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

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ClinicalTrials.gov Identifier: NCT03515538
Recruitment Status : Completed
First Posted : May 3, 2018
Last Update Posted : January 11, 2021
Sponsor:
Collaborator:
Prothex Pharma, Inc.
Information provided by (Responsible Party):
EpicentRx, Inc.

Tracking Information
First Submitted Date  ICMJE April 18, 2018
First Posted Date  ICMJE May 3, 2018
Last Update Posted Date January 11, 2021
Actual Study Start Date  ICMJE July 12, 2018
Actual Primary Completion Date October 22, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 3, 2018)
Duration of Severe Oral Mucositis (SOM) [ Time Frame: up to one year ]
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 5=oral alimentation impossible. Sever 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 Sever Oral Mucositis duration numbers are indicative of worst outcomes. The total Sever 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.
Original Primary Outcome Measures  ICMJE
 (submitted: May 2, 2018)
Duration of Severe Oral Mucositis (SOM) [ Time Frame: up to one year ]
Duration in days of severe oral mucositis (SOM). Defined as oral mucositis grade 3 or 4 (WHO Mucositis Grading Scale).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 3, 2018)
  • Time to onset of Sever Oral Mucositis [ Time Frame: up to one year ]
    Time to onset of Sever Oral Mucositis defined as time (in days) from randomization to the first observed Sever Oral Mucositis. Longer Sever Oral Mucositis onset times are indicative of a better outcome. The time to onset of Sever 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 Sever Oral Mucositis [ Time Frame: up to one year ]
    Incidence of Sever Oral Mucositis defined as the proportion of patients experiencing Sever Oral Mucositis during the randomized treatment period. Sever Oral Mucositis incidence range is 0 to 100%, and higher percentages are indicative of worse outcomes.
  • Duration of ulcerative Oral Mucositis [ Time Frame: up to one year ]
    Duration (in days) of ulcerative oral mucositis defined as the proportion of patients experiencing oral mucositis during the randomized treatment period. Defined as oral mucositis grade 0 or 1 on the WHO Mucositis Grading Scale (described above). Longer duration of ulcerative oral mucositis is indicative of a worse outcome. The total ulcerative 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.
  • Incidence of ulcerative Oral Mucositis [ Time Frame: up to one year ]
    Incidence of ulcerative oral mucositis defined as the proportion of patients experiencing ulcerative oral mucositis during the randomized treatment period. Ulcerative oral mucositis is defined as oral mucositis grade 0 or 1 on the WHO Mucositis Grading Scale (described above) and ranges from 0 to 100% with higher percentages being indicative of worse outcomes.
  • Patient-reported pain [ Time Frame: up to one year ]
    Patient-reported mouth and throat soreness score obtained from Question #2 from the Oral Mucositis Daily Questionnaire (OMDQ) filled out by the patient. OMDQ Question #2 asked "During the last 24 hours, how much mouth and throat soreness did you have?". OMDQ Question # 2 uses the following five-point categorical scale to quantity mouth and throat soreness: 0=no soreness, 1=a little soreness, 2=moderate soreness, 3=quite a lot of soreness and 4=extreme soreness. Higher mouth and throat soreness values are indicative of worse outcomes. The range of the month and throat values is 0, 1, 2, 3, 4.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 2, 2018)
  • Time to onset of SOM [ Time Frame: up to one year ]
    Time to onset of SOM defined as time (in days) from randomization to the first observed SOM.
  • Incidence of SOM [ Time Frame: up to one year ]
    Duration (in days) of ulcerative oral mucositis defined as the proportion of patients experiencing oral mucositis during the randomized treatment period
  • Duration and incidence of ulcerative OM [ Time Frame: up to one year ]
    Incidence of ulcerative oral mucositis defined as the proportion of patients experiencing ulcerative oral mucositis during the randomized treatment period.
  • Patient-reported pain [ Time Frame: up to one year ]
    Patient-report mouth and throat soreness graded on a discrete scale from 0 to 4 (0 = no soreness, . . . , 4 = extreme soreness).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of RRx-001 in the Attenuation of Oral Mucositis in Patients Receiving Chemoradiation for the Treatment of Oral Cancers
Official Title  ICMJE A Phase 2a Randomized, Parallel Group, Open Label, Multicenter Study to Assess the Safety and Efficacy of RRx-001 in the Attenuation of Oral Mucositis in Patients Receiving Chemoradiation for the Treatment of Locally Advanced Squamous Cell Carcinoma of the Oral Cavity or Oropharynx
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Condition  ICMJE Oral Mucositis
Intervention  ICMJE
  • Drug: RRx-001
    RRx-001 for injection
  • Drug: Cisplatin for injection
    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
  • Radiation: Radiation Therapy
    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
Study Arms  ICMJE
  • Experimental: RRx-001 Pre-Treatment plus SOC
    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
    Interventions:
    • Drug: RRx-001
    • Drug: Cisplatin for injection
    • Radiation: Radiation Therapy
  • Experimental: RRx-001 Pre-Treatment, 2 Concurrent Doses plus SOC
    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
    Interventions:
    • Drug: RRx-001
    • Drug: Cisplatin for injection
    • Radiation: Radiation Therapy
  • Experimental: RRx-001 Pre-Treatment, 6 Concurrent Doses plus SOC
    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
    Interventions:
    • Drug: RRx-001
    • Drug: Cisplatin for injection
    • Radiation: Radiation Therapy
  • Active Comparator: Standard of Care
    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).
    Interventions:
    • Drug: Cisplatin for injection
    • Radiation: Radiation Therapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 9, 2019)
48
Original Estimated Enrollment  ICMJE
 (submitted: May 2, 2018)
40
Actual Study Completion Date  ICMJE October 8, 2020
Actual Primary Completion Date October 22, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. 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
  2. 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.
  3. ECOG performance status ≤ 2.
  4. 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

  5. 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

  6. 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.
  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 to understand and sign a written informed consent document.
  10. 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
  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 radiation to the head and neck
  2. Tumor of the lips, nasopharynx, hypopharynx, larynx, or salivary glands
  3. Patients with simultaneous primaries or bilateral tumors
  4. Metastatic disease (M1) Stage IV
  5. 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
  6. Presence of oral mucositis (WHO Score ≥ Grade 1) or other oral mucosal ulceration at study entry
  7. Grade 3 or 4 dysphagia or odynophagia (National Cancer Institute Common Toxicity Criteria, version 5.0) or inability to eat a normal diet
  8. Requirement at baseline for parenteral or gastrointestinal tube-delivered nutrition for any reason
  9. 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)
  10. 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).
  11. Pregnant or nursing
  12. Untreated active oral or dental infection, including severe tooth decay (caries)
  13. Known allergies or intolerance to cisplatin and similar platinum-containing compounds
  14. Evidence of immediate life-threatening disease or a life expectancy of less than 3 months
  15. Receipt of unapproved or off-label medication within 30 days prior to start of study treatment
  16. Sjogren syndrome
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03515538
Other Study ID Numbers  ICMJE PR-001
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party EpicentRx, Inc.
Study Sponsor  ICMJE EpicentRx, Inc.
Collaborators  ICMJE Prothex Pharma, Inc.
Investigators  ICMJE
Study Director: Bryan Oronsky, MD, PhD EpicentRx, Inc.
PRS Account EpicentRx, Inc.
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP