A Phase I Study Of PV701 In Patients With Head And Neck Squamous Cell Carcinoma
Trial Snapshot
- Phase
- Phase 1
- Status
- Terminated
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Maximum-tolerated dose (MTD) of PV701 based on the incidence of dose-limiting toxicity (DLT) as assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
Study Overview
Brief Summary
Phase I trial to study the effectiveness of intratumoral (in the tumor) PV701 in treating patients who have advanced or recurrent unresectable squamous cell carcinoma (cancer) of the head and neck. Vaccines made from a specially-modified virus such as PV701 may make the body build an immune response to kill tumor cells while leaving normal cells undamaged. Injecting PV701 directly into the tumor may cause a stronger immune response and kill more tumor cells
Detailed Description
OBJECTIVES:
I. Determine the maximum tolerated dose (MTD) of PV701 administered by direct intratumoral injection in patients with advanced or recurrent unresectable squamous cell carcinoma of the head and neck.
II. Determine the toxicity of intratumoral PV701 in these patients. III. Determine response rate and time to progression at the injection site in patients treated with this drug.
OUTLINE: This is a dose-escalation study. Patients receive intratumoral PV701 once weekly for 3 weeks. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of PV701 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, at least 6 evaluable patients are treated at that dose.
PROJECTED ACCRUAL: A maximum of 30 patients will be accrued for this study within 6-10 months.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Histologically or cytologically confirmed squamous cell carcinoma of the head and neck
- •Locally advanced or recurrent disease
- •Distant metastases in addition to locally advanced disease acceptable
- •Not amenable to available standard treatment or palliative measures
- •At least one target lesion accessible for intratumoral injection, less than 4 cm, and not situated near an airway or major artery
- •Tumor volume(s) must be large enough to receive injection
- •No known brain metastases
- •Performance status - ECOG 0-2
- •More than 3 months
- •WBC >= 3,000/mm^3
- •Hemoglobin > 10 g/dL (transfusion permitted)
- •Platelet count >= 100,000/mm^3
- •Bilirubin < 2 times upper limit of normal (ULN)
- •AST/ALT =< 2.5 times ULN
- •Creatinine < 2.5 mg/dL
- •No uncontrolled symptomatic congestive heart failure
- •No unstable angina pectoris
- •No cardiac arrhythmia
- •No history of significantly compromised pulmonary function (i.e. FEV_1 < 50% of predicted) or decreased oxygen saturation of < 95% on room air
- •No history of allergy to eggs or egg-based or chicken embryo-based vaccines
- •No frequent contact with immunocompromised individuals
- •No ongoing or active infection
- •No psychiatric illness or social situation that would preclude study compliance
- •No history of diabetes mellitus requiring oral hypoglycemic agents or insulin
- •No HIV-positive patients receiving combination antiretroviral therapy
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •More than 4 weeks since prior chemotherapy and recovered
- •More than 4 weeks since prior radiotherapy and recovered
- •More than 4 weeks since prior surgery and recovered
- •No other concurrent investigational agents or commercial agents or therapies for treatment of malignancy
- •No concurrent antiviral therapy
Exclusion Criteria
- Not provided
Arms & Interventions
Treatment (PV701)
Patients receive intratumoral PV701 once weekly for 3 weeks. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of PV701 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, at least 6 evaluable patients are treated at that dose.
Intervention: PV701 (Biological)
Outcomes
Primary Outcomes
Maximum-tolerated dose (MTD) of PV701 based on the incidence of dose-limiting toxicity (DLT) as assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
Time Frame: 3 weeks
Secondary Outcomes
- Toxicity as assessed by NCI CTCAE version 3.0(Up to 12 weeks)
- Response (complete and partial) rate according to Response Evaluation Criteria in Solid Tumors (RECIST) Committee(Up to 12 weeks)
- Time to progression according to RECIST(From the time of study entry until tumor growth is determined by physical exam or by radiographic imaging, assessed up to 12 weeks)