RRx-001 for Mouth Sores in Head and Neck Cancer

(KEVLARx Trial)

Recruiting at13 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: EpicentRx, Inc.

Must not be taking: Vitamin B12, Vitamin E

Disqualifiers: Prior radiotherapy, Stage IV M1, others

Prior Safety Data

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine if RRx-001, which is added on to the cisplatin and radiation treatment, reduces the incidence of severe oral mucositis in patients with head and neck cancers. All patients in this study will receive 7 weeks of standard of care radiation therapy given with the chemotherapy agent, cisplatin. Patients will receive RRx-001 or placebo before start of standard of care treatment.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications, but you cannot use vitamin B12, vitamin E, prebiotics, or probiotics during the study.

What data supports the effectiveness of the drug RRx-001 for mouth sores in head and neck cancer?

The PREVLAR trial suggests that RRx-001 may be safe and feasible for reducing oral mucositis (painful mouth sores) in patients undergoing chemoradiotherapy for head and neck cancer, although further studies are needed to confirm its effectiveness. ^{1 2 3 4 5}

Is RRx-001 safe for humans?

In a phase 2a trial, RRx-001 was tested for safety in patients with head and neck cancer receiving chemoradiotherapy, and the study was designed to assess its safety and feasibility. This suggests that RRx-001 has been evaluated for safety in humans, although specific safety outcomes from the trial are not detailed in the abstract. ^{1 3 4 6 7}

How does the drug RRx-001 differ from other treatments for mouth sores in head and neck cancer?

RRx-001 is unique because it targets nuclear retinoid receptors, which are involved in cell growth and differentiation, potentially reversing premalignant lesions and inhibiting cancer development. This mechanism is different from other treatments like cetuximab or immunotherapies that target specific proteins on cancer cells. ^{8 9 10 11 12}

Research Team

Meaghan Stirn

Principal Investigator

EpicentRx, Inc.

Eligibility Criteria

This trial is for adults with squamous cell carcinoma of the oral cavity or oropharynx, who can undergo standard radiation and cisplatin chemotherapy. They must have an ECOG performance status ≤ 2, acceptable organ function tests, documented HPV status if applicable, and agree to use contraception. Prior surgery patients are eligible if recovered.

Inclusion Criteria

I agree to use effective birth control during the study.

Patient must consent to the access, review, and analysis of previous medical and cancer history by the sponsor or a third party.

I am 18 years old or older.

Exclusion Criteria

I do not have any active infections, except for oral thrush.

I cannot eat normally due to severe swallowing pain or difficulty.

I have a history of HIV or active hepatitis B or C.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Treatment

Participants receive RRx-001 or placebo twice weekly for 2 weeks prior to the start of chemoradiation therapy

2 weeks

4 visits (in-person)

Chemoradiation Therapy

Participants receive 7 weeks of standard of care radiation therapy with the chemotherapy agent, cisplatin

7 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Estimated up to 24 months

Treatment Details

Interventions

• RRx-001 (Other)

Trial Overview The study is testing whether RRx-001 reduces severe mouth sores when added to standard chemotherapy (cisplatin) and radiation therapy in head and neck cancer patients. Everyone gets the usual treatment; some will also get RRx-001 while others receive a placebo before starting treatment.

Participant Groups

Group I: RRx-001 Pre-Treatment (8mg RRx-001) + Chemoradiation Therapy (CRT) Experimental Treatment 3 Interventions

Pretreatment consists of 8 mg RRx-001 given twice weekly during the 2 weeks prior to the start of CRT (4 doses total) followed by the CRT treatment period

Group II: RRx-001 Pre-Treatment (4mg RRx-001) + Chemoradiation Therapy (CRT) Experimental Treatment 3 Interventions

Pretreatment consists of 4 mg RRx-001 given twice weekly during the 2 weeks prior to the start of CRT (4 doses total) followed by the CRT treatment period.

Group III: Placebo Pre-Treatment + Chemoradiation Therapy (CRT) Placebo Group 2 Interventions

No doses of RRx-001 will be administered. Patients assigned to this arm will receive placebo twice weekly during the 2 weeks prior to the start of CRT followed by the CRT treatment period.

Who Is Running the Clinical Trial?

EpicentRx, Inc.

Lead Sponsor

Trials

16

Recruited

1,000+

Findings from Research

RRx-001 is a safe and feasible treatment for oral mucositis (OM) in patients undergoing chemoradiotherapy for head and neck cancers, with no severe adverse events reported during the study involving 53 patients.

