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Allogenic Immunotherapy Based on Natural Killer (NK) Cell Adoptive Transfer in Metastatic Gastrointestinal Carcinoma Treated With Cetuximab

NCT02845999 · Status: COMPLETED · Phase: PHASE1 · Type: INTERVENTIONAL · Enrollment: 9

Last updated 2016-07-27

No results posted yet for this study

Summary

Gastrointestinal (GI) cancers account for the most common cancers. Despite recent advances in GI cancer treatments, the 5-year overall survival rate for these patients remain unacceptable, except for patients who are candidates for metastasis surgical resection. Strategies leading to a decrease of metastatic number and size will contribute to improve the probability to undergo a curative surgical procedure.

Haploidentical Natural Killer (NK) cells can persist and expand in vivo following adoptive transfer and may have a role in the treatment of selected malignancies, since the failure to recognize the appropriate KIR ligand on a mismatched tumor cell can trigger NK cell elimination of that target cell. NK also express an activating Fc receptor that mediates antibody-dependent cellular cytotoxicity (ADCC) and production of immune modulatory cytokines in response to antibody-coated targets. Cetuximab, an IgG1 chimeric monoclonal antibody against colorectal cancers that expressed EGFR (epidermal growth factor receptor), improves overall survival and progression-free survival and preserves quality-of-life measures in patients with colorectal cancer in whom other treatments have failed.

In an attempt to improve the outcome in GI cancers, we will conduct a phase I/II clinical trial assessing NK cell based immunotherapy. Patients with liver metastases related to a EGFR+ GI cancer, previously treated by a standard chemotherapy that did not achieve a complete response or a curative resection of residual metastases will be included in this phase I/II trial supported by the French National Institute of Cancer (INCA, PHRC 2005). This phase I/II study will involve 22 patients. The main objective of this study will be to demonstrate the safety of NK hepatic intraarterial infusion in association with cetuximab. Secondary objectives will include the assessment of the clinical efficacity of this strategy.

Conditions

  • Gastrointestinal Metastatic Cancer

Interventions

BIOLOGICAL

allogenic immunotherapy based on Natural Killer cells adoptive transfer

day -1 : donor NK cell purification ; day 0 : adoptive transfer (according to a dose escalation) ; Dose escalation protocol : 3.10\^6 ; 8.10\^6 and 12.10\^6 cells/kg of recipient body weight

BIOLOGICAL

cetuximab

day -8 : cetuximab 400 mg/m2 ; day -1 and every week (for 7 weeks) : cetuximab 250 mg/m2

DRUG

Cyclophosphamide

day -6 : cyclophosphamide 60 mg/Kg

DRUG

fludarabine

day -6 to day -2 : fludarabine 25 mg/m2

DRUG

interleukin-2

day -1 : addition of 1000 UI/ml of interleukin 2 to NK cells and overnight culture at 37°C, 5%CO2 ; day 0, hour +12 : 10 MUI of interleukin 2 injection, 2 times a week during 3 weeks.

Sponsors & Collaborators

  • National Cancer Institute, France

    collaborator OTHER_GOV

  • Centre Hospitalier Universitaire de Besancon

    lead OTHER

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Max Age
65 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2009-11-30
Primary Completion
2013-01-31

Countries

  • France

Study Locations

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Entities

Drugs

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT02845999 on ClinicalTrials.gov