Dendritic Cell Based Therapy for Breast Cancer Patients

Phase 2

Withdrawn

• Conditions: Breast Cancer
• Interventions: Biological: DC vaccine; Drug: aromatase inhibitor

• Registration Number: NCT00935558
• Lead Sponsor: Inge Marie Svane

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).

Study Timeline

• Study Start: 2009-07
• Study First Submitted: 2009-07-08
• Study First Submitted QC: 2009-07-08
• Study First Posted: 2009-07-09
• Status Verified: 2012-05
• Primary Completion: 2012-05
• Last Update Submitted: 2012-05-30
• Last Update Posted: 2012-05-31

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: Female
• Target Recruitment: Not specified

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Aromatase inhibitor and DC vaccination	DC vaccine	the HLA-A2 positive patients will be treated with AI, DC vaccines, Zadaxin and IL-2
Aromatase inhibitor	DC vaccine	the HLA-A2 negative patients will receive AI only
Aromatase inhibitor	aromatase inhibitor	the HLA-A2 negative patients will receive AI only

Primary Outcome Measures

Name	Time	Method
To determine time to progression	after 8 and 16 weeks

Secondary Outcome Measures

Name	Time	Method
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	Weekly the first 4 weeks, thereafter biweekly for five months, thereafter monthly

Trial Locations

Locations (1)

Department of Oncology, Copenhagen University Hospital, Herlev; 🇩🇰 Herlev, Denmark