Palifermin in Lessening Oral Mucositis in Patients Undergoing Radiation Therapy and Chemotherapy for Locally Advanced Head and Neck Cancer
Condition: Head and Neck Cancer; Mucositis; Pain; Radiation Toxicity
MeSH terms: Head and Neck Neoplasms; Mucositis; Stomatitis
Intervention: palifermin; cisplatin; placebo; neck dissection; radiation therapy
Intervention description: Four doses of palifermin, 180ųg/kg, administered as an i.v. bolus injection over 30-60 seconds. Starting on day -3 (Friday) prior to radiation therapy / chemotherapy and then once weekly, on days 5, 12, and 19.; Patients will receive cisplatin (100 mg/m2) administered intravenously on days 1, 22, and 43 of the treatment course.; Four doses of placebo, 180ųg/kg, administered as an i.v. bolus injection over 30-60 seconds. Starting on day -3 (Friday) prior to radiation therapy / chemotherapy and then once weekly, on days 5, 12, and 19.; A neck dissection is required for patients with persistent nodal disease, any stage, if a palpable abnormality or worrisome radiographic abnormality persists in the neck 8-9 weeks after completion of therapy. A neck dissection is optional for patients with multiple positive lymph nodes or with lymph nodes exceeding 3 cm in diameter at pre-treatment (N2a, N2b, N3) who achieve a complete clinical and radiographic response in the neck. All patients will be assessed at approximately 8 weeks post-treatment with CT scan or MRI by the same technique used at baseline.; A radiation dose of 70 Gy with at least 66 Gy to at least 2 mucosal sites of the oral cavity/oropharynx mucosa. Radiation therapy can be given with 3D conformal (3D-CRT) or with intensity modulated RT (IMRT) techniques; however, the chosen modality must be used for the entire course of treatment.
Intervention MeSH terms: Cisplatin
Phase: Phase 3
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: mucositis; pain; radiation toxicity; stage III squamous cell carcinoma of the hypopharynx; stage IV squamous cell carcinoma of the hypopharynx; stage III squamous cell carcinoma of the larynx; stage IV squamous cell carcinoma of the larynx; stage III squamous cell carcinoma of the lip and oral cavity; stage IV squamous cell carcinoma of the lip and oral cavity; stage III squamous cell carcinoma of the oropharynx; stage IV squamous cell carcinoma of the oropharynx

Summary:

      RATIONALE: Growth factors, such as palifermin, may lessen the severity of mucositis, or mouth
      sores, in patients receiving radiation therapy and chemotherapy for head and neck cancer. It
      is not yet known whether palifermin is more effective than a placebo in lessening mucositis
      in patients receiving radiation therapy and chemotherapy for head and neck cancer.

      PURPOSE: This randomized phase III trial is studying palifermin to see how well it works
      compared to a placebo in lessening oral mucositis in patients undergoing radiation therapy
      and chemotherapy for locally advanced head and neck cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Pathologically (histologically or cytologically) proven (from primary lesion and/or
             lymph nodes) diagnosis of squamous cell carcinoma of the oral cavity, oropharynx,
             hypopharynx, or larynx;

          2. Patients must have at least 2 mucosal sites of the oral cavity/oropharynx mucosa
             assessable by visual transoral inspection that will receive at least 66 Gy;

             -2.1 Patients with tumors of the larynx or hypolarynx are eligible only if it is
             anticipated that the 2 index sites in the oral cavity/oropharynx mucosa will receive
             at least 66 Gy;

          3. Patients must be able to be evaluated for the primary endpoint; therefore, patients
             must be able to eat at least soft solids and not require a feeding tube for nutrition
             or hydration at study entry.

          4. Selected Stage III (excluding T1N1MO) or IVA-B (AJCC, 6th edition) at study entry,
             including no distant metastases, based upon the following minimum diagnostic workup:

               -  4.1 History/physical examination, including documentation of tobacco/alcohol use
                  and current medications (including opioids/dosing), within 8 weeks prior to
                  registration;

               -  4.2 Chest x-ray (or Chest CT scan) within 6 weeks prior to registration;

               -  4.3 MRI or CT scan with contrast of tumor site within 6 weeks prior to
                  registration;

               -  4.4 Assessment of mucositis and xerostomia within 2 weeks prior to registration;

          5. Zubrod Performance Status 0-1;

          6. Age > 18;

          7. Adequate bone marrow function, defined as follows:

               -  7.1 Absolute neutrophil count (ANC) > 1,800 cells/mm3 based upon CBC/differential
                  obtained within 2 weeks prior to registration on study

               -  7.2 Platelets > 100,000 cells/mm3 based upon CBC/differential obtained within 2
                  weeks prior to registration on study

               -  7.3 Hemoglobin > 8.0 g/dl based upon CBC/differential obtained within 2 weeks
                  prior to registration on study (Note: The use of transfusion or other
                  intervention to achieve Hgb > 8.0 g/dl is acceptable.)