Patients receiving RRx-001 experienced a significantly shorter duration of severe oral mucositis, with the lowest median duration of 8.5 days compared to 24 days in the control group, suggesting potential efficacy that warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PREVLAR: Phase 2a Randomized Trial to Assess the Safety and Efficacy of RRx-001 in the Attenuation of Oral Mucositis in Patients Receiving Head and Neck Chemoradiotherapy. Bonomi, M., Blakaj, DM., Kabarriti, R., et al.[2023]

In a review of 13 randomized controlled trials involving 650 patients with head and neck cancer, antioxidants like vitamin E and zinc significantly reduced the severity of oral mucositis compared to placebo, with vitamin E reducing the risk of severe mucositis by 60% and zinc by 95%.

Despite these promising results, the overall quality of evidence is low due to the limited number of studies and potential biases, indicating a need for larger, more rigorous trials to confirm the effectiveness of these antioxidants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of oral and topical antioxidants in the prevention and management of oral mucositis in head and neck cancer patients: a systematic review and meta-analyses. Raza, A., Karimyan, N., Watters, A., et al.[2022]

In a study of 90 patients with locally advanced nasopharyngeal carcinoma, the oral mucosal protectant RADoralex® significantly reduced the incidence and severity of radiation-induced oral mucositis compared to a sodium bicarbonate solution.

Patients using RADoralex® experienced a shorter time to healing and less weight loss during treatment, indicating its efficacy in improving oral health and quality of life during radiochemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the efficacy of the anti-ulcer oral mucosal protective agent RADoralex® in the prevention and treatment of radiation-induced oral mucosal reactions induced during treatment of nasopharyngeal carcinoma. Yin, J., Xie, J., Lin, J., et al.[2022]

In a phase II clinical trial involving 108 participants, Dentoxol mouthrinse used 5 times a day during radiation therapy for head and neck cancer significantly reduced the number of assessments showing severe oral mucositis compared to a control mouthrinse.

Dentoxol was found to be safe, with no serious adverse events reported, and it delayed the onset of severe oral mucositis, suggesting its potential as an effective treatment option for patients undergoing radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of Dentoxol® in the prevention of radiation-induced oral mucositis in head and neck cancer patients (ESDOM): a randomized, multicenter, double-blind, placebo-controlled, phase II trial. Lalla, RV., Solé, S., Becerra, S., et al.[2021]

A systematic review and meta-analysis of 25 studies, involving various mouthwash formulations, found that mouthwashes with anti-inflammatory properties are the most effective in reducing oral mucositis in head and neck cancer patients undergoing radiation therapy.

The study highlights the importance of selecting mouthwashes with specific ingredients to alleviate the painful side effects of radiation therapy, improving patient comfort during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effectiveness of mouthwashes in alleviating radiation-induced oral mucositis in head and neck cancer patients: a systematic review. Konishi, M., Verdonschot, RG., Shimabukuro, K., et al.[2020]

In a randomized clinical trial involving 36 head-and-neck cancer patients, a non-alcohol based mouth-rinse containing chlorhexidine and cetylpyridinium chloride showed a smaller increase in mucositis severity compared to a placebo, suggesting potential benefits in managing oral complications during radiation therapy.

Despite the lack of statistically significant differences between the treatment and placebo groups, the results indicate that the mouth-rinse may offer some clinical improvements in oral health for patients undergoing radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mucositis in irradiated cancer patients: effects of an antiseptic mouthrinse. Lanzós, I., Herrera, D., Santos, S., et al.[2019]

In a study of 67 head and neck cancer patients, the use of Amifostine alongside radiotherapy significantly reduced symptoms of dry mouth and oral discomfort, as evidenced by a decrease in questionnaire scores from 6.49 to 3.73.

Amifostine also lowered the incidence of severe mucositis from 75% to 36% and acute xerostomia from 82% to 39%, with a higher rate of salivary gland function returning to normal (36.3% in the Amifostine group vs. 9.1% in the control group).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Amifostine to prevent radiotherapy-induced acute and late toxicity in head and neck cancer patients who had normal or mild impaired salivary gland function. Veerasarn, V., Phromratanapongse, P., Suntornpong, N., et al.[2013]

Patients with recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) have a poor prognosis, but new treatments targeting specific pathways are emerging.

