Immunotherapy of Advanced Cancer Using a Combination Nimotuzumab and NK Cells

Phase 1

• Conditions: NK Cell Mediated Immunity; Advanced Cancer; ADCC; Adaptive Transfer; Nimotuzumab
• Interventions: Biological: NK Cell adaptive transfer; Drug: Nimotuzumab

• Registration Number: NCT03554889
• Lead Sponsor: Hangzhou Cancer Hospital

Brief Summary

NK cells can persist and expand in vivo following adoptive transfer and may have a role in the treatment of late stage malignancies. 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. Nimotuzumab, an monoclonal antibody against EGFR (epidermal growth factor receptor), may enhance the ADCC effect of NK cell. This study will evaluate the safety of combination of nimotuzumab and NK Cell in treating advanced cancer patients. Blood samples will also be collected for research purposes.

Detailed Description

This is a phase I clinical study of expanded NK cells from autologous origin. The NK cell will be selected and expanded ex vivo and infused back into patients. Nimotuzumab will be used 24 hours before infusion. 21 advanced cancer patients are planned to receive two cycles of NK cells and Nimotuzumab treatment. Biomarkers and immunological markers are collected and analyzed as well.

Study Timeline

• Study First Submitted: 2018-05-24
• Status Verified: 2018-06
• Study First Submitted QC: 2018-06-12
• Last Update Submitted: 2018-06-12
• Study First Posted: 2018-06-13
• Last Update Posted: 2018-06-13
• Study Start: 2018-08-01
• Primary Completion: 2019-03-30
• Study Completion: 2019-11-27

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 21

Inclusion Criteria

1. Histologically confirmed recurrent or metastatic cancer
2. Measurable disease
3. Progressed after all standard treatment
4. ECOG performance status of 0 to 2
5. Expected life span ≥ 3 months
6. Toxicities from prior treatment has resolved. Washout period is 4 weeks for chemotherapy, and 2 weeks for targeted therapy
7. Major organs function normally
8. Women at pregnant ages should be under contraception
9. Willing and able to provide informed consent

Exclusion Criteria

1. Other malignancy within 5 years prior to entry into the study, expect for treated non melanoma skin cancer and cervical carcinoma in situ
2. Poor vasculature
3. Disease to the central nervous system
4. Blood-borne infectious disease, eg. hepatitis B
5. History of mandatory custody because of psychosis or other psychological disease inappropriate for treatment deemed by treating physician
6. With other immune diseases, or chronic use of immunosuppressants or steroids
7. Pregnancy (women of childbearing potential: Refusal or inability to use effective means of contraception)
8. Breastfeeding
9. Decision of unsuitableness by principal investigator or physician-in-charge

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Experimental Group	NK Cell adaptive transfer	Peripheral blood lymphocytes will be collected. The NK cell will be selected and expanded ex vivo, then adaptive transfer back into patients. A total of 5.0 x 10\^8/L NK cells will be infused in one cycle.To avoid allergic reactions, 50 mg hydrocortisone was intramuscularly injected into patient 30 min before cells infusion every time. Best supportive care was also provided for patients. Nimotuzumab will be used 24 hours before infusion. Patients continued receiving treatment unless they had unacceptable adverse effects, or progressive disease confirmed by CT and PET-CT or they withdrew consent.
Experimental Group	Nimotuzumab	Peripheral blood lymphocytes will be collected. The NK cell will be selected and expanded ex vivo, then adaptive transfer back into patients. A total of 5.0 x 10\^8/L NK cells will be infused in one cycle.To avoid allergic reactions, 50 mg hydrocortisone was intramuscularly injected into patient 30 min before cells infusion every time. Best supportive care was also provided for patients. Nimotuzumab will be used 24 hours before infusion. Patients continued receiving treatment unless they had unacceptable adverse effects, or progressive disease confirmed by CT and PET-CT or they withdrew consent.

Primary Outcome Measures

Name	Time	Method
Incidence of Treatment-Emergent Adverse Events	6 month	Number of Patients with Clinical or Biological Treatment-related Adverse Events and/or Dose Limiting Toxicities as a Measure of Safety and Tolerability of a Combination of Nimotuzumab and NK Cell as assessed by CTCAE v4.0

Secondary Outcome Measures

Name	Time	Method
Response Rate	3 months	Response will be evaluated according to RECIST v1.1

Trial Locations

Locations (1)

Hangzhou Cancer Hospital; 🇨🇳 Hangzhou, Zhejiang, China