Neoplasms

All Conditions

Mouth and Tooth Diseases

Digestive System Diseases

Carcinoma

Carcinoma, Squamous Cell

Head and Neck Neoplasms

Stomatitis

Mucositis

Oral Ulcer

Gastroenteritis

Gastrointestinal Diseases

Mouth Diseases

Stomatognathic Diseases

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Cisplatin

Manganese

Superoxide Dismutase

Avasopasem manganese

Trace Elements

Antioxidants

Protective Agents

GC4419 90mg

Placebo

Gene Kennedy, MD

The purpose of the phase 3, clinical study is to determine if GC4419 (avasopasem manganese) administered prior to intensity-modulated radiation therapy (IMRT) reduces the severity of radiation induced oral mucositis in patients who have been diagnosed with locally advanced, non-metastatic squamous cell carcinoma of the head and neck.

ROMAN: Phase 3 Trial Investigating the Effects of GC4419 on Radiation Induced Oral Mucositis in Head/Neck Cancer Patients

ROMAN: Reduction in Oral Mucositis With Avasopasem Manganese (GC4419) - Phase 3 Trial in Patients Receiving Chemoradiotherapy for Locally-Advanced, Non-Metastatic Head and Neck Cancer

Cumulative incidence of severe oral mucositis is defined as the proportion of subjects with any occurrence of WHO Grade 3 to 4 OM, during the Study Treatment Period. Incidence of severe OM is defined as any occurrence of WHO Grade 3 or 4 OM through the last IMRT fraction after the start of IMRT. Incidence was imputed using multiple imputation for subjects with incomplete follow-up for severe OM through 60 Gy who did not have an occurrence of severe OM before the last IMRT fraction.

Galera Therapeutics, Inc.

GC4419 (Avasopasem Manganese) 90 mg

GC4419 (avasopasem manganese): 60 minute IV infusion

GC4419 (Avasopasem Manganese)

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Canada

United States

Region of Enrollment

Intent-to-Treat (ITT) population includes all randomized subjects who received at least one dose of GC4419/Placebo, with the exception of the 28 subjects whose treatment course was discontinued during the Sponsor's voluntary suspension of dosing.

Megan Holm

GC4419 (Avasopasem Manganese) 90mg

The Intent to treat population consisted of all randomized subjects who received at least 1 dose of avasopasem manganese or placebo (with the exception of subjects whose treatment course was discontinued due to the sponsor's voluntary suspension of dosing)

Cumulative Incidence of Severe Oral Mucositis

Overall Study

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Anti-Inflammatory Agents

Pharmaceutical Solutions

Antiemetics

Neuroprotective Agents

Gastrointestinal Agents

Hydrocortisone

Hydrocortisone 17-butyrate 21-propionate

Hydrocortisone acetate

Hydrocortisone hemisuccinate

Hormones

Everolimus

Prednisolone

Methylprednisolone

Methylprednisolone Acetate

Methylprednisolone Hemisuccinate

Prednisolone acetate

Prednisolone hemisuccinate

Prednisolone phosphate

Glucocorticoids

Hormone Antagonists

Antineoplastic Agents, Hormonal

Miracle Mouthwash plus Hydrocortisone, swish and expectorate 10cc (10 mLs) 4 times per day, every day for 12 weeks.

Prednisolone oral solution 15 mg/5 ml; swish and expectorate 10cc (10 mL) 4 times per day, every day for 12 weeks.

Miracle Mouthwash Plus Hydrocortisone (16 oz recipe/480 ml)

Miracle Mouthwash Plus Hydrocortisone

Joyce A. O'Shaughnessy, MD

This is a randomized Phase 2 study to evaluate two different steroid-based mouth rinses (Miracle Mouth Wash plus hydrocortisone versus prednisolone oral rinse) for the prevention or treatment of everolimus-associated stomatitis (mouth sores) in postmenopausal patients undergoing treatment with an aromatase inhibitor plus everolimus. An exploratory analysis will also evaluate patient response to next anti-cancer therapy of physician's choice following discontinuation of therapy with an aromatase inhibitor plus everolimus.

