Dendritic Cell Based Therapy for Breast Cancer Patients

Breast Cancer Clinical Trial

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.

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00935558
• Other study ID #: MA 0822
• Status: Withdrawn
• Phase: Phase 2
• First received: July 8, 2009
• Last updated: May 30, 2012
• Start date: July 2009

Study information

• Verified date: May 2012
• Source: Herlev Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Medicines Agency
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. primary completion date: May 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Biological:
• DC vaccine
DC vaccination regime consist of primary 10 intradermal injections of 1-2 weeks interval. At the time of each vaccine 6 MIU/m² IL-2 will be administered sc. Zadaxin 1.6 mg is injected sc twice a week. and tablet Aromatase inhibitor is administered ; Exemestane 25 mg (tablet) is administered PO daily or Femar 2,5 mg (tablet) is administered PO daily or Arimidex 1 mg (tablet) is administered PO daily

Drug:
• aromatase inhibitor
Exemestane 25 mg (tablet) is administered PO daily or Femar 2,5 mg (tablet) is administered PO daily or Arimidex 1 mg (tablet) is administered PO daily

Locations

Country	Name	City	State
Denmark	Department of Oncology, Copenhagen University Hospital, Herlev	Herlev

Sponsors (1)

Lead Sponsor	Collaborator
Inge Marie Svane

Country where clinical trial is conducted

Denmark, 

References & Publications (2)

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. Epub 2007 Feb 7. — View 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. Epub 2004 Feb 25. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine time to progression		after 8 and 16 weeks	No
Secondary	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	Yes