Clinical trial NCT05966194: RRx-001 for Reducing Oral Mucositis in Patients Receiving Chemotherapy and Radiation for Head and Neck Cancer
Official title: A Randomized Placebo-Controlled Trial of Two Schedules of RRx-001 for the Attenuation of Severe Oral Mucositis in Patients Receiving Concomitant Chemoradiation for the Treatment of Locally Advanced Squamous Cell Carcinoma of the Oral Cavity or Oropharynx
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Oral Mucositis
Keywords: Head and Neck Cancer
Neck cancer
Oral cancer
Mucositis
Squamous cell carcinoma (SCC)
HPV
Oropharynx
Oral cavity
IMRT
Lead sponsor: EpicentRx, Inc.
Sponsor class: INDUSTRY
First posted: 2023-07-28
Enrollment: 216
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: The standard treatment for head and neck cancer currently includes a chemotherapy drug called cisplatin that is given by intravenous (IV) infusion and radiation, which is delivered from a machine that precisely targets the tumor. One common and unfortunate side effect of treatment with cisplatin and radiation is oral mucositis, which refers to irritation of the lining of the mouth. Oral mucositis is a serious problem 1) because the open mouth sores from oral mucositis may lead to severe pain, nutritional problems and dehydration from an inability to eat and drink, an increased risk of infection from bacteria and fungus and delay or discontinuation of treatment and 2) because there is only one approved therapy to treat or prevent it.

Eligibility criteria: Inclusion Criteria:

1. Pathologically confirmed diagnosis of squamous cell carcinoma (SCC) of the oral cavity or oropharynx Note: Patients with primary cancers that are presumed to be of oropharyngeal origin may be included if they meet radiation field dosing criteria as specified in Inclusion Criterion #2 below. Unknown primaries which are HPV+ are acceptable. HPV determination must be made for all patients.
2. Radiation Treatment planned to receive standard IMRT with daily fractions of 2.0 to 2.2 Gy for a total cumulative dose of 60-72 Gy in conjunction with definitive or adjuvant chemotherapy. Planned radiation treatment fields must include at least two oral sites (soft palate, floor of mouth, buccal mucosa, tongue) that are each planned to receive a total of \> 55 Gy. Patients who have had prior surgery are eligible, provided they have fully recovered from surgery, and patients who may have surgery in the future are eligible.
3. ECOG performance status ≤ 2.
4. Participants must have adequate organ and marrow function as defined below:

   • Absolute neutrophil count (ANC) ≥ 1,500 / mm3 2. Platelets ≥ 75,000 / mm3 3. Hemoglobin ≥ 9.0 g/dL
5. Adequate renal and liver function as indicated by:

   • Serum creatinine acceptable for treatment with cisplatin per institutional guidelines) 2. Total bilirubin ≤ 1.5 x upper-normal limit (ULN) 3. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN 4. Alkaline phosphatase ≤ 2.5 x ULN
6. Human papilloma virus (HPV) status in tumor must be documented using tumor immunohistochemistry for HPV-p16 or other accepted test (such as such as in situ hybridization) for patients with cancers of the oropharynx (Rooper et al, 2016, Martens 2017). HPV status at baseline optional for oral cavity tumors.
7. Age 18 years or older
8. Patient must consent to the access, review, and analysis of previous medical and cancer history, including imaging data, by the sponsor or a third party nominated by the sponsor.
9. Ability and willingness to understand and sign a written informed consent document.
10. Women of childbearing potential and men with partners of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy.

    Note: A woman of child-bearing potential is any female (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
    * Has not undergone a hysterectomy or bilateral oophorectomy; or
    * Has not been postmenopausal for at least 12 consecutive months
11. Adequate visual access to permit examination of the following oral cavity sites: lips, buccal mucosa, floor of mouth, ventral and lateral tongue, and soft palate.