Stomatitis, or inflammation of the mucous membranes lining the mouth and throat, is a common side affect associated with chemotherapy and radiation therapy. In addition, stomatitis has been reported in approximately 44% - 64% of patients treated with everolimus (Afinitor PI). However, mTOR (mammalian target of rapamycin) inhibitor-induced stomatitis (mIAS) is a different clinical entity, manifesting more frequently as discrete aphthous-like lesions rather than diffuse inflammation. Oral lesions are typically well demarcated, single or multiple ovoid-shaped ulcerations, with a grayish-white pseudomembrane.

In the BOLERO-2 trial, 56% of patients with MBC (metastatic breast cancer) treated with exemestane plus everolimus developed stomatitis, with 37% developing grade 2/3 stomatitis. These rates are consistent with the rates reported with everolimus therapy in patients with other types of cancers (Afinitor PI). Although this adverse event is reversible, approximately one-fourth of the patients treated with everolimus in the BOLERO-2 trial required dose interruptions or dose reductions, and this may impact the benefit from therapy. Despite the frequency of stomatitis associated with mTOR inhibitor therapy, strategies to prevent and/or ameliorate this painful side effect are not well defined or documented. Expert guidelines on the management of mIAS have been developed, but these guidelines are based on retrospective observational and/or anecdotal evidence, and prospective data on the efficacy of mIAS prevention and management strategies are needed.

There is some evidence to suggest steroid therapy may be helpful in the management of mIAS. Steroid-containing ointments or mouth rises have also been shown to alleviate symptoms in patients with non-chemotherapy associated apthous oral ulcers. Reports on the effectiveness of non-steroid mouthwash formulations have been mixed, but agents that induce a topical anesthetic effect, may help to reduce discomfort and pain.

Thus, the present study has been designed to investigate the effectiveness of two oral rinses (miracle mouth wash \[MMW\] plus hydrocortisone, vs prednisolone) to prevent or reduce the severity of stomatitis in patients with MBC undergoing treatment with an aromatase inhibitor plus everolimus (AIE).

In addition, because very little is known about the impact of everolimus therapy on response to later lines of treatment for MBC, and preclinical data suggest mTOR inhibition may resensitize cells to endocrine therapy, this study will also assess tumor response to next anti-cancer therapy of physician's choice, including duration of response and sites of progression.

All patients will receive everolimus 10 mg PO QD (by mouth, every day) plus standard dose AI (physician choice of Letrozole, Exemestane, or Anastrozole).

Patients will be randomized 1:1 to 12 weeks of treatment with either:

* Arm 1: MMW plus hydrocortisone
* Arm 2: Prednisolone oral solution (15mg/5ml)

Treatment with the oral rinse will start on Day 1 of everolimus therapy, and will be self-administered. Patients will be instructed to swish and expectorate (cough or spit out) 10ml of the assigned mouth rinse 4 times per day. Patients may also gargle 4 times per day with the assigned rinse for any symptoms of pharyngitis. Patients will also be instructed to fill out the Oral Stomatitis Daily Questionnaire (OSDQ) at home every day.

The incidence of stomatitis, as well as other adverse events, dose reductions/interruptions, and everolimus discontinuation due to toxicity, will be monitored for the first 12 weeks of treatment. After the end of the initial 12 week randomized portion of the study, patients will continue to be followed every 2 months (for up to 1 year following discontinuation of everolimus for progression or intolerable toxicity or progression on subsequent anti-cancer therapy, whichever occurs first) to determine when AIE treatment is discontinued and reason for discontinuation (toxicity, progression), sites of disease progression, response to next anti-cancer therapy of physician's choice (by physician assessment) and duration of response, and sites of disease progression to next anti-cancer therapy following progression on AIE.

