Clinical trial NCT00006106: ONYX-015 With Cisplatin and Fluorouracil in Treating Patients With Advanced Head and Neck Cancer
Official title: Phase I Study of Intraarterial ONYX-015 in Combination With Intravenous Cisplatin and Fluorouracil in Patients With Advanced Squamous Cell Cancer of the Head and Neck
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Lip and Oral Cavity Cancer
Head and Neck Cancer
Oropharyngeal Cancer
Keywords: adult solid tumor
body system/site cancer
cancer
cellular diagnosis, hypopharyngeal cancer
cellular diagnosis, laryngeal cancer
cellular diagnosis, lip and oral cavity cancer
cellular diagnosis, nasopharyngeal cancer
cellular diagnosis, oropharyngeal cancer
cellular diagnosis, paranasal sinus and nasal cavity cancer
head and neck cancer
hypopharyngeal cancer
hypopharyngeal squamous cell carcinoma
laryngeal cancer
laryngeal squamous cell carcinoma
lip and oral cavity cancer
lip and oral cavity squamous cell carcinoma
metastatic squamous neck cancer with occult primary
nasopharyngeal cancer
nasopharyngeal squamous cell carcinoma
oropharyngeal cancer
oropharyngeal squamous cell carcinoma
paranasal sinus and nasal cavity cancer
paranasal sinus and nasal cavity squamous cell carcinoma
recurrent hypopharyngeal cancer
recurrent laryngeal cancer
recurrent lip and oral cavity cancer
recurrent metastatic squamous neck cancer with occult primary
recurrent nasopharyngeal cancer
recurrent oropharyngeal cancer
recurrent paranasal sinus and nasal cavity cancer
recurrent squamous cell carcinoma of the hypopharynx
recurrent squamous cell carcinoma of the larynx
recurrent squamous cell carcinoma of the lip and oral cavity
recurrent squamous cell carcinoma of the nasopharynx
recurrent squamous cell carcinoma of the oropharynx
recurrent squamous cell carcinoma of the paranasal sinus and nasal cavity
solid tumor
stage III hypopharyngeal cancer
stage III laryngeal cancer
stage III lip and oral cavity cancer
stage III nasopharyngeal cancer
stage III oropharyngeal cancer
stage III paranasal sinus and nasal cavity cancer
stage III squamous cell carcinoma of the hypopharynx
stage III squamous cell carcinoma of the larynx
stage III squamous cell carcinoma of the lip and oral cavity
stage III squamous cell carcinoma of the nasopharynx
stage III squamous cell carcinoma of the oropharynx
stage III squamous cell carcinoma of the paranasal sinus and nasal cavity
stage IV hypopharyngeal cancer
stage IV laryngeal cancer
stage IV lip and oral cavity cancer
stage IV nasopharyngeal cancer
stage IV oropharyngeal cancer
stage IV paranasal sinus and nasal cavity cancer
stage IV squamous cell carcinoma of the hypopharynx
stage IV squamous cell carcinoma of the larynx
stage IV squamous cell carcinoma of the lip and oral cavity
stage IV squamous cell carcinoma of the nasopharynx
stage IV squamous cell carcinoma of the oropharynx
stage IV squamous cell carcinoma of the paranasal sinus and nasal cavity
stage, hypopharyngeal cancer
stage, laryngeal cancer
stage, lip and oral cavity cancer
stage, metastatic squamous neck cancer with occult primary
stage, nasopharyngeal cancer
stage, oropharyngeal cancer
stage, paranasal sinus and nasal cavity cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: Dana-Farber Cancer Institute
First posted: 2004-04-29
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: A specially modified virus called ONYX-015 may be able to kill tumor cells while leaving normal cells undamaged. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining ONYX-015 with chemotherapy may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of ONYX-015 combined with cisplatin and fluorouracil in treating patients who have advanced head and neck cancer.

