Clinical trial NCT00095927: Randomized Amifostine For SCCHN
Official title: Phase II, Randomized Study of Concomitant Chemoradiation Using Weekly Carboplatinum/Paclitaxel With (Arm A) or Without (Arm B) Daily Subcutaneous Amifostine in Patients With Newly Diagnosed Locally Advanced Squamous Cell Cancer of the Head and Neck
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chemotherapeutic Agent Toxicity
Head and Neck Cancer
Mucositis
Radiation Toxicity
Xerostomia
Keywords: radiation toxicity
chemotherapeutic agent toxicity
mucositis
xerostomia
stage II squamous cell carcinoma of the lip and oral cavity
stage III squamous cell carcinoma of the lip and oral cavity
stage IV squamous cell carcinoma of the lip and oral cavity
stage II squamous cell carcinoma of the oropharynx
stage III squamous cell carcinoma of the oropharynx
stage IV squamous cell carcinoma of the oropharynx
stage II squamous cell carcinoma of the hypopharynx
stage III squamous cell carcinoma of the hypopharynx
stage IV squamous cell carcinoma of the hypopharynx
stage II squamous cell carcinoma of the larynx
stage III squamous cell carcinoma of the larynx
stage IV squamous cell carcinoma of the larynx
stage II squamous cell carcinoma of the paranasal sinus and nasal cavity
stage III squamous cell carcinoma of the paranasal sinus and nasal cavity
stage IV squamous cell carcinoma of the paranasal sinus and nasal cavity
untreated metastatic squamous neck cancer with occult primary
metastatic squamous neck cancer with occult primary squamous cell carcinoma
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: MedImmune LLC
name: AstraZeneca
First posted: 2004-11-09
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed 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.

Eligibility 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.

Primary outcomes:
measure: Rate of local/regional control (LRC) 1 year after beginning treatment
timeFrame: One year after beginning of treatment
measure: Proportion of patients with grade 2 or 3 chronic xerostomia at 3, 6 months
timeFrame: 3, 6 Months
measure: Proportion of patients with grade 3 and 4 mucositis as assessed by RTOG criteria once weekly during and after completion of radiotherapy
timeFrame: End of Radiotherapy
measure: Median duration of dependence on percutaneous endoscopic gastrectomy (PEG) for adequate nutrition at 8, 12, 24, and 52 weeks after completion of study treatment
timeFrame: 8,12, 24 and 52 weeks
Secondary outcomes:
measure: Duration of grade 3 and 4 mucositis once weekly during treatment and at 8, 12, 24, and 52 weeks after completion of study treatment
timeFrame: 8, 12, 24, and 52 weeks
measure: Proportion of patients with PEG dependency
timeFrame: 3, 6, and 12 months after completion of study treatment
measure: Time to disease progression
timeFrame: baseline to disease progression
measure: Quality of life as assessed by Functional Assessment of Cancer Therapy for Head and Neck Cancer (FACT-H&N) Survey
timeFrame: baseline, 8, 12, 24, and 52 weeks after completion of study treatment
measure: LRC and overall survival at 2 years after completion of study treatment
timeFrame: 2 Years after completion of study treatment
measure: Swallowing function
timeFrame: 2 years Post treatment
Other outcomes:
Locations:
city: Sanford
country: United States
facility: Goodall Hospital
state: Maine
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Concord
country: United States
facility: Bethke Cancer Center at Emerson Hospital
state: Massachusetts
city: Danvers
country: United States
facility: Mass General/North Shore Cancer Center
state: Massachusetts
city: Fall River
country: United States
facility: Saint Anne's Hospital - Fall River
state: Massachusetts
city: Lowell
country: United States
facility: Lowell General Hospital
state: Massachusetts
city: Dover
country: United States
facility: Wentworth Douglass Hospital
state: New Hampshire
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Robert I. Haddad, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Haddad R, Sonis S, Posner M, Wirth L, Costello R, Braschayko P, Allen A, Mahadevan A, Flynn J, Burke E, Li Y, Tishler RB. Randomized phase 2 study of concomitant chemoradiotherapy using weekly carboplatin/paclitaxel with or without daily subcutaneous amifostine in patients with locally advanced head and neck cancer. Cancer. 2009 Oct 1;115(19):4514-23. doi: 10.1002/cncr.24525.