A PHASE II RANDOMIZED, DOUBLE BLIND, PLACEBO CONTROLLED, MULTICENTRE COMPARATIVE STUDY OF ZD1839 250 MG OR 500 MG (IRESSA^TM) GIVEN EITHER CONTINUOUSLY OR CONCOMITANTLY WITH CISPLATIN PLUS RADIOTHERAPY FOR THE TREATMENT OF PATIENTS WITH PREVIOUSLY UNTREATED UNRESECTED LATE STAGE III/IV NON-METASTATIC HEAD AND NECK SQUAMOUS CELL CARCINOMA
UTSW IRB# 082004-015
Principal Investigator:  Phuc Nguyen, MD
Coordinator:   Allison Rodarte
Contact Number: (214) 648-5536

OBJECTIVES:The purpose of this research is to see if ZD1839 increases the effectiveness of treating head and neck cancer when given in addition to a standard treatment of radiotherapy (X-rays) and chemotherapy (cancer drugs). The use of chemoradiation is considered the standard therapy for this condition and this therapy will last for 7 weeks, however the overall study will last for 2 years.

This research is being done because we may find out more information regarding the activity of proteins called receptors which are located at the surface of the cancer cells is important in stimulating growth of many tumors.  ZD1839 is a drug that blocks one of these receptors called the Epidermal Growth Factor receptor (EGFR) that is commonly found in many tumor types (i.e. lung, breast or colon tumors) but especially in head and neck cancers. Laboratory experiments show that ZD1839 prevents many types of tumors from growing and shrinks some tumor types including those of the head and neck. 
Number of Participants:  National: 224  and Local: 15

KEY INCLUSION CRITERIA:

• Provision of written informed consent
• Female or male patients aged 18 years and over
• Patients must have measurable disease according to RECIST
• Presence of stage III or IVA (Appendix L) squamous cell carcinoma of the head and neck confirmed histologically by biopsy or by fine needle aspiration at the time of diagnosis
• No previous surgery to the tumour except for biopsy and not scheduled for surgery
• No previous chemotherapy or radiotherapy for any neoplasm/tumour
• No previous anti-EGFR therapy
• Life expectancy > 12 weeks
• World Health Organisation (WHO) Performance Status of 0 or 1.  Patients must be fully active or restricted in physically strenuous activity but able to do light work (e.g. light housework, office work).

KEY EXCLUSION CRITERIA:

• Buccal mucosal carcinomas and post-nasal space (nasopharyngeal carcinoma), thyroid, sinus or salivary gland tumours and Grade III laryngeal carcinoma
• Early stage III cancers (T1N1 or T2N1), Extensive disease (T4b) or metastatic disease (M1)
• Disease invading the mandible
• The presence of simultaneous primary tumours
• Known severe hypersensitivity to ZD1839 or any of the excipients of this product
• Known severe hypersensitivity to cisplatin or any of the excipients of this product
• Any evidence of clinically active interstitial lung disease (patients with chronic, stable, radiographic changes who are asymptomatic need not be excluded)
• Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal cell carcinoma or cervical cancer in situ
• Absolute neutrophil counts (ANC) <1.0 x 109/litre (L) or platelets < 100 x 109/L
• Serum bilirubin > 3 times the upper limit of the reference range (ULRR)
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >5 times the ULRR
• Calculated creatinine clearance (Cockcroft and Gault) < 60 ml/min
• Serum calcium above the ULRR
• As judged by the investigator, any evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory, cardiac, hepatic or renal disease)
• Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study
• Pregnancy or breastfeeding
• Concomitant use of phenytoin, carbamazepine, barbiturates, rifampicin, amifostine, erythropoietin or St. John’s Wort
• Concomitant use of CYP3A4 inhibitors (e.g., itraconazole)
• Treatment with a non-approved or investigational drug within 30 days before Day 1 of study treatment
• Evidence of ototoxicity or other neurotoxicity
• Concurrent treatment with other experimental drugs and/or anticancer agents

RTOG 0234 - A PHASE II RANDOMIZED TRIAL OF SURGERY FOLLOWED BY CHEMORADIOTHERAPY PLUS C225 (CETUXIMAB) FOR ADVANCED SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK
UTSW IRB# 092004-029
Principal Investigator:  Phuc Nguyen, MD
Coordinator:  Carolyn Zwartjes
Contact Number: (214) 648-5536

OBJECTIVES: A standard form of treatment for advanced head and neck cancer patients is surgery under general anesthesia followed by radiation therapy. However, in some patients, the cancer will come back even though they have surgery and radiation. This study is being done because we do not know which of the radiation, C225, and chemotherapy combinations being studied may better control advanced squamous cell carcinoma of the head and neck, or have fewer side effects, or prevent the cancer from coming back. In addition, if the patient agrees, blood tests, head and neck CT scan or MRI, and chest x-rays will be performed on the tumor following surgery to analyze growth patterns that may help to predict and treat head and neck cancer patients in the future.
Number of Participants:  National: 230  and Local: 10-15

KEY INCLUSION CRITERIA:

