NCT02845999

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

Allogenic Immunotherapy Based on Natural Killer Cell Adoptive Transfer in Metastatic Gastrointestinal Carcinoma Treated With Cetuximab : a Phase I Trial

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 9 (actual)
• Sponsor: Centre Hospitalier Universitaire de Besancon · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Patients will be treated with a conditioning chemotherapy including 60 mg/kg intravenous cyclophosphamide, 25 mg/m2 intravenous fludarabine for 5 consecutive days and cetuximab. A lymphapheresis from an haploidentical related donor will be performed and T cells will be depleted . Allogenic NK cells will then be adoptively transferred by hepatic intraarterial infusion according to a dose escalation protocol (three doses with at least three patients per cohort)to define the dose-limiting toxicity (DLT). Then 10 more patients will receive the recommended NK cell dose. Dose escalation protocol : 3.10\^6 ; 8.10\^6 and 12.10\^6 cells/kg of recipient body weight.

Conditions

• Gastrointestinal Metastatic Cancer

Interventions

Type	Name	Description
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.

Timeline

• Start date: 2009-11-01
• Primary completion: 2013-01-01
• First posted: 2016-07-27
• Last updated: 2016-07-27

Locations

1 site across 1 country: France