RRx-001 for Reducing Oral Mucositis in Patients Receiving Chemotherapy and Radiation for Head and Neck Cancer

NCT ID: NCT05966194

Last Updated: 2024-11-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

216 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-04-02

Study Completion Date

2025-10-01

Brief Summary

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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

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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.

Conditions

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Oral Mucositis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Outcome Assessors

Study Groups

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RRx-001 Pre-Treatment (8mg RRx-001) + Chemoradiation Therapy (CRT)

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 Type EXPERIMENTAL

RRx-001

Intervention Type DRUG

RRx-001 for injection (4 mg or 8 mg)

Intensity Modulated Radiation Therapy (IMRT)

Intervention Type RADIATION

Intensity Modulated Radiation Therapy of up to 72 Gy

Cisplatin for injection 100 mg/m2

Intervention Type DRUG

Cisplatin for injection 100 mg/m2

RRx-001 Pre-Treatment (4mg RRx-001) + Chemoradiation Therapy (CRT)

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 Type EXPERIMENTAL

RRx-001

Intervention Type DRUG

RRx-001 for injection (4 mg or 8 mg)

Intensity Modulated Radiation Therapy (IMRT)

Intervention Type RADIATION

Intensity Modulated Radiation Therapy of up to 72 Gy

Cisplatin for injection 100 mg/m2

Intervention Type DRUG

Cisplatin for injection 100 mg/m2

Placebo Pre-Treatment + Chemoradiation Therapy (CRT)

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.

Group Type PLACEBO_COMPARATOR

Intensity Modulated Radiation Therapy (IMRT)

Intervention Type RADIATION

Intensity Modulated Radiation Therapy of up to 72 Gy

Cisplatin for injection 100 mg/m2

Intervention Type DRUG

Cisplatin for injection 100 mg/m2

Interventions

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RRx-001

RRx-001 for injection (4 mg or 8 mg)

Intervention Type DRUG

Intensity Modulated Radiation Therapy (IMRT)

Intensity Modulated Radiation Therapy of up to 72 Gy

Intervention Type RADIATION

Cisplatin for injection 100 mg/m2

Cisplatin for injection 100 mg/m2

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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EpicentRx, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Meaghan Stirn

Role: STUDY_DIRECTOR

EpicentRx, Inc.

Locations

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Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

Site Status RECRUITING

The University of Arizona Cancer Center

Tucson, Arizona, United States

Site Status RECRUITING

Miami Cancer Institute

Miami, Florida, United States

Site Status RECRUITING

Northwestern University Feinberg School of Medicine

Chicago, Illinois, United States

Site Status RECRUITING

Parkview Cancer Institute

Fort Wayne, Indiana, United States

Site Status RECRUITING

Willis Knighton Cancer Center

Shreveport, Louisiana, United States

Site Status RECRUITING

Sandra and Malcolm Berman Cancer Institute

Baltimore, Maryland, United States

Site Status RECRUITING

University of Michigan

Ann Arbor, Michigan, United States

Site Status RECRUITING

Renown Regional Medical Center

Reno, Nevada, United States

Site Status RECRUITING

East Carolina University School of Medicine

Greenville, North Carolina, United States

Site Status RECRUITING

The Ohio State University James Cancer Hospital & Solove Research Institute

Columbus, Ohio, United States

Site Status RECRUITING

Ballad Health

Johnson City, Tennessee, United States

Site Status RECRUITING

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status RECRUITING

University of Virginia

Charlottesville, Virginia, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Scott Caroen

Role: CONTACT

8589476635

Jeannie Williams

Role: CONTACT

8589476635

Facility Contacts

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Erin Nicoson

Role: primary

480-256-5484

Alana Sudkamp

Role: primary

520-694-4377

Amy Starosciak

Role: primary

786-596-2000

Role: primary

312-695-0990

Brian Chang, MD

Role: primary

833-724-8326

Briana Barrow

Role: primary

318-212-8671

Laura Morse Cucci

Role: primary

Brandy Slusser

Role: primary

Role: primary

775-982-5050

Kristin Wooten

Role: primary

252-744-3617

Harley Hamilton

Role: primary

614-685-6493

Charles Mays, III, PhD

Role: primary

423-431-5654

Sarah Neufeld

Role: primary

214-648-1836

Rachael Zhang

Role: primary

434-982-1901

References

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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.

Reference Type BACKGROUND
PMID: 36646388 (View on PubMed)

Other Identifiers

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K-01

Identifier Type: -

Identifier Source: org_study_id

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