Miracle Mouthwash Plus Hydrocortisone vs Prednisolone Mouth Rinse for Mouth Sores Caused by Everolimus

Evaluation of Miracle Mouthwash (MMW) Plus Hydrocortisone and Prednisolone Mouth Rinse as Prophylaxis for Everolimus-Associated Stomatitis

An exploratory objective is to assess patient response to the next anti-cancer therapy of physician's choice following progression on AIE, including duration of response and sites of progression.

The primary objective of the study is to determine the incidence of Grade ≥ 2 stomatitis in patients undergoing treatment with an aromatase inhibitor plus everolimus (AIE) when treated with either Miracle Mouthwash (MMW) plus hydrocortisone or with a prednisolone mouth rinse during the first 12 weeks of treatment.

Determination of the incidence of adverse events (all grades)

Determination of the percentage of patients requiring dose interruptions and/or dose reductions of everolimus, as well as the percentage of patients discontinuing therapy with everolimus due to toxicity.

Evaluation of the impact of MMW plus hydrocortisone or a prednisolone mouth rinse on the duration and severity of stomatitis, as assessed by the Oral Stomatitis Daily Questionnaire (OSDQ).

Novartis Pharmaceuticals

US Oncology Research

Ear, Nose, and Throat Diseases

Oropharyngeal Neoplasms

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Pharyngeal Diseases

Otorhinolaryngologic Diseases

Antihypertensive Agents

Analgesics

Clonidine

Sympatholytics

Adrenergic Agents

Adrenergic alpha-Agonists

Adrenergic Agonists

Neurotransmitter Agents

Placebo Mucoadhesive Buccal Tablet given daily during chemoradiotherapy

Clonidine HCl MBT given daily during chemoradiotherapy

Clonidine HCl Mucoadhesive Buccal Tablet

Placebo Mucoadhesive Buccal Tablet

Holli Carlson

This study is being performed to evaluate the effectiveness of a new drug, clonidine HCl MBT, to prevent the onset of severe oral mucositis (SOM) in patients with oropharyngeal cancer (OPC) who are being treated with chemoradiotherapy. OPC occurs on the back of the tongue or throat and is often treated by the use of chemoradiotherapy, where radiation is localized to these areas. Radiation to the OPC affected tissues causes the release of small proteins called cytokines that cause damage to the area surrounding the tumor including the oral cavity. This damage is characterized by the formation of mucositis which includes redness, pain and ulcers in the mouth and back of the throat. In addition, as more chemoradiation is administered to treat OPC, the inability to eat a solid diet (a Grade 3 mucositis) or to consume anything at all by mouth (a Grade 4 mucositis) occurs in many patients. Collectively, Grade 3 and Grade 4 mucositis is referred to as SOM. It is a frequent, debilitating side effect of chemoradiation in OPC that may cause patients to stop or interrupt their treatment, develop other side effects like the inability to swallow, or require the increased use of pain medications. OPC survivors who have successful treatment of their tumors often develop permanent swallowing, speaking and range of motion issues that may be linked back to the inability to eat and/or drink caused by SOM during their chemoradiotherapy treatment. Clonidine may inhibit the production of cytokines that cause SOM and clonidine HCl mucoadhesive buccal tablet (MBT) has been designed to deliver sustained high levels of clonidine in the oral cavity, potentially decreasing cytokine production and leading to a decrease in the incidence of SOM. Clonidine HCl MBT is a once per day treatment provided as a tablet that a patient may self-administer to the gums, where it sticks tightly to release clonidine over many hours. The primary objective of this Phase 2b/3 study is to evaluate whether clonidine HCl MBT is more effective than placebo MBT in decreasing the incidence of SOM.

