Dendritic Cell Based Therapy for Breast Cancer Patients

NCT ID: NCT00935558

Last Updated: 2012-05-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE2

Study Classification

INTERVENTIONAL

Study Start Date

2009-07-31

Brief Summary

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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

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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).

Conditions

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Breast Cancer

Keywords

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dendritic cell cancer vaccine breast cancer aromatase inhibitor Zadaxin

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Aromatase inhibitor and DC vaccination

the HLA-A2 positive patients will be treated with AI, DC vaccines, Zadaxin and IL-2

Group Type EXPERIMENTAL

DC vaccine

Intervention Type BIOLOGICAL

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

Aromatase inhibitor

the HLA-A2 negative patients will receive AI only

Group Type ACTIVE_COMPARATOR

DC vaccine

Intervention Type BIOLOGICAL

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

aromatase inhibitor

Intervention Type DRUG

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

Interventions

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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

Intervention Type BIOLOGICAL

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

Intervention Type DRUG

Other Intervention Names

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dendritic cell vaccine Thymosin 1 alpha, Zadaxin®, Sigma-Tau Interleukin-2, Proleukin®, Chiron B.V. Aromatase inhibitor:Exemestane, (Aromasin®), Pfizer or Femar®,letrozol, Novartis Healthcare or Arimidex®, anastrozol, AstraZeneca Aromasin®, exemestane, Pfizer Femar®, letrozol, Novartis Healthcare Arimidex, anastrozol, AstraZeneca

Eligibility Criteria

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Inclusion Criteria

* Patients with histological proven metastatic or locally advanced ER+/PGR+ breast cancer in progression after receiving 1. line endocrine therapy.

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
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Inge Marie Svane

OTHER

Sponsor Role lead

Responsible Party

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Inge Marie Svane

Prof, MD, PhD

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Inge Marie Svane, prof MD

Role: STUDY_DIRECTOR

Department of Oncology, Copenhagen University Hospital, Herlev, Herlev Ringvej 75, DK-2730 Herlev; Denmark

Locations

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Department of Oncology, Copenhagen University Hospital, Herlev

Herlev, , Denmark

Site Status

Countries

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Denmark

References

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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.

Reference Type BACKGROUND
PMID: 17285289 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 14985857 (View on PubMed)

Other Identifiers

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MA 0822

Identifier Type: -

Identifier Source: org_study_id