Visualization of Rectal Cancer During Endoscopy, Using a Fluorescent Tracer (RAPIDO-TRACT)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by University Medical Centre Groningen
Sponsor:
Collaborator:
Dutch Cancer Society
Information provided by (Responsible Party):
dr. W.B. Nagengast, MD, University Medical Centre Groningen
ClinicalTrials.gov Identifier:
NCT01972373
First received: October 21, 2013
Last updated: October 24, 2013
Last verified: October 2013
  Purpose

To improve rectal cancer management, there is a need for better visualization of drug targets in rectal cancer to identify patients who might benefit from specific targeted treatments. Molecular imaging of rectal cancer associated targets is a promising technique to accommodate this need. Vascular Endothelial Growth Factor (VEGF), which is differentially expressed in normal versus malignant colon tissue, has proven to be a valid target for molecular imaging. Fluorescent labeling of bevacizumab (a VEGF targeting humanized monoclonal antibody currently used in anti-cancer therapy) using IRDye800CW (a fluorescent dye) has potential advantages in view of safety, infrastructure, costs, stability and imaging resolution. Therefore, the fluorescent tracer bevacizumab-IRDye800CW has been developed at the University Medical Center Groningen (UMCG) and was recently approved to be administered to patients in a tracer dose. To detect this tracer in vivo in patients with colorectal cancer, a newly developed flexible near-infrared (NIR) fluorescence endoscope and optoacoustic endoscope have been developed which can be used in clinical studies. Optical fluorescence imaging may support response evaluation following chemoradiotherapy and give insight which patient might benefit from anti-VEGF targeted therapy in future studies.


Condition Intervention Phase
Rectal Cancer
Drug: Bevacizumab-IRDye800CW
Device: NIR fluorescence endoscopy
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Visualization of a VEGF-targeted Optical Fluorescent Imaging Tracer in Rectal Cancer During Flexible NIR Fluorescence Endoscopy

Resource links provided by NLM:


Further study details as provided by University Medical Centre Groningen:

Primary Outcome Measures:
  • Sensitivity of the marker bevacizumab-IRDye800CW [ Time Frame: First endoscopic procedure before start radio-chemotherapy and second endoscopic procedure 3 weeks after start of radiochemotherapy ] [ Designated as safety issue: No ]

    To determine the sensitivity of the marker bevacizumab-IRDye800CW measured by innovative molecular imaging flexible NIR fluorescence endoscopy, and optionally optoacoustic endoscopy, in identifying target expression and heterogeneity prior to the start, or during early treatment, of neoadjuvant radiochemotherapy, to identify patients who benefit from additional treatment targeting VEGF to increase pCR in future studies.

    Research aim to assess primary objectives by evaluation of biopsy specimen:

    • To assess accumulation of bevacizumab-IRDye800CW in rectal cancer tissue and surrounding tissue at baseline and following radiochemotherapy of patients included in the RAPIDO trial.
    • Evaluation of tumor areas with high fluorescence and low fluorescence signal.
    • To correlate the above to VEGF-levels determined by immuno-histochemistry.


Secondary Outcome Measures:
  • Correlation between bevacizumab-IRDye800CW uptake and pathological response (pCR) [ Time Frame: Endoscopic procedures before and during chemoradiation therapy (after 3 weeks), assesing of pathological respons after churgical intervention ] [ Designated as safety issue: No ]
  • In vivo quantification of the NIR fluorescent signal of bevacizumab-IRDye800CW using the NIR fluorescence endoscope vs. ex vivo VEGF levels in biopsies [ Time Frame: Before start and following chemoradiation therapy (after 3 weeks) ] [ Designated as safety issue: No ]
  • To Perform correlate pathways analyses using RNA/DNA/protein analyses to NIR fluorescence data [ Time Frame: After surgery ] [ Designated as safety issue: No ]
  • The ability of optoacoustic endoscopy to detect bevacizumab-IRDye800CW in deeper areas of the tumor [ Time Frame: Before start en during chemoradiation therapy (after 3 weeks) ] [ Designated as safety issue: No ]
  • Collection of safety regarding administration of Bevacizumab-IRDye800CW [ Time Frame: Participants will be followed the duration of the chemoradiation therapy till surgery ] [ Designated as safety issue: Yes ]
    To abtain information on safety aspectsof the tracer, side effects, adverse events (AE), serious adverse events (SAE) and suspected unexpected serious adverse reactions (SUSAR)


Estimated Enrollment: 30
Study Start Date: October 2013
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: NIR endoscopy with Bevacizumab-IRDye800CW
In this non-randomized, non-blinded, prospective, multicenter feasibility study, bevacizumab-IRDye800CW will be administered to a total of 30 patients with proven locally advanced rectal cancer.
Drug: Bevacizumab-IRDye800CW
Intravenous administration of a microdose (4.5mg, subtherapeutic) of Bevacizumab-IRDye800CW prior to the endoscopic procedure
Other Names:
  • Fluorescence tracer imaging
  • Beva-800CW
  • Bevacizumab-800CW
Device: NIR fluorescence endoscopy
48 hours administration of Bevacizumab-IRDye800CW a flexible NIR fluorescence endoscopy will be performed via the rectum
Other Name: Sigmoid endoscopy using near infrared fluorescence

Detailed Description:

In this non-randomized, non-blinded, prospective, single center feasibility study, patients with locally advanced rectal cancer who are included in the RAPIDO study (NL36315.042.11) will undergo two times epi-illumination endoscopy (in other words flexible NIR fluorescence endoscopy).

