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
|Condition or disease||Intervention/treatment||Phase|
|Mucositis Nephrotoxicity Ototoxicity||Drug: Tempol Drug: Placebo Solution||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||120 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|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|
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)
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.
- 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.
- 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.
- Nephrotoxicity [ Time Frame: 10 weeks ]Reduction in Serum Creatinine levels in active arm versus placebo arm.
- Nephrotoxicity [ Time Frame: 10 weeks ]Reduction in Blood Urea Nitrogen levels in active arm versus placebo arm.
- 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.
- 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.
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
|Contact: Louis Habashfirstname.lastname@example.org|
|United States, California|
|La Jolla, California, United States, 92093|
|Contact: Gerald Henderson 858-822-5223 email@example.com|
|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 firstname.lastname@example.org|
|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 email@example.com|
|Principal Investigator: Douglas Adkins, MD|
|Principal Investigator:||Robert Malyapa, MD||University of Maryland, College Park|