Gemcitabine and Doxorubicin in Treating Patients With Recurrent or Progressive Head and Neck Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as gemcitabine and doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving gemcitabine together with doxorubicin works in treating patients with recurrent or progressive head and neck cancer.

Official Title
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A Phase II Study of Gemcitabine in Combination With Doxorubicin for Patients With Head and Neck Cancer

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Drug: doxorubicin hydrochloride
* Drug: gemcitabine hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Inclusion criteria: Histologically or cytologically confirmed head and neck cancer Recurrent or progressive disease Must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm by conventional techniques or as ≥ 10 mm by spiral CT scan Must have received prior platinum-based chemotherapy regimen (cisplatin or carboplatin) with or without radiotherapy, unless the patient was deemed unsuitable for platinum-based therapy due to renal dysfunction or other clinical contraindication Exclusion criteria: Known brain metastases PATIENT CHARACTERISTICS: Inclusion criteria: ECOG performance status (PS) ≤ 2 OR Karnofsky PS ≥ 60% Absolute neutrophil count ≥ 1,500/μL Platelets ≥ 100,000/µL Total bilirubin ≤ 1.5 mg/dL AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal Creatinine ≤ 2 mg/dL OR creatinine clearance ≥ 30 mL/min Females of reproductive potential must not plan on conceiving children during study treatment period and must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of the study Exclusion criteria: Not pregnant or breastfeeding History of allergic reaction attributed to compounds of similar chemical or biological composition to gemcitabine hydrochloride or doxorubicin hydrochloride Lower than normal cardiac ejection fraction Patients must have an echocardiogram or MUGA scan prior to the use of study drugs Uncontrolled intercurrent illness that would limit compliance with study requirements including, but not limited to, any of the following: Ongoing or active infection Symptomatic congestive heart failure Unstable angina pectoris Cardiac arrhythmia Psychiatric illness or social situation Clinical AIDS or known positive HIV serology PRIOR CONCURRENT THERAPY: Inclusion criteria: Recovered from prior therapy At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) At least 30 days since prior experimental agents At least 4 weeks since prior radiotherapy for palliation or for the primary tumor Exclusion criteria: Prior gemcitabine hydrochloride or doxorubicin hydrochloride Concurrent hormones or other chemotherapeutic agents, except for steroids given for adrenal failure, hormones given for non-disease-related conditions (e.g., insulin for diabetes), or intermittent use of dexamethasone as an antiemetic Concurrent palliative radiotherapy Other concurrent investigational or commercial agents or therapies

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gemcitabine+doxorubicin<br> | Drug: doxorubicin hydrochloride<br>* given as 25mgm2 IV on days 1 and 8 of each 21-day cycle.<br>Drug: gemcitabine hydrochloride<br>* given as 100mg/m2 IV over days 1 and 8 of each 21 day cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate | Per Response Evaluation Criteria in Solid Tumors (RECIST) for target lesions assessed by CT or MRI: Complete Response (CR) is the disappearance of all target lesions (TL) and non-target lesions (NTL); Partial Response (PR) is defined by either a CR of TL and stable disease (SD) in NTL or PR of TL and non-progressive disease (PD) in NTL. Response rate is the sum of CR + PR as defined above. | Every 6 weeks from the time of initial treatment for up to 8 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response |  | Every 6 weeks for up to 8 months | 
| Progression-free Survival |  | Through the end of follow up, for an average of 8 months | 
| Overall Survival |  | From the time of initial therapy until the time of death. | 
| Number of Patients Who Had Greater Than Grade 2 Toxicity |  | from time of initial treatment until end of study, an average of 6 months | 
| Correlation of Cytoxocity With Cell-cycle Arrest |  | prior to first dose of drug and every 6 weeks up to 6 months | 
| Correlation of Cytotoxicity With Apoptosis in Cancer Cells |  | prior to first dose of drug and every 6 weeks for up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent squamous cell carcinoma of the hypopharynx, recurrent squamous cell carcinoma of the larynx, recurrent verrucous carcinoma of the larynx, recurrent adenoid cystic carcinoma of the oral cavity, recurrent basal cell carcinoma of the lip, recurrent mucoepidermoid carcinoma of the oral cavity, recurrent squamous cell carcinoma of the lip and oral cavity, recurrent verrucous carcinoma of the oral cavity, recurrent metastatic squamous neck cancer with occult primary, recurrent lymphoepithelioma of the nasopharynx, recurrent squamous cell carcinoma of the nasopharynx, recurrent esthesioneuroblastoma of the paranasal sinus and nasal cavity, recurrent inverted papilloma of the paranasal sinus and nasal cavity, recurrent midline lethal granuloma of the paranasal sinus and nasal cavity, recurrent squamous cell carcinoma of the paranasal sinus and nasal cavity, recurrent salivary gland cancer, recurrent lymphoepithelioma of the oropharynx, recurrent squamous cell carcinoma of the oropharynx