Intervention of Ovarian Cancer With Antigen-specific Engineered Immune Effectors

Study Overview
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Brief Summary
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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
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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.

Official Title
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Interventional Treatment of Ovarian Cancer With Cancer Antigen-specific Engineered Immune Effector T Lymphocytes (OC-EIEs)

Conditions
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Ovarian Cancer

Intervention / Treatment
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* Biological: OC-EIEs


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written, informed consent obtained prior to any study-specific procedures. Age older than 10 years. Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1. Expected survival ≥ 12 weeks. Histologically confirmed and documented high risk International Federation of Gynecology and Obstetrics (FIGO): Stage II-IV. Not pregnant, and on appropriate birth control of childbearing potential. Initial hematopoietic reconstitution with neutrophils (ANC) ≥ 1,000/mm^3; platelet (PLT) ≥ 100,000/mm^3. 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. Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) test negative. Exclusion Criteria: Patients with ovarian tumors with low malignant potential (i.e. borderline tumors); Patients with evidence of abdominal free air not explained by paracentesis or recent surgical procedure (prior, current or planned treatment). Prior treatment of any adoptive T cell therapy. Current or recent treatment (within the 14-day period prior to Day 0) with any immune suppressive drug Minor surgical procedures within 2 days prior to Day 0 (including central venous access device placement for chemotherapy administration, tumor biopsies, needle aspirations). Pregnant or lactating females. Inadequate bone marrow function with absolute neutrophil count < 1,000/mm^3; platelet count < 100,000/mm^3; Hb < 9 g/dL. 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. Serious active infection requiring i.v. antibiotics Subject infected with HCV (HCV antibody positive), or HIV (HIV antibody positive),Treponema pallidum antibody positive or TB culture positive.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OC-EIEs<br>Autologous ovarian cancer antigen-specific cytotoxic lymphocytes | Biological: OC-EIEs<br>* 2 to 4 infusions, once a week, 0.1 4x10^6 CTLs/kg; injection via IV, abdominal cavity or intrastumoral.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of OC-EIEs in patients using CTCAE version 4.0 standard to evaluate the level of adverse events | percentage of patients with grade 3 or above adverse effect | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Expansion of OC-EIEs | The increased fold of specificity of OC-EIEs, will be analyzed by enzyme-linked immunospot assay (ELISPOT) | 8 weeks. | 
| percentage of complete response | Objective response will be assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. | 1 year | 
| percentage of partial response | Objective response will be assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. | 1 year | 
| percentage of stable disease | Objective response will be assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. | 1 year | 
| percentage of progressive disease | Objective response will be assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ovarian cancer, Cytotoxic lymphocyte, Cancer specific antigen