Immunotherapy Treating GI Cancer

• ClinicalTrials.gov Identifier: NCT03614650
• Recruitment Status: Unknown
• First Posted: August 3, 2018
• Last Update Posted: August 3, 2018
• Sponsor: Shenzhen Geno-Immune Medical Institute
• Information provided by (Responsible Party): Shenzhen Geno-Immune Medical Institute

Tracking Information

• First Submitted Date: July 23, 2018
• First Posted Date: August 3, 2018
• Last Update Posted Date: August 3, 2018
• Actual Study Start Date: July 1, 2018
• Estimated Primary Completion Date: June 30, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 30, 2018)

percentage of adverse effects after EIE cell injection [ Time Frame: up to one month ]

To assess the safety of autologous EIE cells in patients. The percentage of patients who have adverse effects will be evaluated by using the NCI CTCAE V4.0 criteria.

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: July 30, 2018)

• Rate of successful EIE generation [ Time Frame: up to one month ]
  The percentage of successful EIE generation, which are derived from subjects and pass the safety test after standard culture procedures, viable for at least one preparation, will be evaluated.
• Ability of EIE cells to reduce cancer burden [ Time Frame: after 1 month from EIE cells infusion until 12 months after infusion ]
  measurement of tumor marker in blood and examination of tumor size change
• The anti-cancer effects [ Time Frame: after 1 month from EIE cells infusion until 24 months after infusion ]
  Objective response (complete response (CR) + partial response (PR)) are assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. CR is disappearance of all lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Immunotherapy Treating GI Cancer
• Official Title: Antigen-specific Engineered Immune Effector Cells (EIE) Against Gastro-Intestinal (GI) Cancer
• 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.

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Cancer

Intervention

Biological: engineered immune cells

Engineered immune effector cells (EIE)

Study Arms

Experimental: EIE cells to treat cancer

EIE cells to treat cancer

Intervention: Biological: engineered immune cells

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: July 30, 2018): 100
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2021
• Estimated Primary Completion Date: June 30, 2021 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Year to 80 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT03614650
• Other Study ID Numbers: GIMI-IRB-18002
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Shenzhen Geno-Immune Medical Institute
• Original Responsible Party: Same as current
• Current Study Sponsor: Shenzhen Geno-Immune Medical Institute
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Lung-Ji Chang, PhD; Shenzhen Geno-Immune Medical Institute

• PRS Account: Shenzhen Geno-Immune Medical Institute
• Verification Date: July 2018