Study of Proxinium for Treating Patients With Squamous Cell Head and Neck Cancer

Sponsor

Viventia Bio (Industry)

Overall Status

Terminated

CT.gov ID

NCT00272181

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

0.8

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the safety, effectiveness, and recommended dose of Proxinium in North American patients with Squamous Cell Head and Neck Cancer

Condition or Disease	Intervention/Treatment	Phase
Squamous Cell Carcinoma of the Head and Neck Carcinoma, Squamous Cell Neoplasms, Squamous Cell Head and Neck Neoplasms Mouth Neoplasms Head and Neck Cancer	Drug: Proxinium	Phase 2

Detailed Description

This study was an open-label, multicentre, dose determination study evaluating the safety and tolerability of Proxinium in the treatment of patients with advanced SCCHN who had received at least one anti-cancer treatment regimen for advanced disease. Fifteen patients were enrolled at nine sites. All patients with histologically confirmed SCCHN who had advanced disease were considered potential candidates for study entry.

Patients completed two phases of screening termed Initial Screening and Final Screening. Initial Screening assessed the EpCAM status of the patient's SCCHN prior to final screening procedures taking place. Patients had to have a biopsy of their advanced disease that had been appropriately collected for verification of EpCAM-positive SCCHN by immunohistochemical methods. If EpCAM-positive SCCHN was confirmed, the patient could enter Final Screening to determine full eligibility for participation in the study. At the beginning of Final Screening, all patients had to have received at least one anti-cancer treatment regimen for advanced disease. Patients who had successfully completed both Initial and Final Screening had a Principal Target Tumour and up to five additional Target Tumours designated for treatment prior to Day 1 dosing. Only one target tumour per week was to be injected. The Investigator was to treat the principal target tumour until clinically relevant tumour control of the principal target tumour was achieved, at which point other target tumours could be chosen and injected once per week at the same dose level of Proxinium.

The study was to comprise two stages. In Stage I, the recommended dose (RD) for Proxinium was to be determined based on the rate of dose-limiting toxicities (DLTs) within each dose cohort. A DLT was defined as the occurrence of excessive toxicity during the first four weeks of each patient's treatment with Proxinium during Stage I of the study, before the RD had been determined. The RD was to be established as the highest dose at which one or fewer patients out of six within a dose cohort experienced a DLT. The initial dose level was to be 500 µg, and three patients were to be initially enrolled into this dose cohort.

Doses were to be escalated to a maximum of 700 µg or de-escalated to a minimum of 260 µg according to the prescribed algorithm outlined in the study protocol and based on the number of patients experiencing a DLT within each dose cohort. Safety data was to be reviewed by the medical monitor, the site investigators who had enrolled patients at that dose, and Viventia Biotech Inc. (the sponsor) to determine if escalation or de-escalation was to occur. All Stage I patients, including those in the original RD cohort, were to remain in Stage I and continue treatment beyond their initial four weeks at their original dose assignment. If dose de-escalation was deemed necessary, all Investigators with patients receiving higher doses would have been notified and given the option of either administering a de-escalated dose or discontinuing treatment.

Stage II was to commence once the RD had been determined and an independent third party had reviewed the safety data. Patients enrolled subsequently were to receive treatment at the RD.

The RD cohort was to be expanded to include a total of 15 patients, and safety and efficacy evaluation was to continue being assessed.

Continued safety and tolerability as well as response rates, therapeutic endpoints, survival time, PK parameters, and immunogenicity were evaluated. Regardless of dose cohort, all patients were to be treated until complete resolution of all accessible Target Tumours, clinically relevant tumour progression, or until study drug suspension or withdrawal criteria had been met.

Four weeks after the end-of-treatment visit, patients were to return to the site for a follow-up visit that was to include a CT scan of the head and neck as well as other assessments, as described in the study protocol. Subsequently, patients were to enter the post-study surveillance period.

Enrolment in the study was halted before the RD of Proxinium was determined, and hence, Stage II of this study was not conducted.