The study consists of a total of five study procedure related visits:

  • Visit 1: During a screening visit, eligibility will be evaluated and patient characteristics will be collected.
  • Visit 2: During the second visit 4.5 mg of bevacizumab-IRDye800CW will be administered intravenously. The patient will then be observed for 1 hour post administration.
  • Visit 3: First endoscopy will be performed at baseline (two days after tracer administration); before the start of chemoradiotherapy.
  • Visit 4: 3 weeks after start of the chemotherapy patients will receive a second dose of 4.5 mg of bevacizumab-IRDye800CW (second tracer administration)
  • Visit 5: A second flexible NIR fluorescence endoscopy procedure will be performed (two days after the second tracer injection).

Optionally and when available, we will ask patients if they would like to undergo optoacoustic endoscopy. This is a form of endoscopic ultrasound which is able to detect bevacizumab-IRDye800CW up to 2 cm in depth. The procedure is comparable with NIR fluorescence endoscopy. If patients agree, after removal of the NIR fluorescence endoscope the optoacoustic endoscope will be introduced in the rectum of the patient for detection of bevacizumab-IRDye800CW in deeper areas of the tumor.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Biopsy-proven, newly diagnosed primary rectal adenocarcinoma, i.e. with the lowest part of the tumor less than 16 cm from the anal verge using a rigid rectoscope or flexible endoscope.
  • Locally advanced tumor fulfilling at least one of the following criteria on pelvic MRI indicating high risk of failing locally and/or systemically:

    • Clinical stage (c)T4a
    • cT4b
    • Extramural vascular invasion (EMVI+)
    • N2 i.e. four or more lymph nodes in the mesorectum showing morphological signs on MRI indicating metastatic disease
    • positive mesorectal fascia (MRF), i.e. tumor or lymph node one mm or less from the mesorectal fascia
    • metastatic lateral nodes, > 1 cm (lat Lymph Node+)
  • Staging done within 5 weeks before randomization.
  • No contraindications to chemotherapy, including adequate blood counts:

    • White blood count ≥4.0 x 109/L;
    • Platelet count ≥100 x 109/L;
    • Clinically acceptable haemoglobin levels;
    • Creatinine levels indicating renal clearance of ≥50 ml/min;
    • Bilirubin <35 μmol/l
  • Eastern Cooperative Oncology Group (ECOG) performance score < 1.
  • Patient is considered to be mentally and physically fit for chemotherapy as judged by the medical oncologist.
  • Age ≥ 18 years.
  • Written informed consent.
  • Adequate potential for follow-up.

Exclusion Criteria:

  • Extensive growth into cranial part of the sacrum (above S3) or the lumbosacral nerve roots indicating that surgery will never be possible even if substantial tumour down-sizing is seen.
  • Presence of metastatic disease or recurrent rectal tumour. Familial Adenomatosis Polyposis coli (FAP), Hereditary Non-Polyposis Colorectal Cancer (HNPCC), active Crohn's disease or active ulcerative Colitis.
  • Concomitant malignancies, except for adequately treated basocellular carcinoma of the skin or in situ carcinoma of the cervix uteri. Subjects with prior malignancies must be disease-free for at least 5 years.
  • Known dihydropyrimidine dehydrogenase (DPD) deficiency.
  • Any contraindications to MRI (e.g. patients with pacemakers).
  • Medical or psychiatric conditions that compromise the patient's ability to give informed consent.
  • Concurrent uncontrolled medical conditions.
  • Any investigational treatment for rectal cancer within the past month.
  • Pregnancy or breast feeding.
  • Patients with known malabsorption syndromes or a lack of physical integrity of the upper gastrointestinal tract.
  • Clinically significant (i.e. active) cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac dysrhythmia, e.g. atrial fibrillation, even if controlled with medication) or myocardial infarction within the past 12 months.
  • Patients with symptoms or history of peripheral neuropathy.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01972373

Contacts
Contact: Wouter B Nagengast, MD, PhD +31 (0)50 3615755 w.b.nagengast@umcg.nl
Contact: Jolien JJ Tjalma, MD +31 (0)50 3610030 jjj.tjalma@umcg.nl

Locations
Netherlands
University Medical Centre Groningen Recruiting
Groningen, Netherlands, 9713 GZ
Contact: Wouter B Nagengast, MD, PhD    +3150-3615755    w.b.nagengast@umcg.nl   
Contact: Jolien JJ Tjalma, MD    +3150-3610030    jjj.tjalma@umcg.nl   
Sub-Investigator: Jolien JJ Tjalma, MD         
Sponsors and Collaborators
University Medical Centre Groningen
Dutch Cancer Society
Investigators
Principal Investigator: Wouter B Nagengast, MD, PhD University Medical Centre Groningen
Principal Investigator: Geke AP Hospers, Prof. dr. University Medical Centre Groningen
Principal Investigator: Boudewijn v. Etten, MD, PhD University Medical Centre Groningen
  More Information

No publications provided

Responsible Party: dr. W.B. Nagengast, MD, MD PhD, University Medical Centre Groningen
ClinicalTrials.gov Identifier: NCT01972373     History of Changes
Other Study ID Numbers: NL43407.042.13, 2013-000333-12
Study First Received: October 21, 2013
Last Updated: October 24, 2013
Health Authority: Netherlands: Medical Ethics Review Committee (METC)
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by University Medical Centre Groningen:
VEGF
Fluorescence
Endoscopy
Rectal cancer

Additional relevant MeSH terms:
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 28, 2014