This is a sequential design Phase 2b/3 multicenter, randomized (1:1), double-blind, placebo-controlled, parallel group study to compare the efficacy and safety of clonidine HCl MBT to placebo MBT in the prevention of severe oral mucositis (SOM) in patients with oropharyngeal cancer (OPC) undergoing chemoradiotherapy (CRT). Best supportive care (BSC) will be allowed as per individual institutional practice with some exceptions as described in the inclusion and exclusion criteria. Eligible patients will be randomized to receive either clonidine MBT or placebo. Patients will be centrally randomized in a 1:1 ratio. The randomization will be stratified by p16 status (positive or negative). Randomized patients will be required to self-apply the study drug to the gum once a day in addition to BSC. The first application of MBT study drug will be performed on Day 1 of the CRT regimen. Each site will require the patient to follow the same local practice for BSC per Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) guidelines with some exceptions as described in the inclusion and exclusion criteria. Daily, self-administered MBT study drug will be continued once daily for the entire duration of CRT treatment; defined as from Day 1 of CRT until the last day of CRT (anticipated to be approximately 4-8 weeks depending on the patient's prescribed CRT plan). Patients will be recruited sequentially into either the Phase 2b or the Phase 3 part of the study. An interim analysis will be conducted when Phase 2b patients have either completed their CRT or discontinued from the study. The Data Monitoring Committee (DMC) will review the Phase 2b efficacy and safety data at the interim analysis and will make a recommendation on proceeding with the Phase 3 part of the study.

Clonidine HCl MBT vs. Placebo to Prevent Chemoradiotherapy-Induced Severe Oral Mucositis in Oropharyngeal Cancer.

A Phase 2b/3, Multicenter, Randomized, Double-blind, Placebo-controlled Study Comparing the Efficacy and Safety of Clonidine Mucoadhesive Buccal Tablet to Placebo to Prevent Chemoradiotherapy-induced Severe Oral Mucositis in Patients With Oropharyngeal Cancer

The occurrence of SOM (Yes/No), defined as any reporting of World Health Organization (WHO) Grade 3-4 OM, from the first day to the last day of CRT. The WHO mucositis grading scale will be used to assess the occurrence of SOM in this trial. The WHO grading scale grades OM from 0 to 4 according to severity of clinical observation and functional limitation, with Grade 4 = oral alimentation impossible, Grade 3 = Oral ulcers, liquid diet only, Grade 2 = Oral erythema, ulcers, solid diet tolerated, Grade 1 = Oral soreness, erythema, and Grade 0 = normal, no mucositis (no signs, no symptoms).

Evaluate the safety and tolerability of administering HCl MBT to OPC patients receiving CRT by assessing the number and severity of treatment-emergent adverse events (TEAE) and specifically those TEAEs of special interest. Adverse events are graded and tabulated using NCI CTCAE v5.0.

Monopar Therapeutics

Symptoms and General Pathology

Respiratory Tract (Lung and Bronchial) Diseases

Pain

Xerostomia

Laryngeal Diseases

Mitogens

Participants received a single intravenous dose of palifermin at 180 μg/kg three days before the start of radiotherapy, and then 7 once weekly palifermin doses at the same dose level during a 7-week radiotherapy/chemotherapy course.

Participants received a single IV dose of placebo three days before the start of radiotherapy, and then 7 once weekly placebo doses during a 7-week radiotherapy/chemotherapy course.

palifermin

Commercially available cisplatin was administered as an intravenous infusion at a dose of 100 mg/m\^2 on Days 1, 22, and 43.

cisplatin chemotherapy

Radiotherapy was delivered in 200 cGy daily fractions, 5 days a week.

Radiotherapy

The purpose of this research study is to test the safety and effectiveness of palifermin to determine if weekly doses can be safely administered to reduce the incidence (occurrence of), duration (length of time) and severity (amount of pain) of oral mucositis (painful sores in the mouth). Mucositis is a common side effect for patients receiving chemotherapy (cancer-killing drug) and radiotherapy (cancer-killing x-rays) for the treatment of head and neck cancer (HNC).

