- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02285413
Platin-based Chemotherapeutics to Enhance Dendritic Cell Vaccine Efficacy in Melanoma Patients
Immunochemotherapy: Do Platin-based Chemotherapeutics Enhance Dendritic Cell Vaccine Efficacy in Melanoma Patients?
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Rationale Investigators have explored immunotherapy and have now vaccinated well over 200 stage III and IV melanoma patients in the Netherlands with monocyte-derived dendritic cell (DC) vaccines and proved that DC therapy is safe with minimal side effects.
Cytotoxic chemotherapy and radiotherapy have long been viewed as strategies that directly impact the viability of the tumor cell, and that the immune system contributed little to their efficacy. The commonly held opinion was that chemotherapy and immunotherapy could not be combined because of the myelo-suppressive effect of most chemotherapeutic agents. However, it becomes increasingly obvious that chemotherapy also possess the capacity to trigger tumor antigen release and danger signals in a manner that provokes engagement of innate and adaptive immunity that may be capitalized upon.
Small proof-of-concept clinical trials in cancer patients indicate that the efficacy of anti-cancer vaccines may indeed be enhanced by chemotherapy [2]. Also preliminary observations indicate that chemotherapeutic agents, in particular platinum compounds (cisplatin, carboplatin and oxaliplatin) are immunogenic and may contribute to reverse tumor cell induced immunosuppression/immune deviation.
Investigators hypothesize that DC vaccination, when combined with other more conventional anti-tumor treatments such as chemotherapy, that eradicate large numbers of cancer cells, may allow the T cells to clear the remaining cancer cells and to provide immunological memory to prevent relapse.
- Objectives This is an exploratory study and the primary objective is the immunogenicity and feasibility of combined chemotherapy-DC vaccination. The secondary objectives are the toxicity and clinical efficacy. This study will provide important data on the immunological efficacy of DC immunochemotherapy.
- Study design This study is an open label randomized phase II study.
- Study population Our study population consists of melanoma patients, with expression of melanoma associated tumor antigens gp100 and tyrosinase. Melanoma patients with regional lymph node metastasis in whom a radical lymph node dissection is performed within 2 months of inclusion in this study (further referred to as stage III) and melanoma patients with measurable distant metastases (further referred to as stage IV) will be included.
- Main study endpoints The primary objective of the study is to investigate the immunogenicity and feasibility of combined chemotherapy-DC vaccination. The secondary objective is to investigate the toxicity and clinical responses (only in stage IV) upon DC immunochemotherapy.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Gelderland
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Nijmegen, Gelderland, Netherlands, 6500 HB
- Radboud University Nijmegen Medical Centre
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
All patients:
- histologically documented evidence of melanoma
- stage III or IV melanoma according to the 2001 AJCC criteria
- melanoma expressing gp100. Tyrosinase is not mandatory but will be assessed.
- WHO performance status 0-1 (Karnofsky 100-70)
- life expectancy ≥3 months
- age 18-70 years
- no clinical signs or symptoms of CNS metastases
- WBC >3x10^9/l, lymphocytes >0.8x10^9/l, platelets >100x10^9/l, serum creatinine <150 µmol/l, serum bilirubin <25 µmol/l
- normal serum LDH (<450 U/l)
- expected adequacy of follow-up
- no pregnant or lactating women
- written informed consent
and in addition: Stage III melanoma
- radical regional lymphnode dissection is performed Stage IV melanoma
- at least one unidimensional measurable target lesions according to RECIST, not previously irradiated, and no significant symptoms of disease requiring other palliative treatments
Exclusion Criteria:
- any prior chemotherapy, immunotherapy or radiotherapy is allowed if completed more than 4 weeks prior to planned vaccination
- history of any second malignancy in the previous 5 years, with the exception of adequately treated basal cell carcinoma or carcinoma in situ of the cervix
- serious active infections, known HbsAg or HIV positive, or autoimmune diseases or organ allografts
- concomitant use of immunosuppressive drugs
- known allergy to shell fish (since it contains KLH)
- rapidly progressive symptomatic disease
- any serious clinical condition that may interfere with the safe administration of DC
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: DC vaccination
mature DC injected intradermally and intravenously loaded with mRNA encoding tumor-associated antigens gp100 and tyrosinase
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DC vaccination without cisplatinum
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Experimental: DC vaccination with cisplatinum
mature DC injected intradermally and intravenously loaded with mRNA encoding tumor-associated antigens gp100 and tyrosinase.
each DC vaccine will be preceded by cisplatin infusion: 50 mg/m2, 1-2h before DC injection.
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DC vaccination with cisplatinum
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Immunogenicity: number of participants with KLH and/or tumor-specific antigens immune responses.
Time Frame: 5 years
|
5 years
|
Feasibility: % of vaccines meeting the release criteria.
Time Frame: 5 years
|
5 years
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Overall survival
Time Frame: 5 years
|
5 years
|
Progression-free survival
Time Frame: 5 years
|
5 years
|
Toxicity: number of Participants with Adverse Events.
Time Frame: 5 years
|
5 years
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Best objective response (only in stage IV)
Time Frame: 5 years
|
5 years
|
Collaborators and Investigators
Investigators
- Principal Investigator: Winette van der Graaf, professor, Radboud university medical center
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- NL32381.000.10
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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