Engineered Immune Effectors Against Cervical Cancer

Innovative Treatment of Cervical Cancer Using Engineered Antigen-specific Immune Effectors (EIEs)

The primary objective of this study is to evaluate the safety of cervical cancer specific engineered immune effectors (CC-EIEs). The secondary objectives are to evaluate the rate of successful CC-EIE generation in vitro and determine the anti-CC efficacy.

Study Overview

• Status: Unknown
• Conditions: Cervical Cancer
• Intervention / Treatment: Biological: CC-EIEs

Detailed Description

Cervical cancer (CC) is a cancer arising from the cervix. Human papillomavirus (HPV) infection causes more than 90% of the cases. Other risk factors include smoking, a weak immune system, birth control pills, starting sex at a young age, and having many sexual partners, but these are less important. Worldwide, CC is both the fourth-most common cause of cancer and the fourth-most common cause of death from cancer in women. The treatment of CC consists of surgical intervention, radiation, chemotherapy and immunotherapy.

Adoptive immunotherapy with cytotoxic T lymphocytes reactive with specific viral antigens has proven to be effective. Here, the investigators aim to evaluate the safety and efficacy of multiple infusions of CC-specific engineered immune effectors including cytotoxic T lymphocytes in patients.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510415
      • Recruiting
      • Jinshazhou Hospital of Guangzhou University of Chinese Medicine
      • Contact: Qichun Cai, MD; Phone Number: 86-13802830754
    • Shenzhen, Guangdong, China, 518000
      • Recruiting
      • Shenzhen Geno-immune Medical Institute
  • Yunnan
    • Kunming, Yunnan, China, 650000
      • Recruiting
      • Yunnan Cancer Hospital & The Third Affiliated Hospital of Kunming Medical University & Yunnan Cancer Center
      • Contact: Xun Lai, MD; Phone Number: 13577096609; Email: 1729112214@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 80 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Written, informed consent obtained prior to any study-specific procedures.
2. Age older than 10 years.
3. Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1.
4. Expected survival ≥ 12 weeks.
5. Not pregnant, and on appropriate birth control if of childbearing potential.
6. Evidence of high-risk HPV infection.
7. Stage III-IV or recurrent cervical cancer.

8. Initial hematopoietic reconstitution with

   • neutrophils (ANC) ≥ 1,000/mm^3;
   • platelet (PLT) ≥ 100,000/mm^3.

9. Proper renal and hepatic functions (ULN denotes "upper limit of normal range") with

   • serum creatinine ≤ 2×ULN;
   • serum bilirubin ≤ 2×ULN;
   • AST/ALT ≤ 2×ULN;
   • ALKP ≤ 5×ULN;
   • serum bilirubin. 2.0 is acceptable in the setting of known Gilbert's syndrome.
10. Human immunodeficiency virus (HIV) and Hepatitis C virus (HCV) test negative.

Exclusion Criteria:

1. Patients with

   • cervical benign lesions: cervical columnar epithelium ectopic, cervical polyps, cervical endometriosis and cervical tuberculous ulcers;
   • cervical benign tumors: cervical submucous myoma, cervical cancer, cervical papilloma.
2. Patients with evidence of abdominal free air not explained by paracentesis or recent surgical procedure (prior, current or planned treatment).
3. Previous exposure to mouse SCC antibody.
4. Current or recent treatment (within the 28-day period prior to Day 0) with another investigational drug or previous participation in this study.
5. Minor surgical procedures within 2 days prior to Day 0 (including central venous access device placement for chemotherapy administration, tumor biopsies, needle aspirations).
6. Pregnant or lactating females.

7. Inadequate bone marrow function with

   • absolute neutrophil count < 1,000/mm^3;
   • platelet count < 100,000/mm^3;
   • Hb < 9 g/dL.

8. Inadequate liver and renal function with

   • serum (total) bilirubin > 1.5 x ULN;
   • AST & ALT > 2.5 x ULN (> 5 x ULN in patients with liver metastases);
   • alkaline phosphatase > 2.5 x ULN;
   • serum creatinine >2.0 mg/dl (> 177 μmol/L);
   • urine dipstick for protein uria should be < 2+. Patients with ≥ 2+ proteinuria on dipstick urinalysis at baseline should undergo 24 hour urine collection and must demonstrate < 1 g of protein/24 hr.
9. Serious active infection requiring i.v. antibiotics at during screening.
10. Subject actively infected with HCV (HCV antibody positive), HBV (HBsAg positive), HIV (HIV antibody positive), HTLV (HTLV antibody positive), Treponema pallidum antibody positive or TB culture positive.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CC-EIEs; Autologous cervical cancer specific engineered immune effectors (EIEs)	Biological: CC-EIEs; 2 to 4 infusions, once a week, for 1x10^5~1x10^7 CTLs/kg via IV, abdominal cavity or intratumoral injection each time

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of CC-EIEs in patients using CTCAE version 4.0 standard to evaluate the level of adverse events	Physiological parameter (measuring cytokine response, fever, symptoms)	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-tumor effects	Objective response, such as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) will be assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.	1 year
Functional analyses of CC-EIEs in vitro	The specificity of CC-EIEs in vitro will be analysed by enzyme-linked immunospot assay (ELISPOT).	4 weeks

Collaborators and Investigators

• Sponsor: Shenzhen Geno-Immune Medical Institute
• Investigators: Study Director: Qichun Cai, MD, Jinshazhou Hospital of Guangzhou University of Chinese Medicine; Study Director: Xun Lai, MD, Yunnan Cancer Hospital & The Third Affiliated Hospital of Kunming Medical University & Yunnan Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2017
• Primary Completion (Actual): January 31, 2019
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: November 20, 2017
• First Submitted That Met QC Criteria: November 29, 2017
• First Posted (Actual): December 5, 2017

Study Record Updates

• Last Update Posted (Actual): September 19, 2019
• Last Update Submitted That Met QC Criteria: September 18, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Cervical cancer; Cytotoxic lymphocyte; CC-CTL
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Uterine Cervical Neoplasms
• Other Study ID Numbers: GIMI-IRB-17019

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