General
Inclusion Criteria:
1. Willing to adhere to the prohibitions and restrictions specified in this protocol.
2. Capable of giving signed informed consent (voluntarily), indicating that the patient
understands the purpose and procedures required for the study and is willing to
comply with the requirements and restrictions listed in the informed consent form
and in this protocol.
3. Patients aged ≥ 18 years at moment of signing informed consent form.
4. Life expectancy of > 12 weeks.
5. ECOG (Eastern Cooperative Oncology Group) performance status of 0 or 1.
6. BMI ≥ 18.0 and ≤ 35.0 kg/m2 and weight at least 50 kg and no more than 120 kg at
screening.
7. Overtly healthy based on medical history, physical findings, vital signs, ECG at the
time of screening, as judged by the Investigator. Note: one retest of vital
functions and ECG is allowed within the screening window.
8. Adequate liver- and kidney function, defined by the following laboratory results
obtained during screening visit:
- - AST, ALT, and alkaline phosphatase ≤ 2.5x the upper limit of normal (ULN) as
determined by the UMCG laboratory reference values.
- - Serum bilirubin ≤ 2.0x ULN as determined by the UMCG laboratory reference
values.
Patients with known Gilbert disease who have serum bilirubin level ≤ 3x
ULN may be enrolled.
- - INR or APTT ≤ 1.5x ULN as determined by the UMCG laboratory reference values.
This applies only to patients who are not receiving therapeutic
anticoagulation; patients receiving therapeutic anticoagulation should be on a
stable dose.
- - eGFR (based on plasma-creatinine) = >30 mL/min.
9. No other clinically significant laboratory abnormalities as determined by the
investigator. Note: one retest of lab tests is allowed within the screening window.
10. Female patients should be at least 1 year post-menopausal (amenorrhea >12 months
and/or follicle-stimulating hormone >30 mIU/mL) at screening or surgically sterile
(bilateral oophorectomy, hysterectomy, or tubal ligation).
11. Male subjects who are sexually active with a female partner of childbearing
potential must agree to the use of an effective method of birth control, and must
not donate sperm, until 3 months after administration of 89Zr-DFO-N-Suc-scFv (F8 or
C9).
Medical
inclusion Criteria:
Colon Carcinoma:
1. Patients diagnosed with colon carcinoma T1-2-3N0-1M0 (stage I-II-III), according to
the 8th edition of the TNM-classification.
2. Histologically confirmed diagnosis of colon carcinoma.
3. Neo-adjuvant treatment according to the standard of care.
4. Patients who are scheduled for surgical resection of the tumor.
Rectal Carcinoma:
1. Patients diagnosed with rectal carcinoma T1-2-3N0M0 (stage I-II), according to the
8th edition of the TNM-classification.
2. Histologically confirmed diagnosis of rectal carcinoma.
3. Neo-adjuvant treatment according to the standard of care.
4. Patients who are planned for surgical resection of the tumor.
Osteosarcoma:
1. Patients diagnosed with osteosarcoma stage I-IV, according to AJCC staging for Bone
Sarcoma.
2. Histologically confirmed diagnosis of osteosarcoma.
3. Patients who are planned for surgical resection of the tumor.
4. Neo-adjuvant treatment according to the standard of care.
Chondrosarcoma:
1. Patients diagnosed with chondrosarcoma stage I-IV, according to AJCC staging for
Bone Sarcoma.
2. Histologically confirmed diagnosis of chondrosarcoma.
3. Neo-adjuvant treatment according to the standard of care.
4. Patients who are planned for surgical resection of the tumor.
Lung Carcinoma:
1. Anticipated diagnosis of Non-Small Cell Lung Carcinoma (NSCLC) T1-4N0M0 (stage
I-II-III), according to the 8th edition of the TNM-classification, based on imaging
modalities such as (PET)/CT or based on cytology. 2. Neo-adjuvant treatment according to the standard of care.
3. Patients who are planned for surgical resection of the tumor.
Head and Neck Squamous Cell carcinoma (HNSCC):
1. Patients diagnosed with HNSCC of the oral cavity, oropharynx, nasal cavity,
nasopharynx, hypopharynx and larynx.
2. Histologically confirmed diagnosis of HNSCC.
3. Neo-adjuvant treatment according to the standard of care.
4. Patients who are planned for surgical resection of the tumor.
Oesophageal and gastric carcinoma:
1. Patients diagnosed with oesophagus carcinoma T1-3N0-3M0 according to the 7th edition
of the TNM-classification.
