Clinical trial NCT03362619: Engineered Immune Effectors Against Cervical Cancer
Official title: Innovative Treatment of Cervical Cancer Using Engineered Antigen-specific Immune Effectors (EIEs)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Cervical Cancer
Keywords: Cervical cancer
Cytotoxic lymphocyte
CC-CTL
Lead sponsor: Shenzhen Geno-Immune Medical Institute
Sponsor class: OTHER
First posted: 2017-12-05
Enrollment: 20
Sex: FEMALE
Minimum age (years): 10
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Safety of CC-EIEs in patients using CTCAE version 4.0 standard to evaluate the level of adverse events
timeFrame: 6 months
Secondary outcomes:
measure: Functional analyses of CC-EIEs in vitro
timeFrame: 4 weeks
measure: Anti-tumor effects
timeFrame: 1 year
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Jinshazhou Hospital of Guangzhou University of Chinese Medicine
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen Geno-immune Medical Institute
state: Guangdong
city: Kunming
country: China
facility: Yunnan Cancer Hospital & The Third Affiliated Hospital of Kunming Medical University & Yunnan Cancer Center
state: Yunnan
Study officials:
affiliation: Shenzhen Geno-Immune Medical Institute
name: Lung-Ji Chang, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Jinshazhou Hospital of Guangzhou University of Chinese Medicine
name: Qichun Cai, MD
role: STUDY_DIRECTOR
affiliation: Yunnan Cancer Hospital & The Third Affiliated Hospital of Kunming Medical University & Yunnan Cancer Center
name: Xun Lai, MD
role: STUDY_DIRECTOR
References: