Trial Title:
64Cu-LNTH-1363S in Patients with Sarcoma or Gastrointestinal Tract Cancer
NCT ID:
NCT06298916
Condition:
Metastatic Sarcoma
Esophageal Cancer
Gastric Cancer
Pancreatic Cancer
Colorectal Cancer
Sarcoma
Conditions: Official terms:
Sarcoma
Gastrointestinal Neoplasms
Conditions: Keywords:
FAPi
Imaging
64Cu-LNTH-1363S
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Intervention model description:
Part 1: Metastatic Sarcoma Part 2: Non-metastatic sarcoma or gastrointestinal tract (GIT)
cancer (esophageal, gastric, pancreatic, colorectal cancer)
Primary purpose:
Diagnostic
Masking:
None (Open Label)
Intervention:
Intervention type:
Combination Product
Intervention name:
64Cu-LNTH-1363S
Description:
64Cu-LNTH-1363S, is a highly selective, high affinity FAP inhibitor (FAPi) that is
radiolabeled with Copper-64 (64Cu) for PET/CT Imaging,
Arm group label:
Experimental Part 1
Arm group label:
Experimental Part 2
Summary:
This is a multicenter, open-label, prospective Phase 1/2a study to assess safety and
tolerability, establish dosimetry and to identify an optimal imaging dose (radioactivity
and mass dose) and imaging time window of 64Cu-LNTH-1363S (64Cu Radiolabeled FAPi PET/CT
Imaging Agent) and to compare its imaging biodistribution with FAP expression by
immunohistochemistry (IHC) in patients with sarcomas or GIT cancers. The study will be
conducted in 2 parts (Part 1 and Part 2).
Detailed description:
Part 1 will determine the biodistribution, dosimetry, optimal dose (radioactivity and
mass dose) and imaging time window of 64Cu-LNTH-1363S in 12 evaluable patients with
supposed FAP-expressing solid tumors (metastatic sarcomas). Two 64Cu-LNTH-1363S mass
doses of ~50 μg and ~90 μg will be studied. Six patients will receive 8 ± 1 millicurie
(mCi) (~50 μg mass dose), followed by another 6 patients will receive 8 ± 1 mCi (~90 μg
mass dose). Two additional radioactivity (6 and 4 mCi) doses will be simulated by
reprocessing raw data from each patient's PET scans.
This study does not involve randomization for dose groups. It will commence with the
lower dose group (~50 μg mass dose). After enrolling 6 evaluable patients in this dose
group, recruitment for the next dose group (~90 μg mass dose) will begin and conclude
upon enrolling 6 evaluable patients. Subsequently, the images will undergo analysis by
blinded central readers.
Part 1 of the study will last approximately 3 weeks for each patient and includes a
Screening Period (up to 14 days), a 1-day Intervention Period, and a Safety Follow-up
Period (7 days post dose).
Part 2 will evaluate 64Cu-LNTH-1363S imaging correlation with FAP expression measured by
IHC (SUVmax and SUVmean vs IHC score) in 20 evaluable patients with non-metastatic,
operable, supposed FAP-expressing solid tumors (sarcomas, esophageal, gastric,
pancreatic, colorectal) planned for surgery within 60 days (from study imaging). If the
optimal radioactivity determined from Part 1 is less than 8 ± 1 mCi, the first 6 patients
in Part 2 will be used to validate this optimal radioactivity. This mean the image
quality scores of the first 6 patients will need to be calculated. If the sum of the
average image quality scores of the 6 patients is higher or equal to 10.5, then the lower
optimal radioactivity determined in Part 1 will be used for the remaining 14 patients,
otherwise the remaining 14 patients in Part 2 will be injected with 8 ± 1 mCi of
64Cu-LNTH-1363S. Part 2 of the study will last approximately 10 to 11 weeks for each
patient and includes: a Screening Period (up to 14 days), a 1-day Intervention Period, a
1-day Safety Follow-up Period (Day 2), and a Scheduled Surgery: IHC Sample Collection
Period (from Day 2 to Day 60).
Both Part 1 and Part 2 of the study will also monitor cardiac safety by detecting changes
in HR, T wave, ST segment and other ECG parameters and look for signals suggesting a
concentration-response relationship of 64Cu-LNTH-1363S for QT and corrected QT interval
(QTc) prolongation.
Criteria for eligibility:
Criteria:
Inclusion Criteria: Part 1
Patients are eligible to be included in the study only if all of the following criteria
apply:
1. Patient must be ≥ 18 years of age and must have provided written informed consent.
2. Patients with suspected FAP-expressing metastatic sarcoma.
3. Patients must have histological, pathological, and/or cytological confirmation of a
metastatic sarcoma (e.g., undifferentiated pleomorphic sarcoma, liposarcoma,
Leiomyosarcoma, myxofibrosarcoma, solitary fibrous tumor, Ewing's sarcoma, synovial
sarcoma, sarcoma not otherwise specified, osteosarcoma).
