Intervention of Ovarian Cancer With Antigen-specific Engineered Immune Effectors

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

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.

Study Overview

• Status: Suspended
• Conditions: Ovarian Cancer
• Intervention / Treatment: Biological: OC-EIEs

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.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510415
      • Jinshazhou Hospital of Guangzhou University of Chinese Medicine
    • Shenzhen, Guangdong, China, 518000
      • Shenzhen Geno-Immune Medical Institute
  • Yunnan
    • Kunming, Yunnan, China, 650000
      • Yunnan Cancer Hospital & The Third Affiliated Hospital of Kunming Medical University & Yunnan Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 80 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Shenzhen Geno-Immune Medical Institute
• Investigators: Study Director: Qichun Cai, MD, Jinshazhou Hospital of Guangzhou University of Chinese Medicine; Study Director: Xun Lai, MD, Yunnan Cancer Hospital & The Third Affiliated Hospital of Kunming Medical University & Yunnan Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2017
• Primary Completion (Anticipated): January 1, 2020
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: December 28, 2017
• First Submitted That Met QC Criteria: January 3, 2018
• First Posted (Actual): January 9, 2018

Study Record Updates

• Last Update Posted (Actual): July 31, 2018
• Last Update Submitted That Met QC Criteria: July 30, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Ovarian cancer; Cytotoxic lymphocyte; Cancer specific antigen
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
• Other Study ID Numbers: GIMI-IRB-17024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No