Engineered Immune Effectors Against Cervical Cancer

Phase 1

• Conditions: Cervical Cancer
• Interventions: Biological: CC-EIEs

• Registration Number: NCT03362619
• Lead Sponsor: Shenzhen Geno-Immune Medical Institute

Brief Summary

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.

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 Timeline

• Study Start: 2017-11-15
• Study First Submitted: 2017-11-20
• Study First Submitted QC: 2017-11-29
• Study First Posted: 2017-12-05
• Primary Completion: 2019-01-31
• Status Verified: 2019-09
• Last Update Submitted: 2019-09-18
• Last Update Posted: 2019-09-19
• Study Completion: 2020-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 20

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CC-EIEs	CC-EIEs	Autologous cervical cancer specific engineered immune effectors (EIEs)

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Functional analyses of CC-EIEs in vitro	4 weeks	The specificity of CC-EIEs in vitro will be analysed by enzyme-linked immunospot assay (ELISPOT).
Anti-tumor effects	1 year	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.

Trial Locations

Locations (3)

Shenzhen Geno-immune Medical Institute; 🇨🇳 Shenzhen, Guangdong, China

Jinshazhou Hospital of Guangzhou University of Chinese Medicine; 🇨🇳 Guangzhou, Guangdong, China

Yunnan Cancer Hospital & The Third Affiliated Hospital of Kunming Medical University & Yunnan Cancer Center; 🇨🇳 Kunming, Yunnan, China