4. Patients must be willing to consent to provide sufficient and adequate archived
tumor tissue samples (formalin fixed, paraffin embedded sample), preferably from a
biopsy of a tumor lesion obtained either at the time of or after the diagnosis of
disease; if archival tissue sample is unavailable, a new biopsy should be performed
on the most accessible lesion(s) to obtain the tumor tissue sample.
5. Adequate renal function as determined by a calculated creatinine clearance ≥ 60
mL/min (Cockcroft Gault equation).
6. Women of childbearing potential (WOCBP) must have a negative beta-human chorionic
gonadotropin (β-hCG) test and must not be breastfeeding. WOCBP must agree to use a
highly effective method of contraception during the study and for 28 days after the
last injection of the study drug.
7. Male subjects who are able to father a child must agree to avoid impregnating a
partner, to adhere to a highly effective method of contraception and to not donate
sperm during the study and for 28 days after the last injection of the study drug.
Inclusion Criteria: Part 2
1. Patients must be ≥ 18 years of age and must have provided written informed consent.
2. Patients must have histological, pathological, and/or cytological confirmation of a
sarcoma or GIT cancers e.g., esophageal, gastric, pancreatic, colorectal cancer.
3. Patients must have suspected FAP expressing sarcoma or GIT cancers and planned for
surgery within 60 days (from study imaging).
4. Patients must be willing to consent to provide sufficient and adequate tumor tissue
samples (formalin fixed, paraffin embedded sample), from their planned surgery after
participating in study imaging.
5. Adequate renal function as determined by a calculated creatinine clearance ≥ 60
mL/min (Cockcroft Gault equation).
6. Women of childbearing potential (WOCBP) must have a negative beta-human chorionic
gonadotropin (β-hCG) test and must not be breastfeeding. WOCBP must agree to use a
highly effective method of contraception during the study and for 28 days after the
last injection of the study drug.
7. Male subjects who are able to father a child must agree to avoid impregnating a
partner, to adhere to a highly effective method of contraception and to not donate
sperm during the study and for 28 days after the last injection of the study drug.
Exclusion Criteria: Part 1
Patients are excluded from the study if any of the following criteria apply:
1. Unlikely to comply with protocol procedures, restrictions and requirements and
judged by the investigator to be unsuitable for participation.
2. Known pregnancy or breastfeeding.
3. Any PET scan done within 10 physical half-lives of the PET agent prior to receiving
study intervention.
4. They are participating as patients in another clinical study with an Investigational
Product or another systemic therapy administered in the last 3 weeks.
5. Has undergone or plans to undergo PET or single-photon emission computerized
tomography (SPECT) imaging with any other FAPi imaging agent within 6 months prior
to or after participating in this trial.
6. History of QT/QTc interval prolongation, a marked baseline QT/QTc interval
prolongation (e.g., repeated demonstration of a QTc interval, calculated with
Fridericia's correction, > 450 milliseconds) or taking medications known to cause
QT/QTc prolongation.
7. A history of additional risk factors for torsades de pointes (e.g., heart failure,
hypokalemia, family history of long QT syndrome).
8. Have history of QT prolongation or is taking a medication known to cause QT
prolongation.
Exclusion Criteria: Part 2
1. Patients who have received or are scheduled to receive neoadjuvant anti-cancer
therapy.
2. Evidence of metastatic or advanced, inoperable disease.
3. Unlikely to comply with protocol procedures, restrictions and requirements and
judged by the investigator to be unsuitable for participation.
4. Known pregnancy or breastfeeding.
5. Any PET scan done within 10 physical half-lives of the PET agent prior to receiving
study intervention.
6. They are participating as patients in another clinical study with an Investigational
Product or another systemic therapy administered in the last 3 weeks.
7. Has undergone or plans to undergo PET or SPECT imaging with any other FAPi imaging
agent within 6 months prior to or after participating in this trial.
8. History of QT/QTc interval prolongation, a marked baseline QT/QTc interval
prolongation (e.g., repeated demonstration of a QTc interval, calculated with
Fridericia's correction, > 450 milliseconds) or taking medications known to cause
QT/QTc prolongation.
9. A history of additional risk factors for torsades de pointes (e.g., heart failure,
hypokalemia, family history of long QT syndrome)
10. Have history of QT prolongation or is taking a medication known to cause QT
prolongation.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Cincinnati Children's Hospital Medical Center
Address:
City:
Cincinnati
Zip:
45229-3039
Country:
United States
Status:
Recruiting
Contact:
Last name:
Brian Turpin, MD
Phone:
1-513-636-2799
Email:
cancer@cchmc.org
Start date:
November 2024
Completion date:
April 2026
Lead sponsor:
Agency:
Lantheus Medical Imaging
Agency class:
Industry
Source:
Lantheus Medical Imaging
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06298916