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
18 Years
79 Years
Both
Lip and Oral Cavity Cancer, Head and Neck Cancer, Oropharyngeal Cancer
Trial Information
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
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Marshall R. Posner
Investigator Role:
Study Chair
Investigator Affiliation:
Dana-Farber Cancer Institute
Authority:
United States: Federal Government
Study ID:
CDR0000068117
NCT ID:
NCT00006106
Start Date:
July 1999
Completion Date:
Related Keywords:
- Lip and Oral Cavity Cancer
- Head and Neck Cancer
- Oropharyngeal Cancer
- 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
- Neoplasms, Squamous Cell
- Head and Neck Neoplasms
- Mouth Neoplasms
- Oropharyngeal Neoplasms
- Lip Neoplasms
Name | Location |
|---|---|
| Massachusetts General Hospital Cancer Center | Boston, Massachusetts 02114 |
| Dana-Farber Cancer Institute | Boston, Massachusetts 02115 |