Cetuximab, pembrolizumab, and nivolumab are FDA-approved therapies that target the epidermal growth factor receptor and PD-1, respectively, showing promise in improving treatment outcomes for R/M HNSCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted Therapy in Head and Neck Cancer: An Update on Current Clinical Developments in Epidermal Growth Factor Receptor-Targeted Therapy and Immunotherapies. Moreira, J., Tobias, A., O'Brien, MP., et al.[2022]

Retinoids can reverse premalignant lesions and inhibit second primary cancers in patients with upper aerodigestive tract cancers, likely by restoring normal cell growth and differentiation.

The study found that decreased expression of the RAR-beta receptor is significantly associated with the development of head and neck squamous cell carcinoma (HNSCC), suggesting its potential role as a biomarker for cancer progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential expression of nuclear retinoid receptors in normal, premalignant, and malignant head and neck tissues. Xu, XC., Ro, JY., Lee, JS., et al.[2022]

Immune checkpoint inhibitors represent a major advancement in treating recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), improving patient outcomes significantly.

Oral metronomic therapy has become an important treatment option, especially for low to middle-income countries, while H-RAS inhibition is emerging as a promising area for future research in HNSCC therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in pharmacotherapy for head and neck cancer. Kumar, S., Noronha, V., Patil, V., et al.[2021]

The EXTREME regimen, which combines cetuximab with platinum and 5-fluorouracil, remains the standard treatment for previously untreated patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC).

Nivolumab, an anti-PD-1 monoclonal antibody, is now considered the standard of care for patients with R/M HNSCC who have progressed after platinum-based therapy, showing a survival benefit over other treatments in the CheckMate 141 trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing treatments for recurrent or metastatic head and neck squamous cell carcinoma. Specenier, P., Vermorken, JB.[2019]

Targeting the CXCR1/2 receptors with new pharmacological inhibitors, particularly compound C29, shows promise in reducing tumor growth and inflammation in clear cell renal cell carcinoma (RCC) and head and neck squamous cell carcinomas (HNSCC), especially in cases resistant to standard treatments like sunitinib and cisplatin.

High levels of ELR+CXCL cytokines were found to correlate with shorter survival in patients, indicating that these cytokines and their receptors are critical targets for developing effective therapies against these aggressive cancer types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New CXCR1/CXCR2 inhibitors represent an effective treatment for kidney or head and neck cancers sensitive or refractory to reference treatments. Dufies, M., Grytsai, O., Ronco, C., et al.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

PREVLAR: Phase 2a Randomized Trial to Assess the Safety and Efficacy of RRx-001 in the Attenuation of Oral Mucositis in Patients Receiving Head and Neck Chemoradiotherapy. [2023]

2. Germany pubmed.ncbi.nlm.nih.gov

Efficacy of oral and topical antioxidants in the prevention and management of oral mucositis in head and neck cancer patients: a systematic review and meta-analyses. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Evaluation of the efficacy of the anti-ulcer oral mucosal protective agent RADoralex® in the prevention and treatment of radiation-induced oral mucosal reactions induced during treatment of nasopharyngeal carcinoma. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and safety of Dentoxol® in the prevention of radiation-induced oral mucositis in head and neck cancer patients (ESDOM): a randomized, multicenter, double-blind, placebo-controlled, phase II trial. [2021]

5. Japan pubmed.ncbi.nlm.nih.gov

The effectiveness of mouthwashes in alleviating radiation-induced oral mucositis in head and neck cancer patients: a systematic review. [2020]

6. Spain pubmed.ncbi.nlm.nih.gov

Mucositis in irradiated cancer patients: effects of an antiseptic mouthrinse. [2019]

7. Thailand pubmed.ncbi.nlm.nih.gov

Effect of Amifostine to prevent radiotherapy-induced acute and late toxicity in head and neck cancer patients who had normal or mild impaired salivary gland function. [2013]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Targeted Therapy in Head and Neck Cancer: An Update on Current Clinical Developments in Epidermal Growth Factor Receptor-Targeted Therapy and Immunotherapies. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Differential expression of nuclear retinoid receptors in normal, premalignant, and malignant head and neck tissues. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Advances in pharmacotherapy for head and neck cancer. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Optimizing treatments for recurrent or metastatic head and neck squamous cell carcinoma. [2019]

12. Australia pubmed.ncbi.nlm.nih.gov

New CXCR1/CXCR2 inhibitors represent an effective treatment for kidney or head and neck cancers sensitive or refractory to reference treatments. [2020]