• AJCC pathological stage III or IV (note that the preoperative clinical stage may be I-IV) squamous cell carcinoma of the head and neck meeting the following criteria:  Gross total resection comleted with pathology demonstrating one of more of the following risk factors: Histologic extracapsular nodal extension; Histologic involvement of > 2 regional lymph nodes; Mucosal margin of resection with invasive cancer (limited to microscopic detection only)
• Site of tumor origin in the oral cavity, oropharynx, larynx, or hypopharynx (excluding lip, nasopharynx, or sinuses)
• Zubrod performance status of 0-1
• Pretreatment evaluations required for eligibility include: History and physical  examination within four weeks prior to study entry; Dental evaluation with management prior to start of radiation; Medical oncology examination to evaluate medical contraindications prior to start of chemotherapy; Surgical evaluation and clearance prior to start of RT
• Laboratory studies within four weeks prior to study entry: CBC with differential and platelet counts; serum chemistry tests to include sodium, potassium, glucose, calcium, magnesium, BUN, serum creatinine, total protein, albumin, alkaline phosphatase, total  bilirubin, AST and ALT;  Serum pregnancy test, if applicable, within one week prior to  study entry; urine dipstick test on the first day of treatment.
• Pre-operative CT or MRI of the primary tumor and neck for clinical staging is required
• Chest x-ray or thoracic CT scan within 90 days prior to study entry
• ANC > 2,000 mm³; platelets > 100,000/mm³; hemoglobin > 8.0g/dl; bilirubin < 1.5 X ULIN; serum creatinine < 1.5 mg/dl; AST and ALT and alkaline phosphates must be within the range allowing for eligibility,as in the following table:

• Patients must be > 18 years of age
• Women of childbearing potential (WOCBP) and male participants must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter
• Pregnant or lactating women are ineligible as treatment involves unforeseeable risks to the participant and to the embryo or fetus. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [hCG], or in accordance with local regulations, which ever is more sensitive)
• Patients must sign a study-specific informed consent form prior to registration.

KEY EXCLUSION CRITERIA:

• Histology positive for other than squamous cell carcinoma or lymphoepithelioma
• Evidence of distant metastases
• Less than gross total resection or patients requiring staged surgery
• Prior head and neck radiotherapy; prior cytotoxic chemotherapy, unless disease free > 3 years
• Active cardiac disease defined as unstable angina, uncontrolled hypertension, myocardial infarction in the last six months (unless successfully treated with CABG or PTCA), uncontrolled arrhythmia, or congestive heart failure; > 3 heart-related hospitalizations in the past year
• Severe COPD requiring > 3 hospitalizations over the past year
• Women of childbearing potential (WOCBP) and male participants who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 3 months after the study
• Pre-existing > Grade 2 peripheral neuropathy
• Uncontrolled seizure disorder or active neurological disease
• Prior invasive malignancy (excluding non-melanoma skin cancer) within the previous 3 years
• Prior anti-epidermal growth factor receptor antibody therapy or therapy with a tyrosine kinase inhibitor
• Patients with a history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80 must be excluded
• Presence of synchronous or concurrent head and neck primary tumors.

SCHEMA (3/16/05)

Pending: CETUXIMAB (GI05-92) - A PILOT STUDY WITH CETUXIMAB AND RADIATION THERAPY FOR PATIENTS WITH SURGICALLY RESECTABLE ESOPHAGEAL AND AND GE JUNCTION CARCINOMAS: HOOSIER ONCOLOGY GROUP STUDY
UTSW IRB# 042005-032
Principal Investigator:  Carlos Becerra, MD
Coordinator:  Allison Rodarte
Contact Number: (214) 648-5536

KEY INCLUSION CRITERIA:

• ECOG Performance Status of 0-2
• Pathological diagnosis of either squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal junction
• Clinical stage IIA, IIB or III esophageal or gastroesophageal junction squamous cell or adenocarcinoma without metastatic disease
• Patients must have tumor tissue available for assessment of EGFR status by IHC
  NOTE:  Patients with EGFR positive and negative tumors will be included.
• Patients must be surgical candidates and have no comorbid conditions or a performance status which would preclude them from having surgical resection of the primary tumor
• Patients must agree to surgery
• No prior use of radiation or chemotherapy for cancer of the esophagus or GE junction
• No prior therapy that specifically and directly targets the EGFR pathway (such as kinase inhibitors and antibodies directed against the HER family receptors)
• No major surgery within 28 days prior to being registered for protocol therapy
• No symptomatic brain metastasis.  A subject with prior brain metastasis may be considered if they have completed their treatment for brain metastasis, no longer require corticosteroids, and are asymptomatic
• Patients must have following laboratory parameters, obtained within 14 days prior to being registered for protocol therapy:
  • Absolute neutrophil count (ANC)  > 1,000 mm³
  • Platelet count  > 75,000 mm³
  • Hemoglobin  > 10g/dL
  • Creatinine  < 2.0 X institutional ULN
  • Bilirubin  < 2.5 X ULN
  • Aspartate aminotransferase AST (SGOT) or ALT (SGPT)1.5 X ULN
    
• Females of childbearing potential and males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) while on treatment and for a 3-month period thereafter.Females of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for protocol therapy.   Subjects are considered not of child bearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal
• Females must not be breastfeeding
• Age > 18 years at the time of consent
• No clinically significant infections as judged by the treating investigator
• No acute hepatitis or known HIV
• No other active malignancies
• No prior severe infusion reaction to a monoclonal antibody
• No concurrent chemotherapy not indicated in the study protocol or any other investigational agent (s).