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

Pancreatic Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT02662348
• Other study ID #: 2013-SR-116.F1
• Status: Enrolling by invitation
• Phase: Phase 1
• First received: January 20, 2016
• Last updated: January 20, 2016
• Start date: February 2016
• Est. completion date: November 2017

Study information

• Verified date: January 2016
• Source: The First Affiliated Hospital with Nanjing Medical University
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 6
• Est. completion date: November 2017
• Est. primary completion date: November 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bowel Cancer
• Digestive System Neoplasms
• Esophageal Cancer
• Esophageal Neoplasms
• Gallbladder Cancer
• Gastric Cancer
• Gastrointestinal Neoplasms
• Liver Cancer
• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Drug:
• Recombinant Human Interleukin-2
Given SC
• HER2Bi-Armed T Cells
Given IV

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Yi Miao	Abingen Ltd, Nanjing

Country where clinical trial is conducted

China, 

References & Publications (26)

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Davol PA, Smith JA, Kouttab N, Elfenbein GJ, Lum LG. Anti-CD3 x anti-HER2 bispecific antibody effectively redirects armed T cells to inhibit tumor development and growth in hormone-refractory prostate cancer-bearing severe combined immunodeficient beige mice. Clin Prostate Cancer. 2004 Sep;3(2):112-21. — View Citation

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* Note: There are 26 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety as measured by local and systemic toxicities		Up to 1 year	Yes
Secondary	Changes in cytokine profiles and tumor markers in serum before and after treatment	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.	Baseline to up to 12 months	No
Secondary	Changes in phenotyping induced by immunotherapy in peripheral blood mononuclear cells (PBMC)	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.	Baseline to up to 12 months	No
Secondary	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.	Point and exact confidence interval estimates will be calculated for response rate.	Up to 12 months	No
Secondary	Overall survival	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.	Up to 12 months	No
Secondary	Progression free survival	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.	From the beginning of immunotherapy to progression or death, assessed up to 12 months	No