Clinical trial NCT00935558: Dendritic Cell Based Therapy for Breast Cancer Patients
Official title: Evaluation of p53peptide-pulsed Dendritic Cells in Combination With an Aromatase Inhibitor as a Treatment for Patients With Breast Cancer With Disease Recurrence After Adjuvant or First Line Endocrine Therapy.
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Breast Cancer
Keywords: dendritic cell
cancer vaccine
breast cancer
aromatase inhibitor
Zadaxin
Lead sponsor: Herlev Hospital
Sponsor class: OTHER
First posted: 2009-07-09
Enrollment: 0
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary aim of this study is to investigate time to progression in breast cancer patients vaccinated with autologous dendritic cells pulsed with peptides in combination with adjuvant aromatase inhibitor (AI), Thymosin 1 alpha and interleukin-2. The secondary aim is to investigate whether a measurable immune response can be induced, and to evaluate the clinical effect (objective response rate) of the vaccination regime.

Detailed description: Only patients who have tumors \> 5 % positive for p53 by IHC can be referred to this treatment. All patients will receive standard dosage of AI +/- p53-DC vaccination. Patients who express HLA-A2 will also receive DC vaccination. Patients that do not express HLA-A2 will receive only AI and be regarded as controls.

The vaccination regime consists of primary 10 intradermal injections of 1-2 weeks interval (q1w x 4 → q2w x 6) with p53 peptide-pulsed dendritic cells, followed by monthly injections until progression; proleukin and Zadaxin are used as vaccine adjuvants.

Defined procedures are employed for generation of autologous dendritic cells for clinical application in a classified laboratory. Unmobilized leukapheresis will be used for isolation of large-scale mononuclear cells, and dendritic cells will be generated from monocytes by cytokine stimulation and loaded with p53 peptides. Frozen preparations of dendritic cells will be prepared using automated cryopreservation.Each patient will receive a minimum of 5x10\^6 dendritic cells per treatment supplemented with interleukin-2 6 MIU/m² sc per vaccine and 1.6 mg Thymosin 1 alpha sc x 2/week.

Toxicity including autoimmunity will be evaluated using the common Toxicity Criteria (CTC).

Eligibility criteria: Inclusion Criteria:

* Patients with histological proven metastatic or locally advanced ER+/PGR+ breast cancer in progression after receiving 1. line endocrine therapy.
* Further inclusion criteria: p53+ tumour, PS≤1, postmenopausal. Age \>18, PS ≤ 1 and acceptable CBC and blood chemistry results

Exclusion Criteria:

* Patients with a history of any other neoplastic disease less than 5 years ago (excepting treated carcinoma in situ of the cervix and basal/squamous carcinoma of the skin)
* Patients with metastatic disease in the central nervous system
* Patients with other significant illness including severe allergy, asthma, DM, angina pectoris or congestive heart failure
* Patients with acute or chronic infection including HIV, hepatitis og TB
* Patients who received antineoplastic therapy including chemotherapy, radiation, immunotherapy or other agents, less than 4 weeks before the beginning of the trial
* Patients who received corticosteroids or other immunosuppressive agents
* Patients with active autoimmune diseases such as lupus erythematosus, rheumatoid arthritis or thyroiditis
* Severe hypercalcemia

Primary outcomes:
measure: To determine time to progression
timeFrame: after 8 and 16 weeks
Secondary outcomes:
measure: To evaluate safety of DC vaccination in combination with AI, to evaluate clinical tumor response, to evaluate treatment induced immune response to p53 end to evaluate duration of tumor and immune responses
timeFrame: Weekly the first 4 weeks, thereafter biweekly for five months, thereafter monthly
Other outcomes:
Locations:
city: Herlev
country: Denmark
facility: Department of Oncology, Copenhagen University Hospital, Herlev
Study officials:
affiliation: Department of Oncology, Copenhagen University Hospital, Herlev, Herlev Ringvej 75, DK-2730 Herlev; Denmark
name: Inge Marie Svane, prof MD
role: STUDY_DIRECTOR
References:
citation: Svane IM, Pedersen AE, Johansen JS, Johnsen HE, Nielsen D, Kamby C, Ottesen S, Balslev E, Gaarsdal E, Nikolajsen K, Claesson MH. Vaccination with p53 peptide-pulsed dendritic cells is associated with disease stabilization in patients with p53 expressing advanced breast cancer; monitoring of serum YKL-40 and IL-6 as response biomarkers. Cancer Immunol Immunother. 2007 Sep;56(9):1485-99. doi: 10.1007/s00262-007-0293-4. Epub 2007 Feb 7.
citation: Svane IM, Pedersen AE, Johnsen HE, Nielsen D, Kamby C, Gaarsdal E, Nikolajsen K, Buus S, Claesson MH. Vaccination with p53-peptide-pulsed dendritic cells, of patients with advanced breast cancer: report from a phase I study. Cancer Immunol Immunother. 2004 Jul;53(7):633-41. doi: 10.1007/s00262-003-0493-5. Epub 2004 Feb 25.