Immunotherapy Treating GI Cancer

NCT ID: NCT03614650

Last Updated: 2018-08-03

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-01
• Study Completion Date: 2021-12-31

Brief Summary

The primary objectives are to evaluate the safety and efficacy of infusion of autologous gastro-intestinal (GI) cancer antigen-specific engineered immune effector cells (EIE).

Detailed Description

Gastro-intestinal (GI) cancer is becoming the top-ranked high mortality cancer in recent years. Every year, approximate 5,300,000 people in China are diagnosed with cancer, of which about 2,000,000 die each year, and esophagus cancer, gastric cancer and colorectal cancer account for ~50% of all GI cancer cases. GI cancer causes 500 thousand deaths a year. In China, nearly 85% of patients with cancer of the digestive tract are in middle to late stage at diagnosis. Regardless of the treatment, the five year survival rate is only 36%. GI cancers include cancer in the oral cavity, pharynx, esophagus, stomach, small intestine (duodenum, jejunum, ileum) and large intestine (cecum, colon, rectum). The main malignant tumors of the GI tract are esophageal, gastric, colorectal, liver, and pancreatic cancer.

Adoptive immunotherapy based on cytotoxic T lymphocytes reactive with specific antigens has proven to be effective in many studies. In vitro induction of cancer antigen-specific immune cells and genetic engineering of target specific immune cells have great potential for cancer eradication. This study aims to evaluate the safety and efficacy of ex vivo manipulated EIE cells including chimeric antigen receptor (CAR) modified immune cells in treating cancer. The primary study objectives are to evaluate the safety of the investigational product, autologous EIE cells, to subjects by intravenous and intratumoral injections. The secondary study objectives are (1) to evaluate the success rate of generating autologous EIE cells ex vivo, and (2) to determine the anti-cancer efficacy of the EIE cells.

Conditions

Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

EIE cells to treat cancer

EIE cells to treat cancer

Group Type: EXPERIMENTAL

engineered immune cells

Intervention Type: BIOLOGICAL

Engineered immune effector cells (EIE)

Interventions

engineered immune cells

Engineered immune effector cells (EIE)

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• 1. Written, informed consent obtained prior to any study-specific procedures. 2. The results of immune staining of the patient's cancer specimens positive for any one or more of tumor-associated antigens, such as GD2, mesothelin, CEA, P16, MMP, Melan A, MAGE A1, MAGE A3, and MAGE A4.

3. Eastern Cooperative Oncology Group (ECOG) PS of 0, 1 or 2. 4. Life expectancy ≥ 3 months. 5. Able to comply with the protocol. 6. Histologically confirmed and documented high risk International Federation of Gynecology and Obstetrics (FIGO): Stage III-IV.

7. Not pregnant, and on appropriate birth control if of childbearing potential. 8. Adequate bone marrow reserve with

• absolute neutrophil count (ANC) ≥ 1000/mm3.• Platelets ≥100,000/mm3. 9. Adequate renal and hepatic function with• Serum creatinine ≤ 2 x upper limit of normal (ULN).• Serum bilirubin ≤ 2 x ULN.• aspartate aminotransferase (AST)/ALT ≤ 2 x ULN.• Alkaline phosphatase ≤ 5 x ULN.• Serum bilirubin. 2.0 is acceptable in the setting of known Gilbert's syndrome.

Exclusion Criteria

• 1. The results of immune staining of the patient's tumor-associated antigens are all negative.

2. Participation in any other cell therapy protocols within one year. 3. Current or recent treatment (within the 28-day period prior to Day 0) with another investigational drug.

4. Minor surgical procedures within 2 days prior to Day 0 (including central venous access device placement for chemotherapy administration, tumor biopsies, needle aspirations).

5. Pregnant or lactating females. 6. Unable to comply with the trial related requirement. 7. Inadequate bone marrow function:

• Absolute neutrophil count < 1.0 x 10e9/L.
• Platelet count < 100 x 10e9/L.
• Hb < 9 g/dL.

Inadequate liver and renal function:

• 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 (or > 5 x ULN in case of liver metastases or > 10 x ULN in case of bone metastases).
• 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.

8. Serious active infection requiring i.v. antibiotics during screening. 10. Subject infected with HIV (HIV antibody positive), Treponema pallidum antibody positive or TB culture positive.

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shenzhen Geno-Immune Medical Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lung-Ji Chang, PhD

Role: STUDY_CHAIR

Shenzhen Geno-Immune Medical Institute

Locations

Shenzhen Geno-immune Medical Institute

Shenzhen, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Lung-Ji Chang, PhD

Role: CONTACT

c@szgimi.org

86-075586725195

Facility Contacts

Lung-Ji Chang, PhD

Role: primary

c@szgimi.org

86-075586725195

Yichun Cai, MD

Role: backup

86-13802830754

Other Identifiers

GIMI-IRB-18002

Identifier Type: -

Identifier Source: org_study_id