Treatment of Radiation and Cisplatin Induced Toxicities with Tempol

November 18, 2024 updated by: Matrix Biomed, Inc.

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

120

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • La Jolla, California, United States, 92093
        • Recruiting
        • UCSD
      • Merced, California, United States, 95340
        • Recruiting
        • Mercy Medical Center
      • San Francisco, California, United States, 94158
        • Active, not recruiting
        • UCSF Helen Diller Family Comprehensive Cancer Center
      • Santa Maria, California, United States, 93454
        • Recruiting
        • Central Coast Medical Oncology
      • Santa Maria, California, United States, 93454
        • Recruiting
        • Mission Hope Health Center
    • New York
      • Bronx, New York, United States, 10461
        • Recruiting
        • Montefiore Medical Center-Einstein Campus
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157
        • Recruiting
        • Wake Forest University Health Sciences
    • Washington
      • Seattle, Washington, United States, 98195
        • Recruiting
        • University of Washington Medical Center
      • Seattle, Washington, United States, 98195
        • Recruiting
        • Seattle Cancer Care Alliance

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / 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 Names:
  • 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
10 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
10 weeks
Nephrotoxicity
Time Frame: 10 weeks
Reduction in Serum Creatinine levels in active arm versus placebo arm.
10 weeks
Nephrotoxicity
Time Frame: 10 weeks
Reduction in Blood Urea Nitrogen levels in active arm versus placebo arm.
10 weeks
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.
10 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Matrix Biomed, Inc.

Investigators

  • Study Director: Benji Crane, Matrix Biomed, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 13, 2019

Primary Completion (Estimated)

July 1, 2025

Study Completion (Estimated)

December 1, 2025

Study Registration Dates

First Submitted

March 8, 2018

First Submitted That Met QC Criteria

March 27, 2018

First Posted (Actual)

March 29, 2018

Study Record Updates

Last Update Posted (Actual)

November 20, 2024

Last Update Submitted That Met QC Criteria

November 18, 2024

Last Verified

November 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MBI-04-04

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Mucositis

Clinical Trials on Tempol

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Costa Rica

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe