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

NCT03515538 | Completed Phase 2 Results FDA Drug

• 1 other identifier: PR-001
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 12

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.

Conditions

Oral Mucositis

Keywords

head and neck cancer; squamous; neck cancer; oral cancer; mucositis; sores; mouth

Outcome Measures

Primary Outcomes (1)

• Duration of Severe Oral Mucositis (SOM)

  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.

  From start of treatment through 28 days post treatment for up to 11 weeks from Start of Treatment

Secondary Outcomes (3)

• Time to Onset of Severe Oral Mucositis

  Time from Day 1 to Oral Mucositis Onset (up to 8 weeks)

• Incidence of Severe Oral Mucositis

  Baseline through end of treatment (up to 11 weeks). Data collected every week.

• Opioid Use

  Baseline through end of radiation treatment (through 8 weeks). Data collected every week.

Study Arms (4)

RRx-001 Pre-Treatment plus SOC

EXPERIMENTAL

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

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

RRx-001 Pre-Treatment, 2 Concurrent Doses plus SOC

EXPERIMENTAL

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

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

RRx-001 Pre-Treatment, 6 Concurrent Doses plus SOC

EXPERIMENTAL

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

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

Standard of Care

ACTIVE COMPARATOR

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).

Drug: Cisplatin for injection; Radiation: Radiation Therapy

Interventions

RRx-001 DRUG

RRx-001 for injection

RRx-001 Pre-Treatment plus SOC; RRx-001 Pre-Treatment, 2 Concurrent Doses plus SOC; RRx-001 Pre-Treatment, 6 Concurrent Doses plus SOC

Cisplatin for injection DRUG

Patients will receive 3 doses of cisplatin at 100 mg/m2 in accordance with applicable guidelines such as NCCN; however, these guidelines are not intended to supersede or replace institutional guidelines with respect to appropriate and necessary care for individual patients

RRx-001 Pre-Treatment plus SOC; RRx-001 Pre-Treatment, 2 Concurrent Doses plus SOC; RRx-001 Pre-Treatment, 6 Concurrent Doses plus SOC; Standard of Care

Radiation Therapy RADIATION

Intensity Modulated Radiation Therapy (IMRT) in accordance with the American College of Radiology (ACR) and American Society for Radiation Oncology (ASTRO) Practice Guideline for IMRT) is mandatory for this study

RRx-001 Pre-Treatment plus SOC; RRx-001 Pre-Treatment, 2 Concurrent Doses plus SOC; RRx-001 Pre-Treatment, 6 Concurrent Doses plus SOC; Standard of Care

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• EpicentRx, Inc.: lead
• Prothex, Inc.: collaborator

Study Sites (12)

John Wayne Cancer Institute @ Providence St. John's Health Center

Santa Monica, California, 90401, United States

Location

Centura Health Research Center

Denver, Colorado, 80210, United States

Location

George Washington University

Washington D.C., District of Columbia, 20037, United States

Location

Florida Hospital

Orlando, Florida, 32804, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

East Carolina University

Greenville, North Carolina, 27834, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45267, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Ballad Health

Johnson City, Tennessee, 37604, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

UT Southwestern

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Stomatitis; Head and Neck Neoplasms; Mouth Neoplasms; Mucositis

Interventions

RRx-001; Cisplatin; Injections; Radiotherapy

Condition Hierarchy (Ancestors)

Mouth Diseases; Stomatognathic Diseases; Neoplasms by Site; Neoplasms; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Drug Administration Routes; Drug Therapy; Therapeutics

Results Point of Contact

• Title: Bryan Oronsky
• Organization: EpicentRx, Inc

mstirn@epicentrx.com

858-229-1062

Study Officials

• Bryan Oronsky, MD, PhD

  EpicentRx, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2018
• First Posted: May 3, 2018
• Study Start: July 12, 2018
• Primary Completion: October 22, 2019
• Study Completion: October 8, 2020
• Last Updated: November 4, 2024
• Results First Posted: November 4, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (12)