Randomized Amifostine For SCCHN

Dana-Farber Cancer Institute

Status and phase: Completed; Phase 2

Conditions: Chemotherapeutic Agent Toxicity; Xerostomia; Radiation Toxicity; Head and Neck Cancer; Mucositis

Treatments: Drug: Carboplatin; Radiation: radiation; Drug: Paclitaxel; Drug: Amifostine

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT00095927

P30CA006516 (U.S. NIH Grant/Contract)

03018

Details and patient eligibility

About

This research study is studying a drug called Amifostine as a treatment for squamous cell carcinoma in the head and/or neck area.

Full description

Amifostine is a drug that is used to treat moderate to severe xerostomia (dry mouth) for those who receive radiation therapy for head and neck cancer. It was approved by the FDA for use intravenously. This study plans to examine the effects of xerostomia when Amifostine is used subcutaneously (by injection). Amifostine has been seen to be effective when used to combat the effects of dry mouth, but also has some side effects which are listed later in this consent form.

The purpose of this study is to examine the effectiveness of twice a day radiation therapy given with chemotherapy consisting of carboplatin and paclitaxel (Taxo 1). This study will examine the effectiveness of adding Amifostine in the hopes of reducing the side effects of radiation.

Enrollment: 58 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

• Histologically or cytologically proven squamous cell carcinoma of the head and neck. Biopsy is preferred unless medically contraindicated.

• Primary tumor sites eligible: oral cavity, oropharynx, hypopharynx or larynx. Tumors of the nasal and paranasal cavities will also be included. Unknown primary SCC in the neck will also be eligible.

• Stage 2, 3 or 4 disease without evidence of distant metastases verified by chest X-Ray, abdominal ultrasound or CT (in case of liver function test abnormalities); bone scan in case of local symptoms.

• At least one uni- or bidimensionally measurable lesion at the start of all therapy (induction therapy ag well as chemoradiation).

• No previous head and neck radiotherapy and no previous curative surgery for SCCHN (other than biopsy) are allowed at time of study entry.

• Age ≥ 18 years.

• WHO performance status of 0 or 1 (section 13, Appendix I)

• No active alcohol addiction (as assessed by medical caregiver).

• Life expectancy ≥ 12 weeks.

• Signed informed consent prior to beginning protocol specific procedures.

• Adequate bone marrow, hepatic and renal functions as evidenced by the following:

  • Hematology:

    • neutrophil count ≥ 2.0 x 10 9/1.
    • platelet count ≥ 100 x 10 9/1.
    • hemoglobin ≥ 10 g/dl.

  • Hepatic function:

    • total bilinthin WNL.
    • ASAT (SGOT) and ALAT (SGPT) ≤ 2.5 x 1JLN.
    • alkaline phosphatase ≤ 5 x ULN.
    • patients with ASAT or ALAT > 1.5 x ULN associated with alkaline phosphatase > 2.5
    • x ULN are not eligible for the study.

  • Renal function: the creatinine clearance ≥ 60 ml/min (actual or calculated by the Cockcroft-Gault method as follows:

    • Weight(kg) x (140 - age)/K x serum creatinine

    • serum creatinine in mg/dL

      • K: 72 in man
      • K: 85 in woman

    • serum creatinine in µmon/L

      • K: 0.814 in man
      • K: 0.96 in woman

• Patients must be available for treatment and follow-up. Patients registered on this trial must be treated and followed at the participating centers

• Previous chemotherapy is permitted, provided that it is in induction form before starting radiation therapy and that it is being used to treat head and neck cancers.

Exclusion Criteria:

• Pregnant or lactating women, or women of childbearing potential not using adequate contraception.

• Previous or current malignancies at other sites, with the exception of adequately treated in situ carcinoma of the cervix uteri, basal or squamous cell carcinoma of the skin or other cancer curatively treated by surgery and with no evidence of disease for at least 3 years.

• Symptomatic peripheral neuropathy ≥ grade 2 by NCIC-CTG criteria.

• Other serious illnesses or medical conditions including but not limited to:

  • Unstable cardiac disease despite treatment, myocardial infarction within 6 months prior to study entry
  • History of significant neurologic or psychiatric disorders including dementia or seizures.
  • Active uncontrolled infection.
  • Active peptic ulcer.
  • Hypercalcemia.
  • Chronic obstructive pulmonary disease requiring hospitalization during the year preceding study entry.

• Patients requiring intravenous alimentation.

• Patients who experienced a weight loss of more than 20% of their body weight in the 3 months preceding study entry (unless purposeful)

• Concurrent treatment with any other anticancer therapy.

• Participation in an investigational trial within 30 days of study entry.

• Previous treatment with any biologic therapy is not permitted.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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58 participants in 2 patient groups

Arm A Amifostine

Active Comparator group

Description:

Patients with newly diagnosed, locally advanced stage ill or IV SCCHN received; * 4 weekly doses of carboplatin (area under the curve, 1.5) and paclitaxel (45 mg/m 2) concurrently with concomitant boost radiation consisting of 72 grays in 42 fractions over 6 weeks (every day for 18 days, twice a day for 12 days) (grading determined according to the TNM staging system). * Subcutaneous daily amifostine at a dose of 500 mg

Treatment:

Drug: Amifostine

Radiation: radiation

Drug: Paclitaxel

Drug: Carboplatin

Arm B No-Amifostine

Experimental group

Description:

Patients with newly diagnosed, locally advanced stage ill or IV SCCHN - 4 weekly doses of carboplatin (area under the curve, 1.5) and paclitaxel (45 mg/m 2) concurrently with concomitant boost radiation consisting of 72 grays in 42 fractions over 6 weeks (every day for 18 days, twice a day for 12 days) (grading determined according to the TNM staging system).

Treatment:

Radiation: radiation

Drug: Paclitaxel

Drug: Carboplatin