- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01972373
Visualization of Rectal Cancer During Endoscopy, Using a Fluorescent Tracer (RAPIDO-TRACT)
Visualization of a VEGF-targeted Optical Fluorescent Imaging Tracer in Rectal Cancer During Flexible NIR Fluorescence Endoscopy
Study Overview
Status
Conditions
Intervention / Treatment
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: After chemoradiotherapy 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-three days after the second tracer injection), preferably right before surgery.
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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
-
Groningen, Netherlands, 9713 GZ
- University Medical Centre Groningen
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Diagnostic
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: NIR endoscopy with Bevacizumab-IRDye800CW
In this non-randomized, non-blinded, prospective, feasibility study, bevacizumab-IRDye800CW will be administered to a total of 30 patients with proven locally advanced rectal cancer.
|
Intravenous administration of a microdose (4.5mg, subtherapeutic) of Bevacizumab-IRDye800CW prior to the endoscopic procedure
Other Names:
48-72 hours administration of Bevacizumab-IRDye800CW a flexible NIR fluorescence endoscopy will be performed via the rectum
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
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:
|
First endoscopic procedure before start radio-chemotherapy and second endoscopic procedure 3 weeks after start of radiochemotherapy
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Correlation between bevacizumab-IRDye800CW uptake and pathological response (pCR)
Time Frame: Endoscopic procedures before and after chemoradiation therapy, assesing of pathological respons after churgical intervention
|
Endoscopic procedures before and after chemoradiation therapy, assesing of pathological respons after churgical intervention
|
|
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 after chemoradiation therapy
|
Before start and after chemoradiation therapy
|
|
To Perform correlate pathways analyses using RNA/DNA/protein analyses to NIR fluorescence data
Time Frame: After surgery
|
After surgery
|
|
The ability of optoacoustic endoscopy to detect bevacizumab-IRDye800CW in deeper areas of the tumor
Time Frame: Before start and after chemoradiation therapy
|
Before start and after chemoradiation therapy
|
|
Collection of safety regarding administration of Bevacizumab-IRDye800CW
Time Frame: Participants will be followed the duration of the chemoradiation therapy till surgery
|
To abtain information on safety aspectsof the tracer, side effects, adverse events (AE), serious adverse events (SAE) and suspected unexpected serious adverse reactions (SUSAR)
|
Participants will be followed the duration of the chemoradiation therapy till surgery
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Wouter B Nagengast, MD, PhD, University Medical Center Groningen
- Principal Investigator: Geke AP Hospers, Prof. dr., University Medical Center Groningen
- Principal Investigator: Boudewijn v. Etten, MD, PhD, University Medical Center Groningen
Publications and helpful links
General Publications
- de Jongh SJ, Tjalma JJJ, Koller M, Linssen MD, Vonk J, Dobosz M, Jorritsma-Smit A, Kleibeuker JH, Hospers GAP, Havenga K, Hemmer PHJ, Karrenbeld A, van Dam GM, van Etten B, Nagengast WB. Back-Table Fluorescence-Guided Imaging for Circumferential Resection Margin Evaluation Using Bevacizumab-800CW in Patients with Locally Advanced Rectal Cancer. J Nucl Med. 2020 May;61(5):655-661. doi: 10.2967/jnumed.119.232355. Epub 2019 Oct 18.
- Tjalma JJJ, Koller M, Linssen MD, Hartmans E, de Jongh SJ, Jorritsma-Smit A, Karrenbeld A, de Vries EG, Kleibeuker JH, Pennings JP, Havenga K, Hemmer PH, Hospers GA, van Etten B, Ntziachristos V, van Dam GM, Robinson DJ, Nagengast WB. Quantitative fluorescence endoscopy: an innovative endoscopy approach to evaluate neoadjuvant treatment response in locally advanced rectal cancer. Gut. 2020 Mar;69(3):406-410. doi: 10.1136/gutjnl-2019-319755. Epub 2019 Sep 18. No abstract available.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms
- Neoplasms by Site
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Rectal Diseases
- Colorectal Neoplasms
- Rectal Neoplasms
- Physiological Effects of Drugs
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Bevacizumab
Other Study ID Numbers
- NL43407.042.13
