T Cell Mediated Adaptive Therapy for Her2-positive Neoplasms of Digestive System

Phase 1

• Conditions: Pancreatic Cancer; Liver Cancer; Bowel Cancer; Esophageal Cancer; Gastric Cancer; Gallbladder Cancer
• Interventions: Drug: HER2Bi-Armed T Cells; Drug: Recombinant Human Interleukin-2

• Registration Number: NCT02662348
• Lead Sponsor: Yi Miao

Brief Summary

This phase I trial is to investigate the safety and the possible side effects of bi-specific antibody armed T-cell therapy when given together with low-dose IL-2 in treating patients with Her2-positive neoplasms of digestive system. Expanded autologues T cells that have been coated with bi-specific antibodies, such as anti-CD3 and anti-human epidermal growth factor receptor 2 (HER2), may stimulate the immune system in different ways and stop tumor cells from growing. Interleukin-2 may stimulate white blood cells to kill tumor cells.

Detailed Description

PRIMARY OBJECTIVES:

I. Perform a phase I clinical trial to clearly define the toxicity profile of IV HER2Bi armed T cells in patients with neoplasms of digestive system.

SECONDARY OBJECTIVES:

I. Evaluate phenotype, cytokine profiles and tumor markers, cytotoxicity directed at laboratory Her2 positive cancer cell lines.

II. Evaluate the clinical symptoms and signs, clinical responses, imaging examination of pretherapy and post-treatment, cytokine profiles and tumor markers in serum before and after treatment, time to progression, and overall survival.

OUTLINE: This is a safety study of IV infused HER2Bi-armed activated T cells. Patients receive HER2Bi armed T cells IV weekly for 4 weeks. Patients also receive low-dose Interleukin subcutaneously (SC) daily beginning 3 days before the first HER2Bi armed T cells infusion. Treatment continues in the absence of disease progression or unacceptable toxicity.

Study Timeline

• Status Verified: 2016-01
• Study First Submitted: 2016-01-20
• Study First Submitted QC: 2016-01-20
• Last Update Submitted: 2016-01-20
• Study First Posted: 2016-01-25
• Last Update Posted: 2016-01-25
• Study Start: 2016-02
• Primary Completion: 2017-11
• Study Completion: 2017-11

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 6

Inclusion Criteria

1. Patient with Her2-positive neoplasms of digestive system: IHC 3+
2. Clinical staging: Phase III or above
3. Ages: < 65
4. Expected survival time: > 1 year
5. Quality of Life: > 60
6. The functions of important organs( heart, liver, lung, kidney and etc.)are normal
7. The volunteers with informed consent

Exclusion criteria:

1. Patient with Her2-negative neoplasms of digestive system
2. Hepatic renal dysfunction
3. Cardiopulmonary insufficiency
4. Mental disorder
5. Allergic condition
6. With other malignant tumor
7. Lactating women
8. Patients with infection or received chemotherapy in the past two weeks
9. Patient with autoimmune disease using immunosuppressive drug
10. Patient with organ transplantation with long term use of immunosupresive drug

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
T Cells Transfusion	HER2Bi-Armed T Cells	Patients receive HER2Bi-Armed T Cells IV weekly for 4 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.
Interleukin-2 Transfusion	Recombinant Human Interleukin-2	Patients receive low-dose Recombinant Human Interleukin-2 SC daily beginning 3 days before the first HER2Bi armed T cell infusions infusion.

Primary Outcome Measures

Name	Time	Method
Safety as measured by local and systemic toxicities	Up to 1 year

Secondary Outcome Measures

Name	Time	Method
Changes in cytokine profiles and tumor markers in serum before and after treatment	Baseline to up to 12 months	Increases or decreases in the amount of cytokine produced from the pre-immunotherapy baseline at any time point after immunotherapy will be considered as continuous outcomes.
Changes in phenotyping induced by immunotherapy in peripheral blood mononuclear cells (PBMC)	Baseline to up to 12 months	PBMC from the patients will be obtained before and after immunotherapy to determine if there are any phenotype changes induced by immunotherapy. Paired t-test will be used to compare the difference between baseline and after any time point of armed T cells treatment in T cell subpopulation (FACS), tumor marker (CBA/ELISA) and tumor killing ability of PBMC.
Clinical response rate (including clinical symptoms and signs, complete response, partial response, progressive disease, and stable disease, imaging examination of pretherapy and post-treatment) will be measured by follow-up investigation.	Up to 12 months	Point and exact confidence interval estimates will be calculated for response rate.
Overall survival	Up to 12 months	Will be estimated with the standard Kaplan-Meier method, from which summary statistics of interest (median, 6 month, 1-year rate, etc.) will be derived. Both point and 95% confidence interval estimates will be calculated.
Progression free survival	From the beginning of immunotherapy to progression or death, assessed up to 12 months	Will be estimated with the standard Kaplan-Meier method, from which summary statistics of interest (median, 6 month, 1-year rate, etc.) will be derived. Both point and 95% confidence interval estimates will be calculated.