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Organoid Based Response Prediction in Esophageal Cancer (RARESTEM/Org)

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ClinicalTrials.gov Identifier: NCT03283527
Recruitment Status : Recruiting
First Posted : September 14, 2017
Last Update Posted : February 15, 2018
Sponsor:
Information provided by (Responsible Party):
John Plukker, University Medical Center Groningen

Brief Summary:

Rationale: Current standard treatment of localized esophageal cancer (EC) with neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy with curative intent results in 30% complete, 40-60% partial and 20% no-response at pathologic examination. Clinical response of nCRT is usually evaluated with PET-CT. However, response measurements are currently still insufficient in optimizing EC treatment. Proper pre-surgical response prediction may allow individualized treatment with esophagus-preservation in complete responders or switching to an alternative treatment in non-responders. Interestingly, in many tumors, a subset of cells has been found to possess cancer stem cell (CSC) properties with associated signaling as drivers of tumor (re-)growth and therapy resistance. Response of CSC-derived tissue resembling in vitro cultured tumor organoids may reflect patient's tumors sensitivity to therapy.

Objective: To create a patient derived organoid model for EC patients to predict the pathologic tumor response to nCRT in clinical practice. This will allow a more personalized approach in future treatment of locally advanced EC.

Study design: Fresh esophageal tumor material will be collected during diagnostic endoscopic ultrasound (EUS) in participating patients. These biopsies will be used to select cancer stem cells, which will be cultured to derive organoids (esophageal cancer patient derived organoids; EC-PDO). When the EC-PDO contain sufficient cells, these cells will be treated with radiotherapy and/or chemotherapy in order to obtain dose-response curves. The response of these EC-PDOs will be compared to the actual tumor response to nCRT treatment in these EC patients, which will be assessed at the definitive pathologic examination of the resection specimen after esophagectomy with curative intent.

Study population: All patients with curatively treatable and resectable esophageal cancer (adenocarcinoma or squamous cell carcinoma) can be included in this trial.

Main study parameters/endpoints: The main endpoint is response prediction to chemoradiotherapy by EC-PDO; the steepness of the dose response survival curve in the organoids in relation to the pathologic response after resection in the clinical situation.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The patients will be asked to undergo 3 to 6 additional biopsies during endoscopic ultrasonography (EUS) for the TNM staging of the tumor. The risk of these additional biopsies is not greater than the biopsies for the diagnosis of EC. The patient will not benefit from participation in this trial.

For the future approach we can get more insight into the mechanism of (chemo)radiation response or resistance to nCRT, which might lead to a better patient selection and more individualized esophageal cancer treatment in the future. This improvement in selection and treatment can result in less over or under-treatment of these EC patients.


Condition or disease
Organoid Esophageal Cancer Chemoradiation

Study Type : Observational
Estimated Enrollment : 100 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Chemoradioresistance in Prospectively Isolated Cancer Stem Cells in Esophageal Cancer-Organoid: RARE STEM-Organoid
Actual Study Start Date : December 1, 2017
Estimated Primary Completion Date : January 1, 2020
Estimated Study Completion Date : January 1, 2020

Resource links provided by the National Library of Medicine





Primary Outcome Measures :
  1. Response prediction by EC-PDO [ Time Frame: january 2020 ]
    The main endpoint is response prediction by EC-PDO; the steepness of the dose response survival curve in relation to the pathologic response after resection.


Secondary Outcome Measures :
  1. EC-PDO growth rate in-vivo [ Time Frame: December 2018- febr 2019 ]
  2. Stem cell characterization measured by the amount of CD24-/CD44+ [ Time Frame: March 2018 ]
  3. Radio/Chemo-sensitivity/resistance; the effective dose 50% (ED50%) of CSCs enriched subpopulation will be compared with the ED50% esophageal cancer cell lines. [ Time Frame: december 2019/january 2020 ]
  4. Clinical response: based on PET-CT (standard): complete, partial or no response [ Time Frame: December 2019/January 2020 ]
  5. Disease free survival (DFS) in months in patients [ Time Frame: December 2020/January 2021 ]
  6. Overall survival (OS) in months [ Time Frame: December 2020/January 2021 ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
All patients with histologically proven adenocarcinoma or squamous cell carcinoma of the esophagus, who are candidates for nCRT followed by resection, can be included in this trial.
Criteria

Inclusion Criteria:

  • Histologically proven adeno- or squamous cell carcinoma of the esophagus
  • Age ≥ 18 years
  • Candidates for curative treatment; clinical stage T1N+/T2-4aN0-3M0
  • Scheduled for endoscopic ultrasound (EUS) procedure for staging and/or treatment purposes
  • Written informed consent

Exclusion Criteria:

  • Patients who are medically unfit for a curative treatment
  • Signs of distant metastases (M1)
  • Patients who are mentally disabled or incapable to give informed consent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03283527


Contacts
Contact: John Plukker, Prof. +315036113684 j.t.m.plukker@umcg.nl
Contact: Kristel Muijs, Dr. +31652724462 c.t.muijs@umcg.nl

Locations
Netherlands
University Medical Center Groningen (UMCG) Recruiting
Groningen, Netherlands, 9713GZ
Contact: John Plukker, Prof.       j.t.m.plukker@umcg.nl   
Contact: Kristrl Muijs, Dr.       c.t.muijs@umcg.nl   
Principal Investigator: John Plukker, Prof         
Martini Ziekenhuis Recruiting
Groningen, Netherlands, 9728NT
Contact: Laurens van der Waaij, Dr.         
Medisch Centrum Leeuwarden Not yet recruiting
Leeuwarden, Netherlands, 8901BR
Contact: Klaas van der Linde, Dr.         
Sponsors and Collaborators
University Medical Center Groningen
Investigators
Principal Investigator: John Plukker, Prof. Surgeon

Responsible Party: John Plukker, Prof.dr., University Medical Center Groningen
ClinicalTrials.gov Identifier: NCT03283527     History of Changes
Other Study ID Numbers: RARESTEM/Organoid
First Posted: September 14, 2017    Key Record Dates
Last Update Posted: February 15, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Esophageal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases