Safety and Efficacy Study of DCVax-Direct in Solid Tumors

Study Overview
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Brief Summary
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The study comprises a Phase I component during which the optimal dose of DCVax-Direct for the treatment of solid tissue tumors will be identified, followed by a Phase II component to determine if the injection of DCVax-Direct into selected solid tissue tumors has the ability to reduce tumor growth.

Official Title
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A PHASE I/II CLINICAL TRIAL EVALUATING DCVax-Direct, AUTOLOGOUS ACTIVATED DENDRITIC CELLS FOR INTRATUMORAL INJECTION, IN PATIENTS WITH SOLID TUMORS

Conditions
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Locally Advanced Tumor, Metastatic Solid Tissue Tumors, Liver Cancer, Colorectal Cancer, Pancreatic Cancer, Melanoma

Intervention / Treatment
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* Biological: DCVax-Direct


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (summary): Age between 18 and 75 years (inclusive) at screening. Karnofsky performance status (KPS) of 70 or higher or Eastern Cooperative Oncology Group (ECOG) 0-1 at screening. Subjects with a histological or cytopathological confirmed diagnosis of a locally advanced or metastatic solid tumor malignancy for which primary treatment is no longer effective or does not offer curative or life-prolonging potential per clinician judgment, with the understanding that DCVax-Direct is not intended as a treatment of last resort. Not eligible for complete resection due to either tumor location, physician's assessment or subject's choice. Must have completed at least one recent treatment regimen in the metastatic or advanced setting in the disease currently under treatment to reduce tumor burden. Any steroid therapy >2 mg dexamethasone or equivalent dose should be stopped or have been tapered down 2 weeks prior to the leukapheresis. At least one measurable tumor mass, i.e. a lesion that can accurately be measured by CT/MRI in at least one dimension with longest diameter ≥ 1 cm, that is accessible for injection either with or without imaging (CT/ultrasound) guidance. Adequate hematological, hepatic, and renal function, Adequate blood coagulation parameters Life expectation of >3 months. Exclusion Criteria (Summary): Positive HIV-1, HIV-2, or Human T-lymphotropic virus (HTLV-I/II) tests. History of current or prior (within the last two years) active clinically significant malignancy other than the tumor type for which DCVax-Direct treatment is considered, and except for primary tumor in the case of metastases and adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer. Heavily pretreated (HP) subjects are not eligible for this study, unless treatments have occurred more than 1 year in the past. Presence of brain metastases, unless treated surgically and/or irradiated and clinically stable off steroids or on low dose (< 2 mg per day) steroids for ≥ 14 days, or presence of leptomeningeal disease. History of immunodeficiency or unresolved autoimmune disease. Requirement for ongoing immunosuppressants. Prior active immunotherapy for cancer within the past 2 years. Ongoing medical need for continuous anti-coagulation or anti-platelet medication. Known genetic cancer-susceptibility syndromes. Acute or active uncontrolled infection Ongoing fever ≥ 101.5 degrees F/38.6 degrees C at screening. Unstable or severe intercurrent medical conditions such as unstable angina, uncontrolled arrhythmias, Crohn's Disease, ulcerative colitis etc. Females of child-bearing potential who are pregnant or lactating or who are not using adequate contraception (surgical, hormonal or double barrier, i.e. condom and diaphragm). Allergy or anaphylaxis to any of the reagents used in this study. Inability to obtain informed consent because of psychiatric or complicating medical problems. Inability or unwillingness to return for required visits and follow-up exams.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DCVax-Direct<br>DCVax-Direct: autologous, activated dendritic cells for intratumoral injection | Biological: DCVax-Direct<br>* Autologous, activated dendritic cells for intratumoral injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with adverse events |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with tumor response |  | 18 months |