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

NCT05966194 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: K-01
• Study Type: interventional
• Target: 216
• Locations: 1 country
• Sites: 14

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.

Conditions

Oral Mucositis

Keywords

Head and Neck Cancer; Neck cancer; Oral cancer; Mucositis; Squamous cell carcinoma (SCC); HPV; Oropharynx; Oral cavity; IMRT

Outcome Measures

Primary Outcomes (1)

• Incidence of Severe Oral Mucositis (SOM) through Intensity-modulated radiation therapy (IMRT)

  The incidence of SOM defined as the proportion of patients with any WHO Grade \>= 3 (severe to life threatening) oral mucositis during the observation period from the start of CRT through IMRT

  Estimated up to 18 Months

Secondary Outcomes (13)

• Duration of Severe Oral Mucositis (SOM) through Intensity-modulated radiation therapy (IMRT)

  Estimated up to 18 Months

• Duration of Severe Oral Mucositis (SOM) through 60 Gy

  Estimated up to 18 Months

• Time to onset of Sever Oral Mucositis (ttSOM)

  Estimated up to 18 Months

• Incidence and severity of dysphagia

  Estimated up to 18 Months

• Cumulative radiation dose to onset of SOM

  Estimated up to 18 Months

Study Arms (3)

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

EXPERIMENTAL

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

Drug: RRx-001; Radiation: Intensity Modulated Radiation Therapy (IMRT); Drug: Cisplatin for injection 100 mg/m2

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

EXPERIMENTAL

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.

Drug: RRx-001; Radiation: Intensity Modulated Radiation Therapy (IMRT); Drug: Cisplatin for injection 100 mg/m2

Placebo Pre-Treatment + Chemoradiation Therapy (CRT)

PLACEBO COMPARATOR

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.

Radiation: Intensity Modulated Radiation Therapy (IMRT); Drug: Cisplatin for injection 100 mg/m2

Interventions

RRx-001 DRUG

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

RRx-001 Pre-Treatment (4mg RRx-001) + Chemoradiation Therapy (CRT); RRx-001 Pre-Treatment (8mg RRx-001) + Chemoradiation Therapy (CRT)

Intensity Modulated Radiation Therapy (IMRT) RADIATION

Intensity Modulated Radiation Therapy of up to 72 Gy

Placebo Pre-Treatment + Chemoradiation Therapy (CRT); RRx-001 Pre-Treatment (4mg RRx-001) + Chemoradiation Therapy (CRT); RRx-001 Pre-Treatment (8mg RRx-001) + Chemoradiation Therapy (CRT)

Cisplatin for injection 100 mg/m2 DRUG

Cisplatin for injection 100 mg/m2

Placebo Pre-Treatment + Chemoradiation Therapy (CRT); RRx-001 Pre-Treatment (4mg RRx-001) + Chemoradiation Therapy (CRT); RRx-001 Pre-Treatment (8mg RRx-001) + Chemoradiation Therapy (CRT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• ECOG performance status ≤ 2.
• 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
• 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
• 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.
• Age 18 years or older
• 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.
• Ability and willingness to understand and sign a written informed consent document.
• 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
• 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.

You may not qualify if:

• Prior radiotherapy to the head and neck region.
• Prior induction chemotherapy.
• Tumors of the lips, salivary gland, nasopharynx, hypopharynx, or larynx.
• Patients with simultaneous primaries
• Stage IV, M1 (distant metastasis)
• Prior or current use of approved or investigational anticancer agent other than those provided in this study.
• Grade 3 or 4 dysphagia or odynophagia (National Cancer Institute Common Toxicity Criteria, version 5.0) or inability to eat a normal (solid) diet
• 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.
• 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.
• Active infectious disease excluding oral candidiasis.
• Presence of oral mucositis (WHO Score ≥ Grade 1) or other oral mucosal ulceration at baseline.
• Untreated active oral or dental infection
• Known history of human immunodeficiency virus or active hepatitis B or C.
• 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)
• 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.

Sponsors & Collaborators

• EpicentRx, Inc.: lead

Study Sites (14)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

RECRUITING

The University of Arizona Cancer Center

Tucson, Arizona, 85719, United States

RECRUITING

Miami Cancer Institute

Miami, Florida, 33176, United States

RECRUITING

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611, United States

RECRUITING

Parkview Cancer Institute

Fort Wayne, Indiana, 46845, United States

RECRUITING

Willis Knighton Cancer Center

Shreveport, Louisiana, 71103, United States

RECRUITING

Sandra and Malcolm Berman Cancer Institute

Baltimore, Maryland, 21204, United States

RECRUITING

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

Renown Regional Medical Center

Reno, Nevada, 89502, United States

RECRUITING

East Carolina University School of Medicine

Greenville, North Carolina, 27834, United States

RECRUITING

The Ohio State University James Cancer Hospital & Solove Research Institute

Columbus, Ohio, 43210, United States

RECRUITING

Ballad Health

Johnson City, Tennessee, 37604, United States

RECRUITING

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

University of Virginia

Charlottesville, Virginia, 22908, United States

RECRUITING

Related Publications (1)

• 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.

  PMID: 36646388 BACKGROUND

MeSH Terms

Conditions

Stomatitis; Head and Neck Neoplasms; Mouth Neoplasms; Mucositis; Carcinoma, Squamous Cell

Interventions

RRx-001; Radiotherapy, Intensity-Modulated; Cisplatin; Injections

Condition Hierarchy (Ancestors)

Mouth Diseases; Stomatognathic Diseases; Neoplasms by Site; Neoplasms; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Drug Administration Routes; Drug Therapy

Study Officials

• Meaghan Stirn

  EpicentRx, Inc.

  STUDY DIRECTOR

Central Study Contacts

Scott Caroen

CONTACT

8589476635; scaroen@epicentrx.com

Jeannie Williams

CONTACT

8589476635; jwilliams@epicentrx.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2023
• First Posted: July 28, 2023
• Study Start: April 2, 2024
• Primary Completion: July 1, 2025
• Study Completion: October 1, 2025
• Last Updated: November 15, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (14)