Study Design

Study Type:

Interventional

Actual Enrollment :

15 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II, Open-Label Study to Evaluate the Safety, Tolerability, and Pharmacokinetic Profile of Proxinium in Patients With Advanced SCCHN Who Have Received at Least One Anti-Cancer Treatment Regimen for Advanced Disease

Study Start Date :

Jan 1, 2006

Actual Primary Completion Date :

Oct 1, 2007

Actual Study Completion Date :

Oct 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose Determination The recommended dose (RD) for Proxinium is to be determined based on the rate of Dose Limiting Toxicities (DLT) within each dose cohort. The RD is to be established as the highest dose at which one or fewer patients out of six within a dose cohort experienced a DLT. The initial dose level is 500 μg of Proxinium in PBS (the amount of PBS used will be based on the estimated volume of the target tumour). Doses are to be escalated to a maximum of 700 μg or de-escalated to a minimum of 260 μg according to the prescribed algorithm outlined in the study protocol.	Drug: Proxinium Intratumoral administration of Proxinium directly to target tumors.

Arm

Intervention/Treatment

Experimental: Dose Determination

The recommended dose (RD) for Proxinium is to be determined based on the rate of Dose Limiting Toxicities (DLT) within each dose cohort. The RD is to be established as the highest dose at which one or fewer patients out of six within a dose cohort experienced a DLT. The initial dose level is 500 μg of Proxinium in PBS (the amount of PBS used will be based on the estimated volume of the target tumour). Doses are to be escalated to a maximum of 700 μg or de-escalated to a minimum of 260 μg according to the prescribed algorithm outlined in the study protocol.

Drug: Proxinium

Intratumoral administration of Proxinium directly to target tumors.

Outcome Measures

Primary Outcome Measures

To determine the safety, tolerability and recommended dose (RD) of Proxinium [Weekly dosing]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Disease Characteristics:

Histologically confirmed recurrent squamous cell carcinoma of the head and neck.
Immunohistochemically confirmed epithelial cell adhesion molecule (EpCAM)-positive SCCHN.
Must have at least 1 accessible target tumor that is amenable to adequate direct injection.
The patient must have at least 1 accessible target tumor without direct carotid artery involvement.

Prior/Concurrent Therapy:

The patient must have received therapy for their primary disease
The patient must have been diagnosed with persistent or recurrent disease or a second primary tumour.
The patient's disease must be refractory.
There must be at least 2 weeks between the last dose of chemotherapy or radiotherapy and receiving study drug or 4 weeks between the last dose of an experimental drug and receiving study drug.

Patient Characteristics:

Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
Life expectancy of at least 12 weeks.
Adequate hepatic function ALT and AST and total bilirubin levels ≤1.5 times ULN.
Adequate renal function (serum creatinine <2.0 mg/dL).
Hematologic values consisting of granulocytes ≥1500/μL, platelets ≥100 000/μL, and hemoglobin >8 g/dL.
Prothrombin time and partial thromboplastin time within normal limits

Other:

The patient must provide written informed consent.
Fertile patients must use effective contraception

Exclusion Criteria:

Brain tumor or brain metastases.
Nasopharyngeal SCCHN.
Human immunodeficiency virus, hepatitis C virus, or hepatitis B surface antigen.
Uncontrolled bleeding from any target tumor(s) that are being considered for treatment or a history of tumor hemorrhage that has required medical intervention (other than direct compression).
The patient is a candidate for surgical tumor resection of their target tumor(s).
Pregnant or lactating.
Clinically significant renal or hepatic disease.
Requires regular use of aspirin, full-dose warfarin, or heparin.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294-3300
2	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
3	UCLA Medical Center	Los Angeles	California	United States	90095
4	John P. Thropay, MD	Montebello	California	United States	90640
5	Mile High Oncology	Denver	Colorado	United States	80210
6	M.D. Anderson Cancer Center Orlando	Orlando	Florida	United States	32806
7	Evanston Northwestern Healthcare	Evanston	Illinois	United States	60201
8	Ingalls Memorial Hospital	Harvey	Illinois	United States	60426
9	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
10	LSU Health Sciences Center	Shreveport	Louisiana	United States	71103
11	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
12	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
13	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73190
14	Portland VA Medical Center	Portland	Oregon	United States	97239
15	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104-4283
16	Medical University of South Carolina	Charleston	South Carolina	United States	29425
17	Mary Crowley Medical Research Center	Dallas	Texas	United States	75201
18	Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
19	CHUQ, L'Hotel-Dieu de Quebec	Quebec City	Quebec	Canada	GIR 5C3