- 2013-000333-12 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Rectal Cancer
-
Ohio State University Comprehensive Cancer CenterNovartis Pharmaceuticals; National Comprehensive Cancer NetworkCompletedStage IIA Rectal Cancer | Stage IIB Rectal Cancer | Stage IIC Rectal Cancer | Stage IIIA Rectal Cancer | Stage IIIB Rectal Cancer | Stage IIIC Rectal Cancer | Recurrent Rectal CancerUnited States
-
M.D. Anderson Cancer CenterRecruitingEvaluation of Quality of Life and Utilities Following Surgical Treatment of Stage I-IV Rectal CancerStage III Rectal Cancer AJCC v8 | Stage IIIA Rectal Cancer AJCC v8 | Stage IIIB Rectal Cancer AJCC v8 | Stage IIIC Rectal Cancer AJCC v8 | Stage IV Rectal Cancer AJCC v8 | Stage IVA Rectal Cancer AJCC v8 | Stage IVB Rectal Cancer AJCC v8 | Stage IVC Rectal Cancer AJCC v8 | Rectal Adenocarcinoma | Stage... and other conditionsUnited States
-
OHSU Knight Cancer InstituteNatera, Inc.RecruitingEstablishing a ctDNA Biomarker to Improve Organ Preserving Strategies in Patients With Rectal CancerStage III Rectal Cancer AJCC v8 | Stage IIIA Rectal Cancer AJCC v8 | Stage IIIB Rectal Cancer AJCC v8 | Stage IIIC Rectal Cancer AJCC v8 | Rectal Adenocarcinoma | Stage IIA Rectal Cancer AJCC v8 | Stage IIB Rectal Cancer AJCC v8 | Stage II Rectal Cancer AJCC v8 | Stage IIC Rectal Cancer AJCC v8United States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)RecruitingStage III Rectal Cancer AJCC v8 | Stage IIIA Rectal Cancer AJCC v8 | Stage IIIB Rectal Cancer AJCC v8 | Stage IIIC Rectal Cancer AJCC v8 | Rectal Adenocarcinoma | Stage IIA Rectal Cancer AJCC v8 | Stage IIB Rectal Cancer AJCC v8 | Stage II Rectal Cancer AJCC v8 | Stage IIC Rectal Cancer AJCC v8United States
-
Roswell Park Cancer InstituteNational Cancer Institute (NCI)WithdrawnStage IIA Rectal Cancer | Stage IIB Rectal Cancer | Stage IIC Rectal Cancer | Stage IIIA Rectal Cancer | Stage IIIB Rectal Cancer | Rectal AdenocarcinomaUnited States
-
OHSU Knight Cancer InstituteOregon Health and Science University; Taiho Pharmaceutical Co., Ltd.RecruitingStage III Rectal Cancer AJCC v8 | Stage IIIA Rectal Cancer AJCC v8 | Stage IIIB Rectal Cancer AJCC v8 | Stage IIIC Rectal Cancer AJCC v8 | Rectal Adenocarcinoma | Stage IIA Rectal Cancer AJCC v8 | Stage IIB Rectal Cancer AJCC v8United States
-
Jonsson Comprehensive Cancer CenterNatera, Inc.; The Joseph Drown FoundationRecruitingStage III Rectal Cancer AJCC v8 | Stage IIIA Rectal Cancer AJCC v8 | Stage IIIB Rectal Cancer AJCC v8 | Stage IIIC Rectal Cancer AJCC v8 | Rectal Adenocarcinoma | Stage IIA Rectal Cancer AJCC v8 | Stage IIB Rectal Cancer AJCC v8 | Stage II Rectal Cancer AJCC v8 | Stage IIC Rectal Cancer AJCC v8 | Locally...United States
-
Case Comprehensive Cancer CenterCompletedStage IIA Rectal Cancer | Stage IIB Rectal Cancer | Stage IIC Rectal Cancer | Stage IIIA Rectal Cancer | Stage IIIB Rectal Cancer | Stage IIIC Rectal Cancer | Stage IIIA Colon Cancer | Stage IIIB Colon Cancer | Stage IIIC Colon Cancer | Recurrent Colon Cancer | Recurrent Rectal Cancer | Stage IVA Colon Cancer | Stage IVA Rectal Cancer and other conditionsUnited States
-
National Cancer Institute (NCI)Active, not recruitingMetastatic Rectal Adenocarcinoma | Rectal Adenocarcinoma | Stage III Rectal Cancer AJCC v7 | Stage IIIA Rectal Cancer AJCC v7 | Stage IIIB Rectal Cancer AJCC v7 | Stage IIIC Rectal Cancer AJCC v7 | Stage IV Rectal Cancer AJCC v7 | Stage IVA Rectal Cancer AJCC v7 | Stage IVB Rectal Cancer AJCC v7 | Locally...United States
-
City of Hope Medical CenterWithdrawnRecurrent Rectal Cancer | Stage I Rectal Cancer | Stage II Rectal Cancer | Stage III Rectal Cancer
Clinical Trials on Bevacizumab-IRDye800CW
-
University Medical Center GroningenRecruiting
-
Deling LiPeking Union Medical College Hospital; Chinese Academy of Sciences; National...Unknown
-
University Medical Center GroningenLeiden University Medical CenterTerminatedPancreatic Cancer | Pancreatic AdenocarcinomaNetherlands
-
University Medical Center GroningenUnknownEndometriosisNetherlands
-
University Medical Center GroningenMartini Hospital GroningenCompleted
-
University Medical Center GroningenActive, not recruitingInverted Papilloma | Molecular Fluorescence ImagingNetherlands
-
University Medical Center GroningenDutch Cancer SocietyEnrolling by invitationSurgery | Thyroid CarcinomaNetherlands
-
University Medical Center GroningenUMC UtrechtCompleted
-
University Medical Center GroningenCompleted
-
University Medical Center GroningenHelmholtz Zentrum MünchenUnknown