Immunotherapy of Advanced Cancer Using a Combination Nimotuzumab and NK Cells

A Phase I Trial of Combined Nimotuzumab With NK Cells Adoptive Transfer for the Treatment of Advanced Cancer

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.

Study Overview

• Status: Unknown
• Conditions: Advanced Cancer; ADCC; NK Cell Mediated Immunity; Nimotuzumab; Adaptive Transfer
• Intervention / Treatment: Biological: NK Cell adaptive transfer; Drug: Nimotuzumab

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 Type: Interventional
• Enrollment (Anticipated): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310002
      • Hangzhou Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Experimental Group; 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.

Biological: NK Cell adaptive transfer; Nimotuzumab will enhance the ADCC effect of NK Cell adaptive transfer; Drug: Nimotuzumab; Nimotuzumab will enhance the ADCC effect of NK Cell adaptive transfer

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events	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	6 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate	Response will be evaluated according to RECIST v1.1	3 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS)	From date of randomization until the date of first documented progression or date of death from any cause	1 year
Overall Survival (OS)	The time from randomization to death from any cause	1 year
Peripheral blood circulating tumor DNA	Peripheral circuiting tumor DNA is collected at baseline and 6 weeks after last treatment	6 weeks

Collaborators and Investigators

• Sponsor: Hangzhou Cancer Hospital
• Collaborators: Shanghai bokang bioengineering co., LTD
• Investigators: Principal Investigator: Shixiu Wu, Doctor, Hangzhou Cancer Hospital

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): August 1, 2018
• Primary Completion (ANTICIPATED): March 30, 2019
• Study Completion (ANTICIPATED): November 27, 2019

Study Registration Dates

• First Submitted: May 24, 2018
• First Submitted That Met QC Criteria: June 12, 2018
• First Posted (ACTUAL): June 13, 2018

Study Record Updates

• Last Update Posted (ACTUAL): June 13, 2018
• Last Update Submitted That Met QC Criteria: June 12, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Nimotuzumab
• Other Study ID Numbers: HangzhouCH11

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No