Clinical trial NCT05408871: Non-invasive Measurement of PD-L1 Levels With Positron Emission Tomography (PET) in Head and Neck Malignancies and Intracranial Metastases
Official title: Pilot Study of Non-invasive Measurement of PD-L1 Levels With Positron Emission Tomography (PET) in Head and Neck Malignancies and Intracranial Metastases
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Cancer Head Neck
Metastatic Cancer
Metastatic Lung Cancer
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2022-06-07
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients with head and neck squamous cell carcinoma who plan to undergo tumor resection and lymph node resection (Aim1). Patients with metastases to the brain from melanoma, lung cancer, breast cancer (Aim 2).12 patients with head and neck cancer will be recruited for Aim 1. 12 patients with brain metastases will be recruited for Aim 2.
Primary purpose: DIAGNOSTIC

Brief summary: This study aims to determine the feasibility of non-invasive quantitative PD-L1 measurement using \[a novel PD-L1 positron emission tomography (PET) tracer and perform immunohistochemistry based measurement of PD-L1 levels within resected lesions in head and neck cancer and brain metastases.

Detailed description: This study aims to validate a non-invasive quantitative imaging method of whole tumors using a novel PD-L1 positron emission tomography (PET) tracer in patients with head and neck cancer who undergo resection of primary tumor and locoregional lymph node metastases thus providing an excellent model to perform correlative studies with immunohistochemistry (IHC).

The investigators will extend the study to patients with brain metastases because there is a critical need for a non-invasive test for PD-L1 in this population, as biopsy of these lesions is rare.

In this study, the investigators will image patients with brain metastases, which are predominantly from lung cancer and melanoma, that are planned to undergo biopsy. The ultimate goal of this research is to validate quantitative PD-L1 PET imaging in determining PD-L1 expression within primary and metastatic cancer without the need for biopsy and identify parameters of PD-L1 quantitative PET that will allow its translation into clinical practice. This method can then be used to determine which patients may benefit from immunotherapy.

The primary objective of this study aims to test the difference in non-invasive quantitative PD-L1 PET measures (VT) of lesions between different groups of PD-L1 levels (PD-L1 ≥90% vs \<1%) in head and neck cancer primary lesions.

Secondary objectives:

1. To establish lesion level association between immunohistochemistry measures of PD-L1 levels within primary head and neck cancer lesions (as the outcome) and PD-L1 PET measures (VT);
2. To establish lesion level association between immunohistochemistry measures of PD-L1 levels within locoregional metastases within the neck and resected normal lymph nodes (as the outcome) and PD-L1 PET measures (VT).
3. To establish lesion level association between the degree of tumor inflammatory cell infiltration on IHC in primary head and neck squamous cell carcinoma (SCC) lesions (as the outcome) and PD-L1 PET measures (VT);
4. To establish lesion level association between the degree of tumor inflammatory cell infiltration on IHC in metastatic head and neck SCC lesion (as the outcomes) and PD-L1 PET measures (VT).

Tertiary objective:

To establish lesion level correlation of IHC measures of total/tumor/inflammatory cell PD-L1 levels to PD-L1 (VT) on PET in brain metastases

Eligibility criteria: Inclusion Criteria for Head and Neck Cancer:

* Patients with resectable squamous cell carcinoma of the oropharynx (HPV positive and HPV negative).
* Resectability will be confirmed by a surgical co-investigator.
* If available, HPV-association determined by institutional p16 testing (CINtec antibody demonstrating strong and diffuse nuclear and cytoplasmic staining is at least 70% of cells).
* Absolute neutrophil count (ANC) \> 1500/microliter, absolute lymphocyte count (ALC) \>1000/microliter, hemoglobin \> 9 g/dl, platelets \> 100,000/microliter.
* aspartate aminotransferase (AST) and alanine transaminase (ALT) \< 5 x upper limit of normal. Bilirubin \< 1.5 x upper limit of normal.
* Albumin \> 0 g/dl.
* Creatinine \< 5 x upper limit of normal.
* Women of child-bearing potential must have a negative serum pregnancy test within 7 days prior to treatment

Inclusion Criteria for Brain Metastases:

* Patients with brain metastases
* Tumor size equal or greater than 1 cm
* Resectability or need for laser interstitial thermal therapy (LITT) will be confirmed by a surgical co-investigator.
* Absolute neutrophil count (ANC) \> 1500/microliter, absolute lymphocyte count (ALC) \>1000/microliter, hemoglobin \> 9 g/dl, platelets \> 100,000/microliter
* AST and ALT \< 5 x upper limit of normal. Bilirubin \< 1.5 x upper limit of normal.
* Albumin \> 0 g/dl.
* Creatinine \< 5 x upper limit of normal.
* Women of child-bearing potential must have a negative serum pregnancy test within 7 days prior to treatment

Exclusion Criteria for Head and Neck Cancer:

* Medical contraindication to surgery.
* Full dose anticoagulation.
* Concomitant invasive malignancy, or malignancy within 2 years except for hormonally responsive breast or prostate cancer, resected non-melanoma skin cancer, resected uterine cervical carcinoma.
* Inability to give informed consent.
* Prior systemic therapy, radiation or gross resection for the tumor under study.
* Women may not be pregnant or breast-feeding.
* Receipt of other systemic therapy including investigational agents, radiation or gross resection for treatment of the tumor under study.

Exclusion Criteria for Brain Metastases:

* Medical contraindication to brain surgery.
* Full dose anticoagulation.
* Inability to give informed consent.
* Women may not be pregnant or breast-feeding.

Primary outcomes:
measure: Non-invasive quantitative PD-L1 levels will be measured using PET measures (VT) of lesions for the groups of PD-L1 levels (PD-L1 ≥90% vs <1%, PD-L1 ≥50% vs <1%) in head and neck cancer primary lesions
timeFrame: from with in 2 weeks perioperative up to postoperative
Secondary outcomes:
measure: Immunohistochemistry vs PET measure of PD-L1 levels in head and neck cancer primary lesion
timeFrame: from with in 2 weeks perioperative up to postoperative
measure: Immunohistochemistry vs PET measure of PD-L1 levels in head and neck cancer locoregional neck metastatic lesions and resected normal lymph nodes
timeFrame: from with in 2 weeks perioperative up to postoperative
measure: Immunohistochemistry vs PET measure of infiltrating inflammatory cells in head and neck cancer primary lesion
timeFrame: from with in 2 weeks perioperative up to postoperative
measure: Immunohistochemistry vs PET measure of infiltrating inflammatory cells in head and neck cancer locoregional neck metastatic lesions and resected normal lymph nodes
timeFrame: from with in 2 weeks perioperative up to postoperative
Other outcomes:
measure: Immunohistochemistry vs PET measure of PD-L1 levels within resected brain metastasis tumor cells
timeFrame: from with in 2 weeks perioperative up to postoperative
Locations:
city: New Haven
country: United States
facility: Yale University PET Center
state: Connecticut
Study officials:
affiliation: Yale University
name: Mariam S Aboian, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: