Small Cell Lung Carcinoma (SCLC)
Conditions
Keywords
Small Cell Lung Carcinoma (SCLC), [68Ga]Ga-PentixaFor, immunohistochemistry (IHC), CXCR4 expression, [18F]FDG, Safety
Brief summary
\[68Ga\]Ga-PentixaFor PET-CT will be performed in patients with Small cell lung cancer (SCLC) to confirm the targeting of CXCR4 by \[68Ga\]Ga-PentixaFor
Detailed description
Small cell lung cancer (SCLC) accounts for approximately 15% of lung cancers, but remains a cancer with a poor prognosis, often detected at a metastatic stage and associated with a high rate of early recurrence. Therapeutic options for unresectable SCLC are limited and essentially rely on first-line radiochemotherapy for limited disease or chemo-immunotherapy, possibly supplemented by radiotherapy, for extensive disease. CXCR4 is a chemokine receptor that is highly expressed in this cancer. By targeting CXCR4 with \[177Lu\]Lu-PentixaTher or \[90Y\]Y-PentixaTher, patients with SCLC could benefit from a new type of treatment in this indication: Peptide Receptor Radionuclide Therapy (PRRT). However, there is a need for a preliminary diagnostic study due to a lack of published data. \[68Ga\]Ga-PentixaFor is an experimental compound that binds with high affinity to CXCR4 and appears to be a promising candidate for PET-CT imaging of SCLC. This initial step is crucial to confirm CXCR4 targeting by \[68Ga\]Ga-PentixaFor before considering PRRT with therapeutic radionuclides such as Lu-177 or Y-90 in future trials.
Interventions
\[68Ga\]Ga-PentixaFor PET-CT
Sponsors
Institut Cancerologie de l'Ouest
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Written informed consent signed before performing any trial specific procedure. 2. Male or female, age ≥ 18 years at time of study entry. 3. Patient with histologically proven small cell lung carcinoma, inoperable, non-pre-treated. 4. Metastatic disease documented by conventional imaging and/or \[18F\]FDG PET-CT with at least one metastatic measurable lesion (RECIST 1.1). Patients eligible for 1st line metastatic treatment. 5. Availability of tissue material (primary lesion and/or metastatic site) to allow additional immunohistochemical studies. 6. PS \< 2. 7. Consent to use a contraception method for at least 3 months after each administration of \[68Ga\]Ga-PentixaFor. 8. Adequate Organ function confirmed by laboratory test results allowing for safe the \[68Ga\]Ga-PentixaFor administration. 9. Life expectancy greater than 3 months. 10. Patient has valid health insurance. 11. Patient willing and able to comply with the protocol throughout the duration of the study, including during treatment and scheduled visits and examinations, including follow-up.
Exclusion criteria
1. History of cancer in the 3 years prior to entry into the trial other than basal cell carcinoma of the skin or carcinoma in situ of the cervix. 2. History of anti-cancer treatments such as chemotherapy, radiotherapy or immunotherapy as well as other clinical trials for SCLC before the first \[68Ga\]Ga-PentixaFor PET-CT imaging. 3. Inability to lie still for at least 1 hour, or known claustrophobia. 4. Serious non-malignant disease (e.g., psychiatric, infectious, autoimmune, or metabolic) which may interfere with study objectives or patient safety or compliance, in the judgment of the investigator. 5. Unstable diabetes with blood glucose \> 2 g/L. 6. Known hypersensitivity to any active pharmaceutical agent or constituent of the \[68Ga\]Ga-PentixaFor and/or \[18F\]FDG product. 7. Body weight of less than 48 kg. 8. Mental impairment that may compromise the ability to give informed consent and comply with study requirements. 9. Pregnant, likely to be pregnant or breastfeeding woman. 10. Patient deprived of liberty, under judicial safeguard, under curatorship or placed under the authority of a guardian. 11. Disorder preventing understanding of trial information or informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the concordance of tumoral lesions detected between [68Ga]Ga-PentixaFor PET-CT and [18F]FDG PET-CT, considered as the reference, performed at diagnosis | 30 days | The concordance between the two techniques (\[18F\]FDG PET-CT and \[68Ga\]Ga-PentixaFor PET-CT) will be assessed by lesion at diagnosis. Cohen's Kappa coefficient will be calculated and accompanied by the probability of finding the same lesion on \[68Ga\]Ga-PentixaFor PET-CT knowing that it was present on \[18F\]FDG PET-CT (which may be similar to a measurement of sensitivity). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the diagnostic performances of [68Ga]Ga-PentixaFor PET-CT compared to [18F]FDG PET-CT considered as the reference. | 24 months | The diagnostic performances will be assessed using the Specificity, at diagnosis time on one hand, and at disease progression time on the other hand. |
| Evaluate the correlation between semi-quantitative data of [68Ga]Ga-PentixaFor PET-CT with CXCR4 expression on biopsies, assessed by immunohistochemistry (IHC). | 24 months | The correlation between the standardized uptake values (SUV) of \[68Ga\]Ga-PentixaFor -positive lesions and the biological expression of CXCR4 will be described by Spearman's ρ, at diagnosis and at disease progression time if data are available. |
| Describe the lesions identified by [68Ga]Ga-PentixaFor PET-CT and by [18F]FDG PET-CT. | 24 months | The qualitative analysis will focus on lesion description in each major organ (lung, lymph node, bone marrow, brain...). Quantitative analysis will focus on continuous parameters at the lesion level (SUV, MTV, TLG and tumour-to-background ratio, etc.). The detection rate of tumour lesions will be calculated. This analysis will be conducted for each radiotracer at diagnosis time on one hand, and at disease progression time on the other hand. |
| Evaluate the concordance of tumoral lesions detected between [68Ga]Ga-PentixaFor PET-CT and [18F]FDG PET-CT, considered as the reference, performed at disease progression. | 24 months | The concordance between the two techniques (\[18F\]FDG PET-CT and \[68Ga\]Ga-PentixaFor PET-CT) will be assessed by lesion at disease progression. Cohen's Kappa coefficient will be calculated and accompanied by the probability of finding the same lesion on \[68Ga\]Ga-PentixaFor PET-CT knowing that it was present on \[18F\]FDG PET-CT (which may be similar to a measurement of sensitivity). |
| Description of the evolution of [68Ga]Ga-PentixaFor PET-CT data obtained at diagnosis and at disease progression time at the patient level. | 24 months | Description of \[68Ga\]Ga-PentixaFor PET-CT data between diagnosis and disease progression time at the patient level will focus on the evolution of SUV value for each patient. |
| Assess safety profile of [68Ga]Ga-PentixaFor. | 24 months | The occurrence and the frequency of adverse events of \[68Ga\]Ga-PentixaFor will be assessed up to 48 hours after \[68Ga\]Ga-PentixaFor administration. The safety is assessed using the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 5.0. |
| Compare the number of lesions detected by [18F]FDG PET-CT and those detected by [68Ga]Ga-PentixaFor PET-CT. | 24 months | A comparison of all lesions number detected between the two radiotracers will be conducted at diagnosis time on one hand, and at disease progression time on the other hand. |
Countries
France
Contacts
Primary ContactMarie LACOMBE, MD
Backup ContactNadia ALLAM, PhD
Outcome results
None listed