Visualization of Rectal Cancer During Endoscopy, Using a Fluorescent Tracer

NCT ID: NCT01972373

Last Updated: 2024-04-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-31
• Study Completion Date: 2017-01-31

Brief Summary

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.

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.

Conditions

Rectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Bevacizumab-IRDye800CW

Intervention Type: DRUG

Intravenous administration of a microdose (4.5mg, subtherapeutic) of Bevacizumab-IRDye800CW prior to the endoscopic procedure

NIR fluorescence endoscopy

Intervention Type: DEVICE

48-72 hours administration of Bevacizumab-IRDye800CW a flexible NIR fluorescence endoscopy will be performed via the rectum

Interventions

Bevacizumab-IRDye800CW

Intravenous administration of a microdose (4.5mg, subtherapeutic) of Bevacizumab-IRDye800CW prior to the endoscopic procedure

Intervention Type: DRUG

NIR fluorescence endoscopy

48-72 hours administration of Bevacizumab-IRDye800CW a flexible NIR fluorescence endoscopy will be performed via the rectum

Intervention Type: DEVICE

Other Intervention Names

Fluorescence tracer imaging; Beva-800CW; Bevacizumab-800CW; Sigmoid endoscopy using near infrared fluorescence

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Dutch Cancer Society

OTHER

Sponsor Role: collaborator

University Medical Center Groningen

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Wouter B Nagengast, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Groningen

Geke AP Hospers, Prof. dr.

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Groningen

Boudewijn v. Etten, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Groningen

Locations

University Medical Centre Groningen

Groningen, , Netherlands

Countries

Netherlands

References

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.

Reference Type: DERIVED

PMID: 31628218 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31533965 (View on PubMed)

Other Identifiers

2013-000333-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NL43407.042.13

Identifier Type: -

Identifier Source: org_study_id