Trial Title:
PET-imaging of Two Vartumabs in Patients with Solid Tumors
NCT ID:
NCT06645808
Condition:
Solid Tumor
Colon Carcinoma
Rectal Carcinoma
Osteosarcoma
Chondrosarcoma
Lung Carcinoma
Head and Neck Squamous Cell Carcinoma
Esophageal Carcinoma
Gastric Carcinoma
Pancreas Carcinoma
Bladder Carcinoma
Glioblastoma
Conditions: Official terms:
Carcinoma
Glioblastoma
Squamous Cell Carcinoma of Head and Neck
Osteosarcoma
Esophageal Neoplasms
Chondrosarcoma
Stomach Neoplasms
Urinary Bladder Neoplasms
Pancreatic Neoplasms
Conditions: Keywords:
Basket-trial
Oncology
Study type:
Interventional
Study phase:
Early Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Intervention model description:
Initially, three subjects will be included in the 89Zr-F8scFv cohort, in parallel by
three subjects in the 89Zr-C9scFv cohort (total of 6 patients). Subsequently, an interim
analysis will be conducted to determine the optimal radiation dose and optimal scanning
day for each radiolabeled antibody fragment.
After the interim analysis, cohorts will be expanded by seven more subjects each,
resulting in 20 subjects (2 x 10) total in the initial study across both cohorts. After
completion of the initial study, each cohort may be further expanded by six subjects in
additional indications, totaling (2 x 16) 32 patients. This basket trial aims to include
at least one patient per indication.
For expansion cohort subjects, IMP-administration will occur on day 1, with one PET/CT
scan performed on the most optimal day, either day 1, 2, or 4.
Primary purpose:
Other
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
89Zr-DFO-N-Suc-F8scFv
Description:
89-Zirconium labeled short-chain variable fragment F8 targeting oncofetal CS.
Arm group label:
89Zr-F8scFv
Intervention type:
Biological
Intervention name:
89Zr-DFO-N-Suc-C9scFv
Description:
89-Zirconium labeled short-chain variable fragment C9 targeting oncofetal CS.
Arm group label:
89Zr-C9scFv
Intervention type:
Radiation
Intervention name:
PET/CT scan
Description:
IMP administration will be followed by PET/CT scans on day 1, 2 and 4.
Arm group label:
89Zr-C9scFv
Arm group label:
89Zr-F8scFv
Summary:
VARTUTRACE is a first-in-human PET/CT molecular imaging study in patients with solid
tumors. This study will investigate the biodistribution and pharmacology of two antibody
fragments binding oncofetal Chondroitin Sulfate (CS).
Oncofetal CS are tumor-specific carbohydrate motifs present in proteoglycans and
identified by VAR2 Pharmaceuticals as expressed during fetal development. Oncofetal CS
reappears in the vast majority of cancers while remaining largely absent from normal
tissues.
VAR2 Pharmaceuticals recently developed antibodies specific for oncofetal CS. VARTUTRACE
uses two of these as radiolabeled antibody fragments to study biodistribution, tumor
accumulation, pharmacodynamics and clearance pathways in a diverse patient population.
Detailed description:
VARTUTRACE aims to investigate the biodistribution and pharmacology in patients with
solid tumors of two antibody fragments specific for oncofetal CS.
VAR2 Pharmaceuticals has identified and characterized oncofetal CS as a group of
tumor-specific carbohydrate motifs that appear in placental tissue during fetal
development and in most cancers while remaining largely absent from healthy tissue. VAR2
Pharmaceuticals recently developed a panel of antibodies specific for oncofetal CS and
characterized their tumor specificity, therapeutic, and safety in pre-clinical models
under various formats.
VARTUTRACE is a Phase 0 microdosing study of a single administration of <30 nmol of
one of the two most promising antibody fragments identified by VAR2 Pharmaceuticals - C9
and F8. Both antibody fragments will be used as short chain variable fragments (scFvs)
labelled with the radioisotope Zirconium-89 (89Zr) and are therefore respectively named
89Zr-C9scFv or 89Zr-F8scFv. As it remains unclear from the pre-clinical in vitro and in
vivo data which of the two will have the most optimal tumor targeting properties in
patients with solid tumors, both scFvs will be evaluated.
The biodistribution, pharmacokinetics, pharmacodynamics, and clearance of two of these
antibody fragments is planned to be studied in up to 32 patients with various cancers
(i.e. a basket-trial).
Criteria for eligibility:
Criteria:
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 ≤ 30.0 kg/m2 and weight at least 50 kg and no more than 100 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.
- Serum albumin > 35 g/L.
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. Patients who are considered naïve for treatment for this specific disease: i.e. no
previous chemotherapy, radiotherapy or immunotherapy.
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. Patients who are considered naïve for treatment for this specific disease: i.e. no
previous chemotherapy, radiotherapy or immunotherapy.
4. Patients who are planned for surgical resection of the tumor.
Lung Carcinoma:
1. Patients diagnosed with Non-Small Cell Lung Carcinoma (NSCLC) T1-4N0M0 (stage
I-II-III), according to the 8th edition of the TNM-classification.
2. Histologically or cytologically confirmed diagnosis of NSCLC.
3. Neo-adjuvant treatment according to the standard of care.
4. 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. Patients who are considered naïve for treatment for this specific disease: i.e. no
previous chemotherapy, radiotherapy or immunotherapy.
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. Patients who are considered naïve for treatment for this specific disease: i.e. no
previous chemotherapy, radiotherapy, or immunotherapy.
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. Patients who are considered naïve for treatment for this specific disease: i.e. no
previous chemotherapy, radiotherapy, or immunotherapy.
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. Patients who are considered naïve for treatment for this specific disease: i.e. no
previous chemotherapy or radiotherapy.
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University Medical Center Groningen (UMCG)
Address:
City:
Groningen
Zip:
9713GZ
Country:
Netherlands
Contact:
Last name:
Anne-Fleur Verhaar, MD
Phone:
0031622989025
Email:
anne-fleur@tracercro.com
Contact backup:
Last name:
Noortje van Dijk, Msc
Email:
noortje@tracercro.com
Contact backup:
Last name:
Andor Glaudemans, MD, PhD
Start date:
November 2024
Completion date:
October 2025
Lead sponsor:
Agency:
Var2 Pharmaceuticals
Agency class:
Industry
Collaborator:
Agency:
TRACER Europe BV
Agency class:
Industry
Source:
Var2 Pharmaceuticals
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06645808