This study consisted of 2 phases. The acute oral mucositis (OM) evaluation phase includes the time from randomization to the time of severe OM (WHO Grade 3 or 4) resolution (up to Week 12 or up to Week 15 for participants whose severe OM is not resolved at Week 12). In the acute OM evaluation phase, participants were randomized to receive either a single IV dose of palifermin or placebo at 180 μg/kg, 3 days before the start of radiotherapy, plus 7 once-weekly palifermin or placebo doses at the same dose level during a 7-week radio/chemotherapy course. In the long-term follow up phase, participants are followed until death, withdrawal of consent, or loss to follow-up. The long-term follow up phase is still ongoing.

Palifermin for the Reduction of Oral Mucositis in Patients With Locally Advanced Head and Neck Cancer

Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Weekly Doses of Palifermin (rHuKGF) for the Reduction of Oral Mucositis in Subjects With Advanced Head and Neck Cancer Receiving Radiotherapy With Concurrent Chemotherapy (RT/CT)

Participants underwent evaluations of oral mucosal (OM) surfaces (mucositis assessments) 2 times weekly throughout radio/chemotherapy, and 2 times weekly thereafter until severe OM returned to grade ≤ 2 or until Week 15. During each evaluation, the following anatomical areas were assessed: upper lip; lower lip; right cheek; left cheek; right ventral \& lateral tongue; left ventral \& lateral tongue; floor of the mouth; hard palate; soft palate. A trained evaluator documented the findings using the World Health Organization (WHO) oral toxicity scale according to the following: Grade 0 = None; Grade 1 = Soreness, erythema; Grade 2 = Erythema, ulcers, ability to eat solids; Grade 3 = Ulcers, requires liquid diet; Grade 4 = Alimentation not possible.

The duration of severe oral mucositis (OM) was calculated as the number of days from the onset of severe OM (first time a WHO grade 3 or 4 was observed) to the day when severe OM was resolved (first time WHO grade 2 or less was observed after last WHO grade 3 or 4). Durations of 0 days were assigned to those participants who did not experience any WHO grade 3 or 4 during the study.

Time to onset of severe (WHO Grade 3 or 4) oral mucositis (OM) was analyzed using the Kaplan-Meier procedure.

Participants without an assessed event by the end of the acute OM evaluation phase were censored at the date of last assessment for severe OM.

The number of participants with grade 2 or higher xerostomia (dryness of the oral mucosa) at the Month 4 visit, graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v3.0 Dry Mouth/Xerostomia scale.

The average patient-reported mouth and throat soreness (MTS) score as reported on question 3 of the Oral Mucositis Weekly Questionnaire for Head and Neck Cancer \[OMWQ-HN\]): "How much mouth and throat soreness did you experience in the past 24 hours?" Participants answered on a scale from 0 (no soreness) to 4 (extreme soreness).

For each participant, an average patient-reported mouth and throat soreness score was calculated by dividing the sum of the MTS scores at each assessment by the total number of assessments.

The total dose of opioid analgesics (mg of intravenous \[IV\] morphine equivalents) used by all participants.

Participants with at least one reported administration of opioid analgesic (parenteral, peroral or transdermal) were considered to have received opioid analgesics. The total dose of opioid analgesics is the sum of all opioid analgesic administrations that have been converted to morphine equivalents.

Cisplatin was administered on Days 1, 22, and 43. An unplanned break in cisplatin refers to a delay of ≥ 5 days from the scheduled Day 22 or Day 43 cisplatin administration or a discontinuation of cisplatin for any reason.

Participants with a duration of 5 days or more without an administration of radiotherapy or who discontinue radiotherapy prior to completion of planned radiotherapy were considered to have an unplanned break in radiotherapy.

Amgen

Swedish Orphan Biovitrum

The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.

Participants received a single intravenous (IV) dose of placebo three days before the start of radiotherapy, and then 7 once weekly placebo doses during a 7-week radiotherapy/chemotherapy course.

Palifermin

Age, Continuous

Caucasian

Black

Hispanic

American Indian/ Alaska Native

Race/Ethnicity, Customized

Data available for 91 and 94 participants in each treatment group respectively.

Weight

Stage III

Stage IV A

Stage IV B

American Joint Committee on Cancer staging system.