2. Patients diagnosed with gastric carcinoma T1-4N0-3M0 according to the 7th edition of
the TNM-classification.
3. Histologically confirmed diagnosis of oesophageal- or gastric carcinoma.
4. Patients who are planned for surgical resection of the tumor.
5. Neo-adjuvant treatment according to the standard of care.
Pancreas carcinoma:
1. Patients diagnosed with pancreas carcinoma T1-3N0-2M0 (stage I, II and III)
according to the 8th edition of the TNM-classification.
2. Histologically or cytologically confirmed diagnosis of pancreas carcinoma.
3. Patients who are planned for surgical resection of the tumor.
4. Neo-adjuvant treatment according to the standard of care.
Bladder carcinoma:
1. Patients diagnosed with invasive bladder carcinoma T2-4aN0M0 according to the 7th
edition of the TNM-classification.
2. Histologically confirmed diagnosis of bladder carcinoma.
3. Patients who are planned for surgical resection of the tumor.
4. Neo-adjuvant treatment according to the standard of care.
Glioblastoma:
1. Anticipated diagnosis of a high-grade glioma (glioblastoma, grade 4 according to the
WHO-classification) based on imaging modalities such as MRI and/or CT or a biopsy.
2. Karnofsky performance status of at least 70%.
3. Neo-adjuvant treatment according to the standard of care.
4. Patients who are planned for surgical resection of the tumor.
General
Exclusion Criteria:
1. Behavioral or cognitive impairment or psychiatric disease that, in the
investigator's opinion, affects the patient's ability to understand and
cooperate with the study protocol.
2. Insufficient venous access for the study procedures.
3. Close affiliation with the investigator, e.g. a close relative of the investigator,
dependent person (e.g. employee or student), employee of the department of surgery
or nuclear department of the UMCG,TRACER or affiliates.
4. Any finding in the medical examinations or medical history giving, in the opinion of
the investigator, reasonable suspicion of a disease or condition that makes
treatment with the investigational drug unadvisable, or that might affect
interpretation of the results of the study or render the patient at high risk for
treatment complications.
5. Participation in an interventional clinical study within 30 days prior to tracer
administration that involved treatment with any drug (excluding vitamins and
minerals) or medical device.
Medical
Exclusion Criteria:
1. The existence of a second concomitant active malignancy or treatment for a second
malignancy within 1 year prior to IMP-administration, except for localized basal or
squamous cell cancer that has been cured at least 90 days before screening.
2. Cardiac impairment with an estimated LVEF <35 % Prolonged QTcF (>450 ms), cardiac
arrhythmias or any clinically significant abnormalities in the resting ECG at the
time of screening, as judged by the investigator.
3. Any abnormalities in the vital signs of the patient, as judged by the investigator,
as a result of which the patient cannot participate. Note: One retest of vital
functions is allowed within the screening window.
4. Any other diseases, metabolic dysfunction, physical examination finding, or clinical
laboratory finding giving reasonable suspicion of a disease or condition that
contraindicates the use of an investigational drug or that may affect the
interpretation of the results or render the patient at high risk from treatment
complications.
5. Major surgical procedure other than for the included diagnosis within four weeks
before IMPadministration. Disease-related procedures, e.g. the placement of a
port-a-cath, placement of a drain,ERCP, are allowed.
6. Current evidence or history of bacterial, viral or fungal infections within 7 days
before 89Zr-DFON-Suc-scFv (F8 or C9) administration as judged by the Investigator.
- - T > 38.0°C or lab confirmed viral/bacterial/fungal infection (PCR) or symptoms
suggestive of an infection)
- Received oral or IV antibiotics within <7 days before administration.
7. Any planned major surgery within the duration of the study (until follow-up visit)
that is not related to the tumor, with the exception of any emergency surgeries.
8. Prior allogeneic bone marrow transplantation or solid organ transplant.
9. A history of anaphylaxis, history of allergic reaction(s), known allergy to one of
the drugs or excipients administered as part of this study. Mild allergies without
angio-edema or treatment need can be acceptable if deemed not of clinical
significance (including allergy to animals or mild seasonal hay fever).
10. Any other diseases, metabolic dysfunction, physical examination finding, or
clinically significant laboratory finding giving reasonable suspicion of a disease
or condition that contraindicates the use of an investigational drug or that may
affect the interpretation of the results or render the patient at high risk from
treatment complications.
