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Esophageal CancerPhase 1NCT02662348

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

A Phase 1 study testing Recombinant Human Interleukin-2 and HER2Bi-Armed T Cells in people with Esophageal Cancer and Gastric Cancer, run by Yi Miao at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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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. Read more about this study

Who is it for?
Ages 18 to 65 years
What is being tested?
Recombinant Human Interleukin-2 and HER2Bi-Armed T Cells
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
1 siteChina
Study dates
Feb 2016to Nov 2017
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

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

Who cannot join

  • Patient with Her2-negative neoplasms of digestive system
  • Hepatic renal dysfunction
  • Cardiopulmonary insufficiency
  • Mental disorder
  • Allergic condition
  • With other malignant tumor
Show all 10Show fewer
  • Lactating women
  • Patients with infection or received chemotherapy in the past two weeks
  • Patient with autoimmune disease using immunosuppressive drug
  • Patient with organ transplantation with long term use of immunosupresive drug

Trial locations and contacts

1 site in 1 country.

China1 site

  • Study site

    Nanjing, Jiangsu

Other trials in China

About this study

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

Being tested
Recombinant Human Interleukin-2, HER2Bi-Armed T Cells
Medical subject headings
Esophageal Neoplasms, Stomach Neoplasms, Pancreatic Neoplasms, Liver Neoplasms, Gallbladder Neoplasms, Intestinal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Recombinant Human Interleukin-2Drug

    Also called Proleukin, Recombinant Human IL-2

    Given SC

  • HER2Bi-Armed T CellsDrug

    Also called HER2Bi-Armed ATCs

    Given IV

Study groups in NCT02662348
Study groupRoleWhat they receive
Interleukin-2 TransfusionExperimentalPatients receive low-dose Recombinant Human Interleukin-2 SC daily beginning 3 days before the first HER2Bi armed T cell infusions infusion.
Receives: Drug: Recombinant Human Interleukin-2
T Cells TransfusionExperimentalPatients receive HER2Bi-Armed T Cells IV weekly for 4 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.
Receives: Drug: HER2Bi-Armed T Cells

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety as measured by local and systemic toxicities

    Measured: Up to 1 year

Secondary outcomes (5)

  1. 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.

    Measured: Baseline to up to 12 months

  2. 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.

    Measured: Baseline to up to 12 months

  3. 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.

    Measured: Up to 12 months

  4. 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.

    Measured: Up to 12 months

  5. 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.

    Measured: From the beginning of immunotherapy to progression or death, assessed up to 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Jan 2016 (estimated)
  2. Study startFeb 2016
  3. Primary completionNov 2017 (estimated)
  4. Study completionNov 2017 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
6 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02662348
Sponsor's protocol ID
2013-SR-116.F1
Status last verified
Jan 2016
First submitted
20 Jan 2016
Last updated
25 Jan 2016
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Yes: Nov 2017 ( Anticipated)

Publications

  • Molina MA, Codony-Servat J, Albanell J, Rojo F, Arribas J, Baselga J. Trastuzumab (herceptin), a humanized anti-Her2 receptor monoclonal antibody, inhibits basal and activated Her2 ectodomain cleavage in breast cancer cells. Cancer Res. 2001 Jun 15;61(12):4744-9.

    PubMed 11406546

  • Ross JS, Slodkowska EA, Symmans WF, Pusztai L, Ravdin PM, Hortobagyi GN. The HER-2 receptor and breast cancer: ten years of targeted anti-HER-2 therapy and personalized medicine. Oncologist. 2009 Apr;14(4):320-68. doi: 10.1634/theoncologist.2008-0230. Epub 2009 Apr 3.

    PubMed 19346299

  • Jorgensen JT. Targeted HER2 treatment in advanced gastric cancer. Oncology. 2010;78(1):26-33. doi: 10.1159/000288295. Epub 2010 Feb 25.

    PubMed 20185938

  • Camilleri-Broet S, Hardy-Bessard AC, Le Tourneau A, Paraiso D, Levrel O, Leduc B, Bain S, Orfeuvre H, Audouin J, Pujade-Lauraine E; GINECO group. HER-2 overexpression is an independent marker of poor prognosis of advanced primary ovarian carcinoma: a multicenter study of the GINECO group. Ann Oncol. 2004 Jan;15(1):104-12. doi: 10.1093/annonc/mdh021.