Exclusion Criteria:

1. Prior radiotherapy to the head and neck region.
2. Prior induction chemotherapy.
3. Tumors of the lips, salivary gland, nasopharynx, hypopharynx, or larynx.
4. Patients with simultaneous primaries
5. Stage IV, M1 (distant metastasis)
6. Prior or current use of approved or investigational anticancer agent other than those provided in this study.
7. Grade 3 or 4 dysphagia or odynophagia (National Cancer Institute Common Toxicity Criteria, version 5.0) or inability to eat a normal (solid) diet
8. Requirement at baseline for parenteral or gastrointestinal tube-delivered nutrition for any reason or prophylactic insertion of gastrostomy tube with dependency on tube feeding at baseline.
9. Malignant tumors other than squamous cell carcinoma of the head and neck within last 5 years, unless treated definitively and with low risk of recurrence in the judgment of the treating investigator.
10. Active infectious disease excluding oral candidiasis.
11. Presence of oral mucositis (WHO Score ≥ Grade 1) or other oral mucosal ulceration at baseline.
12. Untreated active oral or dental infection
13. Known history of human immunodeficiency virus or active hepatitis B or C.
14. Any significant medical diseases or conditions, as assessed by the investigators and sponsor that would substantially increase the medical risks of participating in this study (e.g, immunosuppression, uncontrolled diabetes, NYHA II-IV congestive heart failure, myocardial infarction within 6 months of study, severe chronic pulmonary disease or active uncontrolled infection, uncontrolled or clinically relevant pulmonary edema)
15. Use of the following within 48 hours of enrollment and duration of Oral Mucositis follow up: vitamin B12 (cobalamin) or synthetic vitamin B12, cyanocobalamin, or the vitamin B12 precursor, cobinamide, or any supplement or multivitamin with vitamin B12 or vitamin E in it since both vitamin B12 and vitamin E interact negatively with RRx-001.
16. Use of prebiotics and probiotics
17. Pregnant or nursing.
18. Known allergies or intolerance to cisplatin or other platinum-containing compounds.
19. Sjogren syndrome

Primary outcomes:
measure: Incidence of Severe Oral Mucositis (SOM) through Intensity-modulated radiation therapy (IMRT)
timeFrame: Estimated up to 18 Months
Secondary outcomes:
measure: Duration of Severe Oral Mucositis (SOM) through Intensity-modulated radiation therapy (IMRT)
timeFrame: Estimated up to 18 Months
measure: Duration of Severe Oral Mucositis (SOM) through 60 Gy
timeFrame: Estimated up to 18 Months
measure: Time to onset of Sever Oral Mucositis (ttSOM)
timeFrame: Estimated up to 18 Months
measure: Incidence and severity of dysphagia
timeFrame: Estimated up to 18 Months
measure: Cumulative radiation dose to onset of SOM
timeFrame: Estimated up to 18 Months
measure: Incidence of grade 4 oral mucositis
timeFrame: Estimated up to 18 Months
measure: Narcotic use through resolution of SOM
timeFrame: Estimated up to 18 Months
measure: Incidence of Severe Oral Mucositis through 60 Gy of the Radiation Treatment Plan
timeFrame: Estimated up to 18 Months
measure: Progression free survival (PFS)
timeFrame: Estimated up to 24 Months
measure: Degree of Xerostomia
timeFrame: Estimated up to 24 Months
measure: Xerostomia duration
timeFrame: Estimated up to 24 Months
measure: Time to onset of dysphagia
timeFrame: Estimated up to 24 Months
measure: Duration of dysphagia
timeFrame: Estimated up to 24 Months
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Tucson
country: United States
facility: The University of Arizona Cancer Center
state: Arizona
city: Miami
country: United States
facility: Miami Cancer Institute
state: Florida
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine
state: Illinois
city: Fort Wayne
country: United States
facility: Parkview Cancer Institute
state: Indiana
city: Shreveport
country: United States
facility: Willis Knighton Cancer Center
state: Louisiana
city: Baltimore
country: United States
facility: Sandra and Malcolm Berman Cancer Institute
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Reno
country: United States
facility: Renown Regional Medical Center
state: Nevada
city: Greenville
country: United States
facility: East Carolina University School of Medicine
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University James Cancer Hospital & Solove Research Institute
state: Ohio
city: Johnson City
country: United States
facility: Ballad Health
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
Study officials:
affiliation: EpicentRx, Inc.
name: Meaghan Stirn
role: STUDY_DIRECTOR
References:
citation: Bonomi M, Blakaj DM, Kabarriti R, Colvett K, Takiar V, Biagioli M, Bar-Ad V, Goyal S, Muzyka B, Niermann K, Abrouk N, Oronsky B, Reid T, Caroen S, Sonis S, Sher DJ. 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. Int J Radiat Oncol Biol Phys. 2023 Jul 1;116(3):551-559. doi: 10.1016/j.ijrobp.2022.12.031. Epub 2023 Jan 14.