          8. Adequate hepatic function with bilirubin < 1.5 mg/dl, AST or ALT < 2 x ULN within 2
             weeks prior to registration;

          9. Adequate renal function with serum creatinine < 1.5 mg/dl and creatinine clearance
             (CC) ≥ 50 ml/min within 2 weeks prior to registration determined by 24-hour collection
             or estimated by Cockcroft-Gault formula:

             CCr male = [(140 - age) x (wt in kg)]/[(Serum Cr mg/dl) x (72)] CCr female = 0.85 x
             (CrCl male)

         10. Normal serum calcium or normal corrected serum calcium within 2 weeks prior to
             registration; formula for corrected calcium if albumin valued is below normal range:
             Corrected calcium (mg/dl) = (4 - [patient's albumin (g/dl)] x 0.8) + patient's
             measured calcium (mg/dl);

         11. Serum pregnancy test for women of childbearing potential within 2 weeks prior to
             registration;

         12. Women of childbearing potential and male participants must practice adequate
             contraception.

         13. Patient agrees to refrain from using all products listed in Section 9.2,
             "Non-permitted Supportive Therapy";

         14. Patient must sign study specific informed consent prior to study entry.

        Exclusion Criteria:

          1. Patients with a history of prior head and neck squamous cancer are ineligible;

          2. Stage IVC (AJCC, 6th edition) [Any T, Any N, M1] or distant metastases at protocol
             study entry; T1N1M0 patients are excluded.

          3. Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free
             for a minimum of 3 years;

          4. Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a
             different cancer is allowable. See Sections 1 and 3.

          5. Prior radiotherapy to the region of the study cancer that would result in overlap of
             radiation therapy fields;

          6. Initial surgical treatment, excluding diagnostic biopsy of the primary site or nodal
             sampling of neck disease; radical or modified neck dissection is not permitted.

          7. Severe, active co-morbidity, defined as follows:

               -  7.1 Symptomatic and/or uncontrolled cardiac disease, New York Heart Association
                  Classification III or IV (see Appendix II);

               -  7.2 Transmural myocardial infarction within the last 6 months;

               -  7.3 Acute bacterial or fungal infection requiring intravenous antibiotics at the
                  time of registration;

               -  7.4 Chronic Obstructive Pulmonary Disease exacerbation or other respiratory
                  illness requiring hospitalization or precluding study therapy at the time of
                  registration.

               -  7.5 Hepatic insufficiency resulting in clinical jaundice and/or coagulation
                  defects;

               -  7.6 Patients known to be sero-positive for hepatitis B virus (HBV) or hepatitis C
                  virus (HCV);

               -  7.7 Patients known to be sero-positive for human immunodeficiency virus (HIV) or
                  patients with Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC
                  definition; note, however, that HIV testing is not required for entry into this
                  protocol. The need to exclude patients with HIV or AIDS from this protocol is
                  necessary because the treatments involved in this protocol may be significantly
                  immunosuppressive.

               -  7.8 A history of pancreatitis.

          8. Collagen vascular disease, such as scleroderma, as this disease is thought to
             predispose patients to increased risk for radiation-associated toxicities;

          9. Previous treatment with palifermin or other keratinocyte growth factors, such as
             velafermin or repifermin;

         10. Prior allergic reaction or known sensitivity to any of the agents administered during
             dosing, including E. coli-derived products, such as Nutropin®, Neupogen®, Humulin®,
             Roferon®; Neumega®, Neulasta®), IntronA®, Betaseron®;

         11. Pregnancy or women of childbearing potential and men who are sexually active and not
             willing/able to use medically acceptable forms of contraception; this exclusion is
             necessary because the treatment involved in this study may be significantly
             teratogenic.