Disease Stage

Oral Cavity

Oropharynx

Nasopharynx

Larynx

Hypopharynx

Tumor Site

Hans Olivecrona, MD PhD

Sample size calculations were based on the number of participants needed to detect, with 90% power and 5% type 1 error rate, at least a 25% difference in the incidence of severe OM between the treatment groups. A 25% absolute reduction in the incidence of severe OM from the placebo group was considered by investigators as clinically meaningful in this clinical setting.

Unknown

The Full Analysis Set included all randomized participants.

Number of Participants With Severe (Grade 3 or 4) Oral Mucositis

To protect the overall type 1 error, the Hochberg procedure was used to adjust for multiple statistical testing of the secondary efficacy endpoints.

Duration of Severe (WHO Grade 3 or 4) Oral Mucositis

Time to Onset of Severe (WHO Grade 3 or 4) Oral Mucositis

Number of Participants With Xerostomia at Month 4 (Grade 2 or Higher)

The Patient Reported Outcome-evaluable analysis set included all randomized patients with a valid Baseline assessment for MTS question 3 of the OMWQ-HN and either:

* At least 1 completed assessment each week for MTS up to withdrawal/Week 8, whichever came first, or
* 70% or greater overall compliance for MTS until withdrawal/Week 8.

Patient-Reported Mouth and Throat Soreness Score

Total Dose of Opioid Analgesics Used for Mucositis Within 15 Weeks

Number of Participants With Unplanned Breaks in Cisplatin Chemotherapy Treatment

Number of Participants With Unplanned Breaks in Radiotherapy

Participants received a single intravenous (IV) dose of placebo three days before the start of radiotherapy, and then 7 once weekly placebo doses during a 7-week radiotherapy/chemotherapy course. Chemotherapy consisted of 100 mg/m\^2 cisplatin administered by IV infusion on Days 1, 22, and 43.

Participants received a single intravenous dose of palifermin at 180 μg/kg three days before the start of radiotherapy, and then 7 once weekly palifermin doses at the same dose level during a 7-week radiotherapy/chemotherapy course. Chemotherapy consisted of 100 mg/m\^2 cisplatin administered by IV infusion on Days 1, 22, and 43.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
ROMAN: Phase 3 Trial Investigating the Effects of GC4419 on Radiation Induced Oral Mucositis in Head/Neck Cancer Patients	NCT03689712	Oral Mucositis	GC4419 90mg Placebo	18 Years -	Galera Therapeutics, Inc.
Miracle Mouthwash Plus Hydrocortisone vs Prednisolone Mouth Rinse for Mouth Sores Caused by Everolimus	NCT02229136	Stomatitis Oral Mucositis Neoplasm of the... Malignant Tumor...	Miracle Mouthwa... Prednisolone	18 Years -	US Oncology Research
Miracle Mouthwash Plus Hydrocortisone vs Prednisolone Mouth Rinse for Mouth Sores Caused by Everolimus	NCT02229136	Stomatitis Oral Mucositis Neoplasm of the... Malignant Tumor...	Miracle Mouthwa... Prednisolone	18 Years -	US Oncology Research
Clonidine HCl MBT vs. Placebo to Prevent Chemoradiotherapy-Induced Severe Oral Mucositis in Oropharyngeal Cancer.	NCT04648020	Chemoradiothera...	Clonidine HCl M... Placebo Mucoadh...	18 Years -	Monopar Therapeutics
Palifermin for the Reduction of Oral Mucositis in Patients With Locally Advanced Head and Neck Cancer	NCT00101582	Mucositis Solid Tumors Stomatitis Head and Neck C... Squamous Cell C...	Placebo palifermin cisplatin chemo... Radiotherapy	18 Years -	Swedish Orphan Biovitrum

Spots Global Cancer Trial Database for mouth sores

Every month we try and update this database with for mouth sores cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for mouth sores

Every month we try and update this database with for mouth sores cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for mouth sores cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.