A Study of the Effects of GC4419 on Radiation Induced Oral Mucositis in Patients With Head/Neck Cancer
Condition: Radiation Induced Oral Mucositis
MeSH terms: Mucositis; Stomatitis
Intervention: Low Dose GC4419: 30mg/day; High Dose GC4419: 90mg/day; Placebo; Intensity-Modulated Radiation Therapy; Cisplatin
Intervention description: Low Dose GC4419 will be administered by 60 minute IV infusion, within 1 hour prior to daily IMRT fractions, until IMRT is complete (generally M-F for approximately 7 weeks).; High Dose GC4419 will be administered by 60 minute IV infusion, within 1 hour prior to daily IMRT fractions, until IMRT is complete (generally M-F for approximately 7 weeks).; Placebo will be administered by 60 minute IV infusion, within 1 hour prior to daily IMRT fractions, until IMRT is complete (generally M-F for approximately 7 weeks).; Daily fractions of IMRT (2.0-2.2 Gy) to a total of 60-72 Gy over approximately 7 weeks; Administered 80-100 mg/m2 once every three weeks for 3 doses or 30-40 mg/m2 once weekly for 6-7 doses.
Substitution of other systemic agents due to related toxicities (i.e., carboplatin) would be evaluated to determine eligibility by the Medical Monitor
Intervention MeSH terms: Avasopasem manganese
Phase: Phase 2
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 223.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: squamous cell carcinoma of the head and neck; oral cavity; oropharynx; intensity-modulated radiation therapy; chemotherapy; oral mucositis; superoxide dismutase; radioprotection

Summary:

      The purpose of the phase 2, GT-201 clinical study is to determine if GC4419 administered
      prior to intensity-modulated radiation therapy (IMRT) reduces the incidence, duration, and
      severity of radiation induced oral mucositis in patients who have been diagnosed with locally
      advanced, non-metastatic squamous cell carcinoma of the head and neck.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Pathologically-confirmed diagnosis of squamous cell carcinoma of the head and neck,
             defined as SCC of the oral cavity or oropharynx that will be treated with cisplatin
             plus concurrent IMRT Note: Patients with unknown primary tumors whose treatment plan
             matches the requirements specified in Inclusion Criteria #2 and #3 below are eligible
             for the trial.

          2. Treatment plan to receive a continuous course of IMRT delivered as 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 > 50 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. Treatment plan to receive standard cisplatin monotherapy administered either every
             three weeks (80-100 mg/m2 for 3 doses) or weekly (30-40 mg/m2 for 6-7 doses). The
             decision on which chemotherapy regimen to use in combination with IMRT and GC4419 will
             be at the discretion of the investigator.

          4. Age 18 years or older

          5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

          6. Adequate hematologic function as indicated by:

               -  Absolute neutrophil counts (ANC) ≥ 1,500/mm3

               -  Hemoglobin (Hgb) ≥ 9.0 g/dL

               -  Platelet count ≥ 100,000/mm3

          7. Adequate renal and liver function as indicated by:

               -  Serum creatinine acceptable for treatment with cisplatin per institutional
                  guidelines

               -  Total bilirubin ≤ 1.5 x upper-normal limit (ULN)

               -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN

               -  Alkaline phosphatase ≤ 2.5 x ULN

          8. Human papilloma virus (HPV) status in tumor has been documented using tumor
             immunohistochemistry for HPV-p16 or other accepted test

          9. Serum pregnancy test negative for females of childbearing potential

         10. Males and females must agree to use effective contraception starting prior to the
             first day of treatment and continuing for 30 days after the last dose of GC4419

         11. Properly obtained written informed consent

        Exclusion Criteria:

          1. Tumor of the lips, larynx, hypopharynx, nasopharynx, sinuses, or salivary glands

          2. Metastatic disease (Stage IV C)

          3. Prior radiotherapy to the region of the study cancer or adjacent anatomical sites or
             more than 25% of total body marrow-bearing area (potentially interfering with
             chemotolerance)

          4. Prior induction chemotherapy

          5. Receiving any approved or investigational anti-cancer agent other than those provided
             for in this study

          6. Participation in another clinical trial or use of another investigational agent within
             30 days of study entry

          7. Requirement for significantly modified diet (liquids and/or solids) due to compromised
             oral/pharyngeal function at baseline

          8. Requirement at baseline for parenteral or gastrointestinal tube-delivered nutrition
             for any reason

          9. Malignant tumors other than head and neck cancer (HNC) within the 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 (World Health Organization Score ≥ Grade 1) at study entry

         12. 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)

         13. Female patients who are pregnant or breastfeeding

         14. Known allergies or intolerance to cisplatin and similar platinum-containing compounds

         15. Requirement for concurrent treatment with nitrates or other drugs that may, in the
             judgment of the treating investigator, create a risk for a precipitous decrease in
             blood pressure