Safety and Efficacy of RRx-001 in the Attenuation of Oral Mucositis in Patients Receiving Chemoradiation for the Treatment of Oral Cancers

Phase 2

Completed

Conditions: Oral Mucositis

Interventions: Drug: RRx-001
Drug: Cisplatin for injection
Radiation: Radiation Therapy

Registration Number: NCT03515538

Lead Sponsor: EpicentRx, Inc.

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 duration or length 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 in arms 1, 2 and 3 will also receive RRx-001 on different schedules.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 53

Inclusion Criteria

Pathologically confirmed diagnosis of squamous cell carcinoma (SCC) of the oral cavity and oropharynx Note: Patients with unknown primary tumors whose treatment plan matches the requirements specified in Inclusion Criterion #3 below are eligible for the trial
Treatment planned to include standard cisplatin monotherapy administered either every three weeks (100 mg/m2 for 3 doses) with concomitant radiation delivered as a continuous course of IMRT with single daily fractions of 2.0 to 2.2 Gy with a cumulative radiation dose between 60 Gy and 72 Gy. Planned radiation treatment fields must include at least two oral sites (buccal mucosa, floor of mouth, tongue, soft palate) 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:

A. Absolute neutrophil count (ANC) >1,500 / mm3 B. Platelets > 100,000 / mm3 C. Hemoglobin ≥ 9.0 g/dL
Adequate renal and liver function as indicated by:

A. Serum creatinine acceptable for treatment with cisplatin per institutional guidelines) B. Total bilirubin ≤ 1.5 x upper-normal limit (ULN) C. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN D. Alkaline phosphatase ≤ 2.5 x ULN
Human papilloma virus (HPV) status in tumor has been documented using tumor immunohistochemistry for HPV-p16 or other accepted test for patients with cancers of the oropharynx, base of tongue, or unknown primary.
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 to understand and sign a written informed consent document.
Women of child-bearing potential and men with partners of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) 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.

Exclusion Criteria

Prior radiation to the head and neck
Tumor of the lips, nasopharynx, hypopharynx, larynx, or salivary glands
Patients with simultaneous primaries or bilateral tumors
Metastatic disease (M1) Stage IV
Malignant tumors other than HNC within the last 5 years, unless treated definitively and with low risk of recurrence in the judgment of the treating investigator
Presence of oral mucositis (WHO Score ≥ Grade 1) or other oral mucosal ulceration at study entry
Grade 3 or 4 dysphagia or odynophagia (National Cancer Institute Common Toxicity Criteria, version 5.0) or inability to eat a normal diet
Requirement at baseline for parenteral or gastrointestinal tube-delivered nutrition for any reason
Known history of HIV or active hepatitis B/C (patients who have been vaccinated for hepatitis B and do not have a history of infection are eligible)
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 (i.e., 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).
Pregnant or nursing
Untreated active oral or dental infection, including severe tooth decay (caries)
Known allergies or intolerance to cisplatin and similar platinum-containing compounds
Evidence of immediate life-threatening disease or a life expectancy of less than 3 months
Receipt of unapproved or off-label medication within 30 days prior to start of study treatment
Sjogren syndrome

