Clinical trial NCT03614650: Immunotherapy Treating GI Cancer
Official title: Antigen-specific Engineered Immune Effector Cells (EIE) Against Gastro-Intestinal (GI) Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Cancer
Keywords: immunotherapyT cellGI cancergene therapy
Lead sponsor: Shenzhen Geno-Immune Medical Institute
Sponsor class: OTHER
First posted: 2018-08-03
Enrollment: 100
Sex: ALL
Minimum age (years): 1
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: percentage of adverse effects after EIE cell injection
timeFrame: up to one month
Secondary outcomes:
measure: Rate of successful EIE generation
timeFrame: up to one month
measure: Ability of EIE cells to reduce cancer burden
timeFrame: after 1 month from EIE cells infusion until 12 months after infusion
measure: The anti-cancer effects
timeFrame: after 1 month from EIE cells infusion until 24 months after infusion
Other outcomes:
Locations:
city: Shenzhen
country: China
facility: Shenzhen Geno-immune Medical Institute
state: Guangdong
Study officials:
affiliation: Shenzhen Geno-Immune Medical Institute
name: Lung-Ji Chang, PhD
role: STUDY_CHAIR
References: