Clinical trial NCT03393962: Intervention of Ovarian Cancer With Antigen-specific Engineered Immune Effectors
Official title: Interventional Treatment of Ovarian Cancer With Cancer Antigen-specific Engineered Immune Effector T Lymphocytes (OC-EIEs)
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE1
PHASE2
Conditions: Ovarian Cancer
Keywords: Ovarian cancer
Cytotoxic lymphocyte
Cancer specific antigen
Lead sponsor: Shenzhen Geno-Immune Medical Institute
Sponsor class: OTHER
First posted: 2018-01-09
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: This is a single-arm, open-label, phase I/II trial to evaluate the safety and efficacy of ovarian cancer-specific, engineered immune effectors (OC-EIEs) in women.

Detailed description: Ovarian cancer (OC) is a cancer that is derived from an ovary. The majority of OC arises from the epithelium (outer lining) of the ovary. In 2015, OC was found in 1.2 million women and resulted in 161,100 deaths worldwide. Among women, OC is the seventh-most common cancer and the eighth-most common cause of cancer death. Treatment for OC consists of surgery, chemotherapy, immunotherapy and radiotherapy. The kind of treatment depends on many factors, including the type of OC, its stage and grade, as well as the general health of the patient.

Adoptive immunotherapy with cytotoxic T lymphocytes (CTLs) reactive with tumor antigens has proven to be effective against many types of cancer. OC has been shown to be highly immunogenic and therefore may respond well to innovative antigen-specific immunotherapy. Here, through cancer antigen screening and careful target antigen evaluation, the investigation aims to evaluate the safety and efficacy of multiple infusions of OC antigen-specific, engineered immune effectors (EIEs) in patients with OC.

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. Histologically confirmed and documented high risk International Federation of Gynecology and Obstetrics (FIGO): Stage II-IV.
6. Not pregnant, and on appropriate birth control of childbearing potential.
7. Initial hematopoietic reconstitution with

   * neutrophils (ANC) ≥ 1,000/mm\^3;
   * platelet (PLT) ≥ 100,000/mm\^3.
8. 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.
9. Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) test negative.

Exclusion Criteria:

1. Patients with ovarian tumors with low malignant potential (i.e. borderline tumors);
2. Patients with evidence of abdominal free air not explained by paracentesis or recent surgical procedure (prior, current or planned treatment).
3. Prior treatment of any adoptive T cell therapy.
4. Current or recent treatment (within the 14-day period prior to Day 0) with any immune suppressive drug
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
10. Subject infected with HCV (HCV antibody positive), or HIV (HIV antibody positive),Treponema pallidum antibody positive or TB culture positive.

Primary outcomes:
measure: Safety of OC-EIEs in patients using CTCAE version 4.0 standard to evaluate the level of adverse events
timeFrame: 6 months
Secondary outcomes:
measure: Expansion of OC-EIEs
timeFrame: 8 weeks.
measure: percentage of complete response
timeFrame: 1 year
measure: percentage of partial response
timeFrame: 1 year
measure: percentage of stable disease
timeFrame: 1 year
measure: percentage of progressive disease
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: