Intervention of Ovarian Cancer With Antigen-specific Engineered Immune Effectors

Ovarian Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT03393962
• Other study ID #: GIMI-IRB-17024
• Status: Suspended
• Phase: Phase 1/Phase 2
• Start date: December 1, 2017
• Est. completion date: December 2020

Study information

• Verified date: July 2018
• Source: Shenzhen Geno-Immune Medical Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 20
• Est. completion date: December 2020
• Est. primary completion date: January 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 10 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Neoplasms, Glandular and Epithelial
• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Biological:
• OC-EIEs
2 to 4 infusions, once a week, 0.1~4x10^6 CTLs/kg; injection via IV, abdominal cavity or intrastumoral.

Locations

Country	Name	City	State
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	Shenzhen Geno-immune Medical Institute	Shenzhen	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Shenzhen Geno-Immune Medical Institute

Country where clinical trial is conducted

China, 

Outcome

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