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Treatment of Radiation and Cisplatin Induced Toxicities With Tempol

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ClinicalTrials.gov Identifier: NCT03480971
Recruitment Status : Recruiting
First Posted : March 29, 2018
Last Update Posted : February 18, 2022
Sponsor:
Information provided by (Responsible Party):
Matrix Biomed, Inc.

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.

Condition or disease Intervention/treatment Phase
Mucositis Nephrotoxicity Ototoxicity Drug: Tempol Drug: Placebo Solution Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Double Blind, Placebo Controlled Dose Range Finding Study to Assess the Safety, Pharmacokinetics, and Efficacy of Tempol for the Reduction of Severe Mucositis in Head and Neck Cancer Patients Undergoing Combined Radio- and Chemotherapy
Actual Study Start Date : May 13, 2019
Estimated Primary Completion Date : January 2023
Estimated Study Completion Date : April 2023

Arm Intervention/treatment
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
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.
Other Name: 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl

Placebo Comparator: Placebo Solution
Patients will take placebo solution everyday for the duration of radiation treatment (6-8 weeks)
Drug: Placebo Solution
The placebo contains the same excipients as the active product plus FD&C Yellow #6 for color matching.




Primary Outcome Measures :
  1. Mucositis [ Time Frame: 10 weeks ]

    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.



Secondary Outcome Measures :
  1. Mucositis [ Time Frame: 10 weeks ]

    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.


  2. Nephrotoxicity [ Time Frame: 10 weeks ]
    Reduction in Serum Creatinine levels in active arm versus placebo arm.

  3. Nephrotoxicity [ Time Frame: 10 weeks ]
    Reduction in Blood Urea Nitrogen levels in active arm versus placebo arm.

  4. Mucositis [ Time Frame: 10 weeks ]

    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.




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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:

  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03480971


Contacts
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Contact: Benji Crane 6264376506 bjcrane@matrixbiomed.com

Locations
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United States, California
UCSD Recruiting
La Jolla, California, United States, 92093
Mercy Medical Center Recruiting
Merced, California, United States, 95340
UCSF Helen Diller Family Comprehensive Cancer Center Active, not recruiting
San Francisco, California, United States, 94158
Central Coast Medical Oncology Recruiting
Santa Maria, California, United States, 93454
Mission Hope Health Center Recruiting
Santa Maria, California, United States, 93454
United States, New York
Montefiore Medical Center-Einstein Campus Recruiting
Bronx, New York, United States, 10461
United States, North Carolina
Wake Forest University Health Sciences Recruiting
Winston-Salem, North Carolina, United States, 27157
United States, Washington
Seattle Cancer Care Alliance Recruiting
Seattle, Washington, United States, 98195
University of Washington Medical Center Recruiting
Seattle, Washington, United States, 98195
Sponsors and Collaborators
Matrix Biomed, Inc.
Investigators
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Study Director: Benji Crane Matrix Biomed, Inc.
Publications:

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Responsible Party: Matrix Biomed, Inc.
ClinicalTrials.gov Identifier: NCT03480971    
Other Study ID Numbers: MBI-04-04
First Posted: March 29, 2018    Key Record Dates
Last Update Posted: February 18, 2022
Last Verified: February 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Matrix Biomed, Inc.:
cisplatin toxicity
Additional relevant MeSH terms:
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Mucositis
Ototoxicity
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Mouth Diseases
Stomatognathic Diseases
Ear Diseases
Otorhinolaryngologic Diseases
Pathologic Processes
Drug-Related Side Effects and Adverse Reactions
Chemically-Induced Disorders
Radiation Injuries
Wounds and Injuries
Tempol
TEMPO
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Protein Synthesis Inhibitors
Enzyme Inhibitors
Radiation-Protective Agents
Neuroprotective Agents