Trial of Adoptive T Cell Therapy With Activated P53 Specific T Cells for Treatment of Advanced Colorectal Cancer

NCT02577588 | Terminated Phase 1 DMC

• 1 other identifier: NCT-2009-11-03-1055
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

The study "Phase I trial of Adoptive T cell Therapy with Activated P53 specific T cells for Treatment of Advanced Colorectal Cancer" is an open label, single arm trial.

Conditions

Colorectal Carcinoma

Keywords

p53 Antigen; T cell therapy; autologous; Adoptive Cellular Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Safety

  The primary endpoint is the Dose Limiting Toxicity (DLT), defined as: any adverse event (AE) ≥ Grade 3 according to the Common Terminology Criteria for Adverse Events (CTCAE version 4.03), that is judged by the investigator as definitely, probably or possibly related to the investigational medicinal product (IMP) or to the combination of the IMP and the treatment with FOLFOX 6/Bevacizumab.

  45 days

Secondary Outcomes (1)

• evaluation of p53 specific T cell Responses by analysing data from EliSpot assay

  day 0, 10, 17, 24, 31

Study Arms (1)

re-activated T cells

EXPERIMENTAL

Ten patients with CRC stage UICC IV under routine first line FOLFOX 6/Bevacizumab therapy are planned to receive a singular treatment with an autologous T cell product at a dose of 5x10\^7 (first three or six patients) or 5x10\^8 (last four or seven patients) cells.

Biological: re-activated T cells

Interventions

re-activated T cells BIOLOGICAL

autologous reactivated T cells against p53

Also known as: autologous T cells, p53 activated T cells

re-activated T cells

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed UICC stage IV colorectal cancer and non resectable primary tumor and/or metastases
• Previous palliative standard systemic treatment with FOLFOX, FOLFIRI, or FOLFIRINOX in combination with Bevacizumab or Cetuximab/Panitumumab, and currently under respective treatment
• The following situation after at least four cycles with FOLFOX, FOLFIRI, or FOLFIRINOX in combination with Bevacizumab or Cetuximab/Panitumumab should apply:
• Disease control (stable disease, partial response or complete response) according routine imaging
• Resection of tumor and/or metastases still impossible
• Tolerability of systemic treatment
• The decision of the treating physician is to continue the standard background treatment
• Presence of tumor-reactive T cells in the blood as detected by ex vivo IFN-γ EliSpot assay and classification of the reaction as a response in a blood sample
• ECOG-performance status 0 or 1
• Adequate vein status at both cubital fossas for 16 G puncture (white permanent venous catheter, Braunüle; EN ISO 6009)
• Age ≥ 18 years, any ethnic origin and gender
• Ability of the patient to understand the character and individual consequences of the clinical trial
• Patients should be willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
• Written informed consent (must be available before enrolment in the trial)
• Negative pregnancy test (females of childbearing potential)

You may not qualify if:

• Previous malignancy within the past 5 years. However: Patients who had curatively treated basal cell carcinoma of the skin, early gastrointestinal cancer treated by endoscopic resection and/or in situ carcinoma of the cervix are allowed for enrolment.
• History of organ allograft or prior hematopoetic stem cell transplantation
• History of inflammatory bowel disease (ulcerative colitis, Crohn's disease)
• History of symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], systemic lupus erythematosus, autoimmune vasculitis \[e.g., Wegener's Granulomatosis\])
• History of motor neuropathy considered of autoimmune origin (e.g., Guillain-Barré Syndrome)
• Clinically significant cardiac disease (NYHA Class III or IV).
• Other serious illnesses, which renders the patient unsuitable for study entry or multiple blood sampling
• Serious intercurrent illness, requiring hospitalization
• HIV and/or HBC/HCV positivity, tested by appropriate infection diagnostics during screening period
• Any active infection or signs or symptoms of infection
• Patient pregnant or breastfeeding
• History of hypersensitivity to the investigational medicinal product or to any excipient present in the investigational medicinal product or to anti-coagulance auxiliary medicianal product (Heparin prophylaxis)
• Treatment with immunosuppressive drugs (e.g. systemic corticosteroids) besides intermittent, anti-emetic steroid application during treatment with FOLFOX, FOLFIRI, or FOLFIRINOX in combination with Bevacizumab or Cetuximab/Panitumumab. Topical or inhalation steroids are permitted.
• Treatment with any approved anti-cancer therapy within 28 days prior to enrolment, except the background treatment FOLFOX, FOLFIRI, or FOLFIRINOX in combination with Bevacizumab or Cetuximab/Panitumumab.as recommended by that trial protocol
• Treatment with any live attenuated vaccine within 4 weeks before first administration of investigational medicinal product

Sponsors & Collaborators

• National Center for Tumor Diseases, Heidelberg: lead
• German Cancer Research Center: collaborator
• University Hospital Heidelberg: collaborator

Study Sites (1)

National Center for Tumor desease NCT

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Alexis Ulrich, MD Prof. Dr.

  University Hospital Heidelberg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2015
• First Posted: October 16, 2015
• Study Start: May 1, 2016
• Primary Completion: February 19, 2018
• Study Completion: February 19, 2018
• Last Updated: April 11, 2018

Record last verified: 2018-03

Locations

DE (1)