    PubMed 14679128

  • Janjigian YY, Werner D, Pauligk C, Steinmetz K, Kelsen DP, Jager E, Altmannsberger HM, Robinson E, Tafe LJ, Tang LH, Shah MA, Al-Batran SE. Prognosis of metastatic gastric and gastroesophageal junction cancer by HER2 status: a European and USA International collaborative analysis. Ann Oncol. 2012 Oct;23(10):2656-2662. doi: 10.1093/annonc/mds104. Epub 2012 Jun 11.

    PubMed 22689179

  • Takenaka M, Hanagiri T, Shinohara S, Kuwata T, Chikaishi Y, Oka S, Shigematsu Y, Nagata Y, Shimokawa H, Nakagawa M, Uramoto H, So T, Tanaka F. The prognostic significance of HER2 overexpression in non-small cell lung cancer. Anticancer Res. 2011 Dec;31(12):4631-6.

    PubMed 22199341

  • Mimura K, Kono K, Hanawa M, Kanzaki M, Nakao A, Ooi A, Fujii H. Trastuzumab-mediated antibody-dependent cellular cytotoxicity against esophageal squamous cell carcinoma. Clin Cancer Res. 2005 Jul 1;11(13):4898-904. doi: 10.1158/1078-0432.CCR-04-2476.

    PubMed 16000588

  • Pagni F, Zannella S, Ronchi S, Garanzini C, Leone BE. HER2 status of gastric carcinoma and corresponding lymph node metastasis. Pathol Oncol Res. 2013 Jan;19(1):103-9. doi: 10.1007/s12253-012-9564-2. Epub 2012 Aug 21.

    PubMed 22907801

  • Jorgensen JT, Hersom M. HER2 as a Prognostic Marker in Gastric Cancer - A Systematic Analysis of Data from the Literature. J Cancer. 2012;3:137-44. doi: 10.7150/jca.4090. Epub 2012 Mar 12.

    PubMed 22481979

  • Arnould L, Gelly M, Penault-Llorca F, Benoit L, Bonnetain F, Migeon C, Cabaret V, Fermeaux V, Bertheau P, Garnier J, Jeannin JF, Coudert B. Trastuzumab-based treatment of HER2-positive breast cancer: an antibody-dependent cellular cytotoxicity mechanism? Br J Cancer. 2006 Jan 30;94(2):259-67. doi: 10.1038/sj.bjc.6602930.

    PubMed 16404427

  • Hudis CA. Trastuzumab--mechanism of action and use in clinical practice. N Engl J Med. 2007 Jul 5;357(1):39-51. doi: 10.1056/NEJMra043186. No abstract available.

    PubMed 17611206

  • Krahn G, Leiter U, Kaskel P, Udart M, Utikal J, Bezold G, Peter RU. Coexpression patterns of EGFR, HER2, HER3 and HER4 in non-melanoma skin cancer. Eur J Cancer. 2001 Jan;37(2):251-9. doi: 10.1016/s0959-8049(00)00364-6.

    PubMed 11166154

  • Schuell B, Gruenberger T, Scheithauer W, Zielinski Ch, Wrba F. HER 2/neu protein expression in colorectal cancer. BMC Cancer. 2006 May 8;6:123. doi: 10.1186/1471-2407-6-123.

    PubMed 16681853

  • Kountourakis P, Pavlakis K, Psyrri A, Rontogianni D, Xiros N, Patsouris E, Pectasides D, Economopoulos T. Clinicopathologic significance of EGFR and Her-2/neu in colorectal adenocarcinomas. Cancer J. 2006 May-Jun;12(3):229-36. doi: 10.1097/00130404-200605000-00012.

    PubMed 16803682

  • Lum LG, Rathore R, Cummings F, Colvin GA, Radie-Keane K, Maizel A, Quesenberry PJ, Elfenbein GJ. Phase I/II study of treatment of stage IV breast cancer with OKT3 x trastuzumab-armed activated T cells. Clin Breast Cancer. 2003 Aug;4(3):212-7. doi: 10.3816/cbc.2003.n.028. No abstract available.

    PubMed 14499016

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Recombinant Human Interleukin-2 and HER2Bi-Armed T Cells in people with Esophageal Cancer and Gastric Cancer, run by Yi Miao at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 25 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety as measured by local and systemic toxicities (time frame: Up to 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02662348, which also lists 26 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jan 2016.

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