxicities associated with cisplatin and radiation treatment including the prevention of mucositis, nephrotoxicity, and ototoxicity.

02

Conditions studied

  • Mucositis
  • Nephrotoxicity
  • Ototoxicity

Keywords

  • cisplatin toxicity
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Be ≥18 years of age with medically diagnosed squamous cell cancer of the head and neck (SCCHN);
  2. Be scheduled to receive radiotherapy or proton therapy administered with a curative intent;
  3. If female and of child bearing potential, be using an effective birth-control method with a history of reliability for the individual participant;
  4. 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;
  5. Must be receiving cisplatin for chemotherapy;
  6. 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;
  7. Must have a score 2 or less on the ECOG performance status;
  8. Participant life expectancy ≥ 6 months; and
  9. 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.

Nutritional and metabolic:

Urine Albumin \< 3.0 mg/dl

Exclusion criteria

Exclusion Criteria:

  1. Prior radiotherapy of the head and neck;
  2. 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;
  3. 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;
  4. Be taking mugard;
  5. Be taking prostaglandins, pentoxifylline or leucovorin during or within 14 days of starting treatment;
  6. Be rinsing with allopurinol, hydrogen peroxide, sucralfate, or chlorhexidine mouthwashes during or within 14 days of starting treatment;
  7. Have had a recent, serious, non-malignant medical complication that, in the opinion of the investigator, makes the individual unsuitable for study participation;
  8. Have used an investigational drug within 28 days of the initiation of study treatment;
  9. Have a history of a positive blood test for HIV;
  10. At the time of screening, having a significant active medical illness which, in the opinion of the investigator, would preclude completion of the study;
  11. Participants with a treatment plan consisting of chemoradiation followed by further chemotherapy;
  12. Participants with body weight less than 35 kg, 77 lbs;
  13. Women who are pregnant or who are breastfeeding;
  14. Participants with known intolerance to platin drugs;
  15. History of insulin-dependent Diabetes Mellitus; and
  16. Participants with Hepatitis B/C.
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
120 participants (estimated)

Study arms

  • Active comparator
    Active 1000 mg Tempol Solution

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

    Drug: Tempol

  • Placebo comparator
    Placebo Solution

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

    Drug: Placebo Solution

Interventions

  • DrugTempol

    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

  • DrugPlacebo Solution

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

05

What researchers measure

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.

    Time frame: 10 weeks

Secondary outcomes

  1. Mucositis

    To determine the efficacy of Tempol in reducing the duration severe mucositis defined as grade 3 or 4 on the World Health Organization (WHO) scale. This duration will be measured by total number of days number a patient experiences grade 3 or 4 mucositis according to the World Health Organization (WHO) scale. A reduction in the total number of days a patient receives grade 3 or 4 mucositis over the course of the treatment is considered a positive change in duration.

    Time frame: 10 weeks

  2. Nephrotoxicity

    Reduction in Serum Creatinine levels in active arm versus placebo arm.

    Time frame: 10 weeks

  3. Nephrotoxicity

    Reduction in Blood Urea Nitrogen levels in active arm versus placebo arm.

    Time frame: 10 weeks

  4. Mucositis

    To determine the efficacy of Tempol in reducing the time to onset of grades 1-4 mucositis on the World Health Organization (WHO) scale. This time to onset will measure the number of days after exposure to cisplatin before a patient experiences grade 1 through 4 mucositis according to the World Health Organization (WHO) scale. An increase in the total number of days before a patient receives grade 1 through 4 mucositis after cisplatin exposure is considered a positive change in time to onset.

    Time frame: 10 weeks

06

Study locations

8 of 9 sites recruiting
  • 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
    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
07

References and documents

Publications

  • Arany I, Safirstein RL. Cisplatin nephrotoxicity. Semin Nephrol. 2003 Sep;23(5):460-4. doi: 10.1016/s0270-9295(03)00089-5. PubMed 13680535 ↗
  • 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. Erratum In: PLoS One. 2014;9(12):e115983. PubMed 25271439 ↗
  • 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. PubMed 16700732 ↗
  • Hartmann JT, Lipp HP. Toxicity of platinum compounds. Expert Opin Pharmacother. 2003 Jun;4(6):889-901. doi: 10.1517/14656566.4.6.889. PubMed 12783586 ↗
  • 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. PubMed 16020136 ↗
  • 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. PubMed 1850756 ↗
  • 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. PubMed 1649088 ↗
  • 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. PubMed 2167262 ↗
  • 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. PubMed 22805306 ↗

Individual participant data

Plan to share: Undecided

08

Registry details

Key details

Study ID
NCT03480971
Lead sponsor
Matrix Biomed, Inc.
Responsible party
Sponsor
First posted
Mar 29, 2018
Start date
May 13, 2019
Primary completion
Jul 2025 (estimated)
Completion
Dec 2025 (estimated)
Last update
Nov 20, 2024

Study contacts

Benji Crane
Contact
bjcrane@matrixbiomed.com
6264376506
Benji Crane
study director · Matrix Biomed, Inc.

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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