Amifostine With IMRT for Submandibular and Sublingual Salivary Sparing During Head and Neck Cancer Treatment
Condition: Head and Neck Cancer
MeSH terms: Head and Neck Neoplasms
Intervention: Amifostine; Intensity- Modulated Radiation Therapy
Intervention description: 500 mg in two divided doses subcutaneously given 30-60 minutes prior to IMRT.; 2.0 to 2.2 Gy delivered in 30 fractions
Intervention MeSH terms: Amifostine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Head and Neck Cancer; HNSCC; Submandibular and Sublingual Salivary Sparing; Amifostine; Ethyol; Radiation Therapy

Summary:

      Primary Objective:

      To determine if amifostine in combination with IMRT can mitigate the decrease in production
      of saliva by the submandibular and sublingual salivary glands in patients with HNSCC.

      Secondary Objectives:

        1. To establish a parotid gland dose volume histogram (DVH) versus measured flow
           relationship in this patient population:

             -  When the mean dose is < 24-26 Gy (shift recovery time to left)

             -  When the mean dose is > 24-26 Gy (DVH shift)

        2. To observe mucositis in the following lower dose RT areas:

             -  Upper lip

             -  Lower lip

             -  Right cheek

             -  Left cheek

             -  Right ventral and lateral tongue

             -  Left ventral and lateral tongue

             -  Floor of the mouth

             -  Soft palate

             -  Hard palate.

        3. To observe the incidence and patterns of occipital scalp epilation;

        4. To observe the incidence of dysphagia using the List Performance Status Scale (LPSS);
           and

        5. To further evaluate the safety profile of amifostine in this patient population.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Adult men and women of at least 18 years of age at the time of patient entry;

          2. Women of reproductive potential (defined as being <1 year post-menopausal) must have a
             negative serum pregnancy test within 7 days of study entry;

          3. Men and women of reproductive potential must agree to practice an effective method of
             avoiding pregnancy (including oral or implanted contraceptives, intrauterine device
             (IUD), female condom, diaphragm with spermicide, cervical cap, use of a condom by the
             sexual partner or sterile sexual partner) beginning at the time the informed consent
             is signed, and must agree to continue using such precautions while receiving IMRT
             through 6 weeks after the last dose of amifostine or RT, whichever is the last therapy
             discontinued;

          4. Patients undergoing definitive or post-operative IMRT as follows:

          5. Definitive Patients: Histology confirmed unknown primary T0N1-2bM0 or oropharynx Stage
             I, II, III, IV (TX, T1-T2, favorable T3 (exophytic) N0-N2b, M0), small volume primary
             and nodal, not requiring chemotherapy during RT (i.e., induction chemo is acceptable
             as well as concurrent biological therapy e.g., Cetuximab), squamous cell carcinoma
             (AJCC Staging of HNSCC). Lymph nodes bilaterally of the neck are at risk for
             metastatic disease and require irradiation per clinical judgment.

          6. Post-operative Patients: Histology confirmed oral cavity, oropharynx, larynx and
             hypopharynx squamous cell carcinoma (AJCC Staging of HNSCC): *Stage III and IV
             squamous cell carcinoma treated with surgery as the primary modality requiring
             post-operative RT, but not receiving concurrent chemotherapy. *Indications for
             post-operative RT include: unfavorable T3 and T4 primaries, compromised margins, nodal
             metastases, extracapsular nodal extension, perineural invasion and lymphovascular
             invasion.

          7. Zubrod performance status of 0 or 1

          8. Adequate nutritional status as determined by the treating physician in conjunction
             with consultation with clinical nutritionists, as indicated.

          9. Hemoglobin must be greater than or equal to 10 g/dL.

         10. At least one parotid should keep a mean RT dose of < 24-26 Gy. If this cannot be
             achieved on one side, then the contralateral parotid dosing goal is to keep the mean
             dose as low as possible, typically <15 Gy.

         11. It is anticipated that at least one submandibular gland will receive a mean dose
             >24-26 Gy.

         12. Written informed consent and HIPAA authorization obtained from the patient prior to
             receipt of any study medication or beginning study procedures.

        Exclusion Criteria:

          1. Evidence of significant wound infection, fistula, or major wound dehiscence at time of
             patient entry.

          2. Carcinomas of the paranasal sinuses, nasopharynx, or N3 at time of patient entry.

          3. Presence of prior malignancies <5 years other than non-melanoma skin cancer or
             cervical, breast or bladder cancer in situ.

          4. T3N0 glottic cancer at time of patient entry.

          5. Prior chemotherapy for other cancer within less than or equal to 3 years prior to
             patient entry.

          6. Planned concurrent or adjuvant chemotherapy.

          7. Less than gross total resection for patients on post-operative RT.

          8. Prior head neck irradiation except for localized non-melanomatous cutaneous
             carcinomas.

          9. Salivary gland disease, e.g. Sjogren's disease at time of patient entry.

         10. Pregnant or nursing at the time of patient entry or positive serum pregnancy test
             within 7 days of study entry.

         11. Use of pilocarpine or cevimeline during participation in the study.

         12. General medical or psychological conditions that might preclude the patient from
             completion of the study or from understanding and signing the informed consent.

         13. Evidence of distant metastases.