Clinical Study on the Efficacy of Autologous Cell Factor Induced Killer Cells in the Treatment of Colorectal Cancer

Treatment of Colorectal Cancer With Autologous Cytokine Induced Killer Cells (CIK)

This project plans to use CIK combined with chemotherapy, immunotherapy and targeted therapy to treat CRC patients, so as to explore the effectiveness of CIK treatment and the CRC subtypes more suitable for CIK treatment, thereby improving the survival rate and quality of life of CRC patients.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer
• Intervention / Treatment: Combination product: CIK combined with chemotherapy group; Combination product: CIK combined immunotherapy group; Combination product: CIK combined targeted therapy group; Combination product: CIK in combination with other therapies

Detailed Description

Colorectal cancer (CRC) is a malignant tumor that seriously threatens human health, and according to the international agency for research on cancer (IARC) data, in 2018, the number of new cases of CRC totalled more than 1.8 million and the number of deaths totalled more than 88million, making it the third most common cancer worldwide [1]. In recent years, with the development of economic level in China, changes in lifestyle and dietary structure, the incidence and mortality of CRC have shown a continuous increasing trend, and it is ranked 5th in all malignant tumors. According to statistics, at present, our country has 376000 new CRC cases and 191000 deaths annually, and the whole face extremely serious challenges.

Patients with advanced CRC have a more complicated disease, and the 5-year survival rate is even less than 5%. A single therapeutic means cannot achieve the desired therapeutic effect, and often multiple therapeutic modalities are used for intervention, including surgery, radiotherapy, chemotherapy, interventional minimally invasive treatment, immunotherapy and molecular targeting, etc. Because of the potential efficacy of CIK treatment in controlling tumor growth and prolonging patient survival, but there are still few clinical studies about CIK combined with other treatment modalities, this protocol is intended to use CIK combined with chemotherapy, immune and targeted therapy in CRC patients, in order to explore the effectiveness of CIK treatment and more suitable CRC subtypes for CIK treatment, and then improve the survival rate and quality of life of CRC patients.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Chongqing
    • Chongqing, Chongqing, China, 400038
      • Recruiting
      • Southwest Hospital, Army Medical University (Third Military Medical University)
      • Contact: shicang yu, M.D. and Ph.D.; Phone Number: 023-68766452; Email: yushicang@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age range 18-70 years;

  • Patients diagnosed with colorectal cancer, TNM stage III-IV;

    • Had at least one extracranially measurable lesion by recist1.1 criteria; ④ Patients who had failed at least one or two prior lines of standard therapy or relapsed, or who were intolerant to or voluntarily abandoned one or two prior lines of standard therapy; ⑤ Expected survival ≥ 90 days;

      • The major organs function normally; ⑦ The subject voluntarily joined this study, signed the informed consent, complied well and cooperated with the follow-up.

Exclusion Criteria:

• Had participated in other clinical trialists of drugs within 4 weeks before the start of the study;

  • Those who had hypertension that was inadequately controlled with a single antihypertensive agent (systolic blood pressure > 140 mmHg and diastolic blood pressure > 90 mmHg, as judged by the investigator), had myocardial ischemia or myocardial infarction of grade I or higher, arrhythmia of grade I and higher (including QT interval ≥ 440 MS), or cardiac dysfunction;

    • Those with a history of substance abuse who are unable to abstain or who have a history of mental disorders;

      • Presence of fungal, bacterial, viral, or other infections that are not controllable or require antibiotic therapy;

        • For subjects with prior chemotherapy use, ≥ grade 2 hematologic toxicity, or ≥ grade 3 nonhematologic toxicity according to nci-ctcae 5.0 criteria at enrollment; ⑥ Known presence of a history of HIV, or hepatitis B (HBsAg positive) or hepatitis C virus (anti HCV positive) nucleic acid test positive;

          • Presence of any indwelling catheter or drain (eg, biliary drain or pleural / peritoneal / pericardial catheter). Use of a dedicated central venous catheter was permitted (colostomy for patients with bowel cancer, percutaneous nephrostomy tube, indwelling Frey catheter, considered by the investigator for implications); ⑧ Presence of brain metastases, presence of a history or disease of the CNS such as seizure disorders, cerebral ischemia / hemorrhage, dementia, cerebellar disease, or any autoimmune disease involving the CNS;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CIK combined with chemotherapy group; Combination of CIK cells and chemotherapy	Combination product: CIK combined with chemotherapy group; Combination of chemotherapy and autologous cytokine induced killer cells
Experimental: CIK combined immunotherapy group; Combination of CIK cells and immunotherapy	Combination product: CIK combined immunotherapy group; Combination of immunotherapy and autologous cytokine induced killer cells
Experimental: CIK combined targeted therapy group; Combination of CIK cells and targeted therapy	Combination product: CIK combined targeted therapy group; Combination of targeted therapy and autologous cytokine induced killer cells
Experimental: CIK in combination with other therapies; CIK in combination with any two or three of these (i.e., chemotherapy, immunotherapy, and targeted therapy) treatments	Combination product: CIK in combination with other therapies; CIK combined with any two or three of them (i.e. chemotherapy, immunotherapy and targeted therapy)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease control rate (DCR)	Disease control rate of colorectal cancer	up to 5 years
objective response rate (ORR)	objective response rate of colorectal cancer	up to 5 years

Collaborators and Investigators

• Sponsor: ShiCang Yu

Publications and helpful links

General Publications

• Gammaitoni L, Giraudo L, Macagno M, Leuci V, Mesiano G, Rotolo R, Sassi F, Sanlorenzo M, Zaccagna A, Pisacane A, Senetta R, Cangemi M, Cattaneo G, Martin V, Coha V, Gallo S, Pignochino Y, Sapino A, Grignani G, Carnevale-Schianca F, Aglietta M, Sangiolo D. Cytokine-Induced Killer Cells Kill Chemo-surviving Melanoma Cancer Stem Cells. Clin Cancer Res. 2017 May 1;23(9):2277-2288. doi: 10.1158/1078-0432.CCR-16-1524. Epub 2016 Nov 4.
• Garofano F, Gonzalez-Carmona MA, Skowasch D, Schmidt-Wolf R, Abramian A, Hauser S, Strassburg CP, Schmidt-Wolf IGH. Clinical Trials with Combination of Cytokine-Induced Killer Cells and Dendritic Cells for Cancer Therapy. Int J Mol Sci. 2019 Sep 3;20(17):4307. doi: 10.3390/ijms20174307.
• Dienstmann R, Mason MJ, Sinicrope FA, Phipps AI, Tejpar S, Nesbakken A, Danielsen SA, Sveen A, Buchanan DD, Clendenning M, Rosty C, Bot B, Alberts SR, Milburn Jessup J, Lothe RA, Delorenzi M, Newcomb PA, Sargent D, Guinney J. Prediction of overall survival in stage II and III colon cancer beyond TNM system: a retrospective, pooled biomarker study. Ann Oncol. 2017 May 1;28(5):1023-1031. doi: 10.1093/annonc/mdx052.

Study record dates

Study Major Dates

• Study Start (Anticipated): January 9, 2023
• Primary Completion (Anticipated): December 30, 2026
• Study Completion (Anticipated): April 30, 2027

Study Registration Dates

• First Submitted: December 8, 2022
• First Submitted That Met QC Criteria: January 6, 2023
• First Posted (Estimate): January 9, 2023

Study Record Updates

• Last Update Posted (Estimate): January 9, 2023
• Last Update Submitted That Met QC Criteria: January 6, 2023
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Autologous cytokine induced killer cells
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: zsyx2

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