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

NCT ID: NCT00272181

Last Updated: 2015-12-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

15 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-01-31

Study Completion Date

2007-10-31

Brief Summary

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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

Detailed Description

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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.

Conditions

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Squamous Cell Carcinoma of the Head and Neck Carcinoma, Squamous Cell Neoplasms, Squamous Cell Head and Neck Neoplasms Mouth Neoplasms Head and Neck Cancer

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Proxinium

Intervention Type DRUG

Intratumoral administration of Proxinium directly to target tumors.

Interventions

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Proxinium

Intratumoral administration of Proxinium directly to target tumors.

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sesen Bio, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Wendy Cuthbert

Role: STUDY_DIRECTOR

Sesen Bio, Inc.

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

UCLA Medical Center

Los Angeles, California, United States

Site Status

John P. Thropay, MD

Montebello, California, United States

Site Status

Mile High Oncology

Denver, Colorado, United States

Site Status

M.D. Anderson Cancer Center Orlando

Orlando, Florida, United States

Site Status

Evanston Northwestern Healthcare

Evanston, Illinois, United States

Site Status

Ingalls Memorial Hospital

Harvey, Illinois, United States

Site Status

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

LSU Health Sciences Center

Shreveport, Louisiana, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

Portland VA Medical Center

Portland, Oregon, United States

Site Status

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Mary Crowley Medical Research Center

Dallas, Texas, United States

Site Status

Princess Margaret Hospital

Toronto, Ontario, Canada

Site Status

CHUQ, L'Hotel-Dieu de Quebec

Québec, Quebec, Canada

Site Status

Countries

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United States Canada

Other Identifiers

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VB4-845-01-IIA

Identifier Type: -

Identifier Source: org_study_id

NCT00335842

Identifier Type: -

Identifier Source: nct_alias