Detailed description: OBJECTIVES:

I. Determine the feasibility and maximum tolerated dose (MTD) of intraarterial ONYX-015 in patients with advanced squamous cell cancer of the head and neck.

II. Determine the feasibility and tolerability of intraarterial ONYX-015 at the MTD OR maximum theraputic dose, whichever is lower, in combination with intravenous cisplatin and fluorouracil in these patients.

III. Determine the qualitative distribution of ONYX-015 within a limited tumor biopsy and a normal mucosal biopsy at different dose levels.

IV. Determine the response of these patients to intraarterial ONYX-015. V. Determine the response of these patients to cisplatin and fluorouracil following intraarterial ONYX-015.

PROTOCOL OUTLINE: This is a dose escalation study. Patients receive intraarterial infusions of ONYX-015. Treatment repeats once in 3-4 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-8 patients receive escalating doses of ONYX-015 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 5 patients experience dose limiting toxicity.

Patients in cohorts 1-4 are followed for 5 days after infusion, weekly for 3 weeks, at week 6, and monthly thereafter for 4 months.

A fifth or final cohort of 10 patients will receive ONYX-015 at the MTD. If the MTD was not determined in cohorts 1-4, patients receive the highest dose administered to cohort 4. Beginning 1-2 days after ONYX-015 infusion, patients receive cisplatin IV over 30-60 minutes once and fluorouracil IV continuously over 4 days. Treatment repeats in 4 weeks in the absence of disease progression or unacceptable toxicity. Cisplatin and fluorouracil IV treatment continues every 3-4 weeks at the discretion of the treating oncologist.

Patients in cohort 5 are followed for 5 days after initial infusion, weekly for 4 weeks, at week 8, and monthly thereafter for 4 months.

PROJECTED ACCRUAL:

A total of 23-28 patients will be accrued for this study.

Eligibility criteria: PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

* Histologically confirmed squamous cell carcinoma of the head and neck (SCCHN) that is incurable by standard therapy
* Measurable or evaluable disease
* Multiple SCCHN primaries allowed
* Metastases allowed if tumor to be treated is confined to head and neck region

--Prior/Concurrent Therapy--

* Biologic therapy: Recovered from prior biologic therapy
* Chemotherapy: At least 3 weeks since prior chemotherapy and recovered
* Endocrine therapy: Recovered from prior endocrine therapy
* Radiotherapy: At least 12 weeks since prior radiotherapy and recovered
* Surgery: Recovered from prior surgery
* Other: Recovered from any prior diagnostic or theraputic procedures

--Patient Characteristics--

* Age: 18 to physiologic 79
* Performance status: ECOG 0-2
* Life expectancy: Over 3 months
* Hematopoietic: WBC greater than 3,000/mm3 OR Absolute neutrophil count greater than 2,000/mm3; Platelet count greater than 100,000/mm3; Hemoglobin greater than 10 g/dL (transfusions allowed if not used solely to meet eligibility criteria)
* Hepatic: SGOT less than 2.5 times upper limit of normal (ULN); Alkaline phosphatase less than 3 times ULN; Bilirubin no greater than 1.5 times ULN
* Renal: Creatinine less than 1.6 mg/dL OR Creatinine clearance greater than 50 mL/min
* Cardiovascular: No active cardiovascular disease that would limit physical activity (i.e., ability to walk 50 feet without stopping)
* Pulmonary: No active pulmonary disease that would limit physical activity (i.e., ability to walk 50 feet without stopping)
* Other: No other prior or concurrent malignancy within the past 3 years except limited basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix; Adequate and nutritionally balanced enteral intake of at least 1,800 kcal/day (enteral feeding tube dependent allowed); No intravenous alimentation as primary source of calories; No other serious illness or medical condition that would preclude study (i.e., active systemic lupus erythematosus, Crohn's disease or AIDS); No prior immunodeficiency (i.e., HIV infection, organ transplant, or chronic steroid use); Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective contraception

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Marshall R. Posner
role: STUDY_CHAIR
References: