Dendritic Cells for Immunotherapy of Metastatic Endometrial Cancer Patients

NCT04212377 | Completed Phase 2 DMC

• 1 other identifier: NL68332.000.18
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

Prevention of infectious diseases through immunization is one of the greatest achievements of modern medicine. Nonetheless, considerable challenges remain for improving the efficacy of existing vaccines for therapeutic immunizations for diseases such as cancer. The investigators were amongst the first groups worldwide that introduced tumor antigen-loaded dendritic cell (DC)-based vaccines in the clinic1-3. Effective immune responses and favorable clinical outcomes have indeed been observed4-7. Thus far, mainly conventional in vitro generated monocyte-derived DCs (moDC) have been used in clinical trials worldwide. In the past 14 years the investigators have treated more than 375 patients and proven that DC therapy is feasible and non-toxic. The investigators observed that long lasting tumor specific T cell-mediated immunological responses are clearly linked to increased progression free survival as well as overall survival8. In conclusion, based on all these observations the investigators are convinced that pDC and myDC employ different, and probably more optimal mechanisms to combat cancer. In addition, based on in vitro data and preclinical studies that suggest that blood pDC and myDC act synergistically, the investigators hypothesize that the combination of myDC and pDC may induce stronger anti-tumor immune responses as compared to pDC or myDC alone, or moDC.

Conditions

Endometrial Cancer

Keywords

Endometrial Cancer

Outcome Measures

Primary Outcomes (1)

• Immunologic efficacy of tumor-peptide loaded nDC in mEC patients

  Immunomonitoring including: a) functional response and tetramer analysis of DTH infiltrating lymphocytes against tumor peptides

  1 year

Secondary Outcomes (2)

• toxicity: Adverse Events

  study start till week 26

• Health- related Quality of Life

  Baseline, week 15 and week 26

Other Outcomes (1)

• Assessment of T cell responses against tumor peptides

  Baseline, week 8, week 17 and week 24 and week 26

Study Arms (1)

exploratory

EXPERIMENTAL

single arm exploratory, single-centre study

Biological: Dendritic Cells for endometrial cancer

Interventions

Dendritic Cells for endometrial cancer BIOLOGICAL

Our study population consists of 8 mEC patients who receive carboplatin / paclitaxel chemotherapy in a weekly schedule on weeks 1, 2, 3 and weeks 5,6 and 7. In week 8, myeloid and plasmacytoid DC (nDC) are loaded with tumor lysate and MUC1 and survivin PepTivators, injected intranodally. An extensive immuno-motoring will be performed on all patients. Patients who show stable disease, partial response, or full response continue with extended three-week chemotherapy regimens with intranodal injections of nDC at weeks 17, 20, and 23.

exploratory

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: women
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• women ≥ 18 years old with histologically confirmed stage IV or metastatic carcinoma of the endometrium of the endometroid, serous or carcinosarcoma type.
• Hormone receptor negative or
• resistant to hormonal therapy
• ineligible for hormonal therapy because of other reasons
• eligible for treatment with carboplatin paclitaxel combination chemotherapy
• Life expectancy ≥ 6 months
• WHO/ECOG performance status 0-1 (Karnofsky index 100-70)
• WBC \>2.0 -109/l, neutrophils \>1.5-109/L lymphocytes \>0.8-109/L, platelets \>100-109/L, hemoglobin \>5,6 mmol/L (9.0 g/dL), serum creatinine \<150 µmol/L, AST/ALT \<3 x ULN, serum bilirubin \<1.5 x ULN (exception: Gilbert's syndrome is permitted)
• Expression of survivin and/or muc1 on tumor material
• Expected adequacy of follow-up
• Postmenopausal or evidence of non-childbearing status or for women of childbearing potential: negative urine or serum pregnancy test, within 28 days of study treatment and confirmed prior to treatment on day 1
• Postmenopausal is defined as:
• Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments;
• Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in the post menopausal range for women under 50,
• radiation-induced oophorectomy with last menses \>1 year ago,

You may not qualify if:

• Uncontrolled hypercalcemia
• History of any second malignancy in the previous 5 years, with the exception of adequately treated basal cell carcinoma
• Known allergy to shell fish
• Heart failure (NYHA class III/IV)
• Serious active infections
• Active hepatitis B, C or HIV infection
• Active syphilis infection
• Autoimmune diseases (exception: vitiligo is permitted)
• Organ allografts
• An uncontrolled co-morbidity, e.g. psychiatric or social conditions interfering which participation
• Concurrent use of systemic corticosteroids \> 10 mg daily prednisone equivalent
• Any serious clinical condition that may interfere with the safe administration of DC vaccinations
• Unable to undergo a tumor biopsy
• Pregnancy or insufficient anti-conception if reproduction is still possible

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Stichting Katholieke Universiteit: collaborator

Study Sites (1)

Radboud University Medical Center

Nijmegen, 6500 HB, Netherlands

Location

Related Publications (76)

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MeSH Terms

Conditions

Endometrial Neoplasms

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Jolanda de Vries, Prof. Dr.

  Radboud Umiversity Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study is a single arm exploratory, single-centre study

Study Record Dates

• First Submitted: November 20, 2019
• First Posted: December 27, 2019
• Study Start: April 8, 2019
• Primary Completion: March 9, 2021
• Study Completion: March 9, 2021
• Last Updated: January 11, 2024

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)