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
RRx-001 Pre-Treatment, 2 Concurrent Doses plus SOC	Cisplatin for injection	Two infusions of RRx-001 will be given each week during the two weeks prior to the start of RT/cisplatin SOC. In addition, one dose of RRx-001 will be given on the last radiation day in each of weeks 2 and 5 during RT/cisplatin administration
Standard of Care	Cisplatin for injection	No doses of RRx-001 will be administered. Patients assigned to this arm will receive only standard of care in the form of a 7-week course of fractionated radiation therapy concurrent with a high-dose cisplatin regimen (100 mg/m2 dose in each of RT weeks 1, 4, and 7).
RRx-001 Pre-Treatment plus SOC	Cisplatin for injection	Two infusions of RRx-001 will be given each week during the two weeks prior to the start of RT/cisplatin SOC (four doses total). No additional RRx-001 will be given during the course of RT/cisplatin
Standard of Care	Radiation Therapy	No doses of RRx-001 will be administered. Patients assigned to this arm will receive only standard of care in the form of a 7-week course of fractionated radiation therapy concurrent with a high-dose cisplatin regimen (100 mg/m2 dose in each of RT weeks 1, 4, and 7).
RRx-001 Pre-Treatment plus SOC	Radiation Therapy	Two infusions of RRx-001 will be given each week during the two weeks prior to the start of RT/cisplatin SOC (four doses total). No additional RRx-001 will be given during the course of RT/cisplatin
RRx-001 Pre-Treatment, 6 Concurrent Doses plus SOC	Cisplatin for injection	Two infusions of RRx-001 will be given each week during the two weeks prior to the start of RT/cisplatin SOC. In addition, one dose of RRx-001 will be given on the last radiation day of each of the first 6 weeks during RT/cisplatin administration
RRx-001 Pre-Treatment, 6 Concurrent Doses plus SOC	Radiation Therapy	Two infusions of RRx-001 will be given each week during the two weeks prior to the start of RT/cisplatin SOC. In addition, one dose of RRx-001 will be given on the last radiation day of each of the first 6 weeks during RT/cisplatin administration
RRx-001 Pre-Treatment, 2 Concurrent Doses plus SOC	Radiation Therapy	Two infusions of RRx-001 will be given each week during the two weeks prior to the start of RT/cisplatin SOC. In addition, one dose of RRx-001 will be given on the last radiation day in each of weeks 2 and 5 during RT/cisplatin administration
RRx-001 Pre-Treatment plus SOC	RRx-001	Two infusions of RRx-001 will be given each week during the two weeks prior to the start of RT/cisplatin SOC (four doses total). No additional RRx-001 will be given during the course of RT/cisplatin
RRx-001 Pre-Treatment, 2 Concurrent Doses plus SOC	RRx-001	Two infusions of RRx-001 will be given each week during the two weeks prior to the start of RT/cisplatin SOC. In addition, one dose of RRx-001 will be given on the last radiation day in each of weeks 2 and 5 during RT/cisplatin administration
RRx-001 Pre-Treatment, 6 Concurrent Doses plus SOC	RRx-001	Two infusions of RRx-001 will be given each week during the two weeks prior to the start of RT/cisplatin SOC. In addition, one dose of RRx-001 will be given on the last radiation day of each of the first 6 weeks during RT/cisplatin administration

Primary Outcome Measures

Name	Time	Method
Duration of Severe Oral Mucositis (SOM)	From start of treatment through 28 days post treatment for up to 11 weeks from Start of Treatment	Duration in days of severe oral mucositis (SOM). Defined as oral mucositis grade 3 or 4 on the WHO Mucositis Grading Scale which comprises 5 grades: 0 = none, 1= oral soreness, erythema, 2 = oral erythema, ulcers, solid diet tolerated, 3 = oral ulcers, liquid diet only, and 4 = oral alimentation impossible. Severe Oral Mucositis duration is obtained by totaling the number of days a given patient experiences oral mucositis grade 3 or 4 during the randomized treatment period. Higher Severe Oral Mucositis duration numbers are indicative of worst outcomes. The total Severe Oral Mucositis duration for a given patient will range between 0 days and the maximum number of days the patient participated in the randomized treatment period.

Secondary Outcome Measures

Name	Time	Method
Time to Onset of Severe Oral Mucositis	Time from Day 1 to Oral Mucositis Onset (up to 8 weeks)	Time to onset of Severe Oral Mucositis defined as time (in days) from randomization to the first observed Severe Oral Mucositis. Longer Severe Oral Mucositis onset times are indicative of a better outcome. The time to onset of Severe Oral Mucositis for a given patient will range between 0 days and the maximum number of days the patient participated in the randomized treatment period.
Incidence of Severe Oral Mucositis	Baseline through end of treatment (up to 11 weeks). Data collected every week.	Incidence of Severe Oral Mucositis defined as the number of patients who experienced a Severe Oral Mucositis grade 4 during the randomized treatment period.
Opioid Use	Baseline through end of radiation treatment (through 8 weeks). Data collected every week.	Opioid use from the time to onset (TTO) and duration of opioid use among patients who were not taking opioids at radiation start or who required a second opioid during active treatment.

Trial Locations

Locations (12): UT Southwestern
🇺🇸
Dallas, Texas, United States
John Wayne Cancer Institute @ Providence St. John's Health Center
🇺🇸
Santa Monica, California, United States
Ohio State University
🇺🇸
Columbus, Ohio, United States
George Washington University
🇺🇸
Washington, District of Columbia, United States
East Carolina University
🇺🇸
Greenville, North Carolina, United States
Ballad Health
🇺🇸
Johnson City, Tennessee, United States
Centura Health Research Center
🇺🇸
Denver, Colorado, United States
Florida Hospital
🇺🇸
Orlando, Florida, United States
University of Cincinnati Medical Center
🇺🇸
Cincinnati, Ohio, United States
Vanderbilt-Ingram Cancer Center
🇺🇸
Nashville, Tennessee, United States
Montefiore Medical Center
🇺🇸
Bronx, New York, United States
Thomas Jefferson University
🇺🇸
Philadelphia, Pennsylvania, United States