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Trial record 16 of 174 for:    The University of Kansas Cancer Center | Recruiting, Not yet recruiting, Available Studies

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 : June 10, 2019
Sponsor:
Collaborator:
University of Maryland, College Park
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 have anti-oxidant activity protecting mammalian cells against numerous toxic agents including hydrogen peroxide, superoxide, and t-butyl hydroperoxide cytotoxicity. This anti-oxidant activity of Tempol has led to its investigation as a potential radioprotector and chemoprotectant. In radiation and chemotherapy, 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. Because of Tempol's free-radical scavenging ability, this compound is able to prevent many of the toxicities associated with cisplatin and radiation treatment including the prevention of mucositis, nephrotoxicity, and ototoxicity.

The first group 60 participants will be randomized 1:1 to either Tempol 600 mg daily or placebo. Assuming that treatment is well tolerated but ≥20% of the participants in the active arm have grade 3 or 4 mucositis, a second group of 60 participants may be enrolled, and randomized 1:1 to receive either Tempol 1000 mg daily or placebo.

Throughout the treatment period, participants will take study medication twice daily on both chemo/radiation days and cancer treatment free days. On radiation/chemo days, participants will be instructed to take study medication 10 minutes before each proton therapy or radiation treatment (400 or 600 mg) and again in the evening (200 or 400 mg) no less than 6 hours following the first dose. Participants will begin to take study medication two (2) days before their scheduled cancer treatment. When proton therapy or radiation is not administered, participants will take the medication twice daily, 400 mg or 600 mg in the morning and 200 mg or 400 mg in the evening. On the day of radiation therapy, study medication will be administered within 10 minutes prior to each course of radiotherapy. Participants will be instructed to hold the solution in their mouth swishing for approximately 30 seconds and then swallow.


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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 : May 2020
Estimated Study Completion Date : May 2020

Arm Intervention/treatment
Active Comparator: Active 600 mg Tempol Solution
Patients will take 600 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. Ototoxicity [ Time Frame: 10 weeks ]
    Maintenance of participant performance levels as measured on the Distortion-product otoacoustic emissions (DPOAE) scale prior to and following cancer treatment.

  5. 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.




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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 definitive 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 Eastern Cooperative Oncology Group (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 hearing loss;
  15. Participants with known intolerance to platin drugs;
  16. History of insulin-dependent Diabetes Mellitus; and
  17. 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: Louis Habash 9498367936 lh@matrixbiomed.com

Locations
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United States, California
UCSD Recruiting
La Jolla, California, United States, 92093
Contact: Gerald Henderson    858-822-5223    gehenderson@ucsd.edu   
Principal Investigator: James Urbanic, MD         
United States, Kansas
The University of Kansas Cancer Center Not yet recruiting
Westwood, Kansas, United States, 66205
Contact: Christopher Baierl, BSc    913-588-3058    cbaierl@kumc.edu   
Principal Investigator: Christopher Lominska, MD         
United States, Maryland
University Maryland School of Medicine Recruiting
Baltimore, Maryland, United States, 21201
Contact: Kaysee Baker    410-328-2635    Kaysee.Baker@umm.edu   
Principal Investigator: Robert Malyapa, MD         
United States, Missouri
Washington University Not yet recruiting
Saint Louis, Missouri, United States, 63110
Contact: Josh Smith, CCRP    314-362-9427    smith473@wustl.edu   
Principal Investigator: Douglas Adkins, MD         
Sponsors and Collaborators
Matrix Biomed, Inc.
University of Maryland, College Park
Investigators
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Principal Investigator: Robert Malyapa, MD University of Maryland, College Park

Publications:

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Responsible Party: Matrix Biomed, Inc.
ClinicalTrials.gov Identifier: NCT03480971     History of Changes
Other Study ID Numbers: MBI-04-04
First Posted: March 29, 2018    Key Record Dates
Last Update Posted: June 10, 2019
Last Verified: May 2019
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
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Mouth Diseases
Stomatognathic Diseases
Pharmaceutical Solutions
Cisplatin
Tempol
TEMPO
Antineoplastic Agents
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Protein Synthesis Inhibitors
Enzyme Inhibitors
Radiation-Protective Agents
Neuroprotective Agents