PET Imaging with PARPi for Head and Neck Cancer

Overseen By Ravinder Grewal, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Impaired organ function, Claustrophobia, Allergy to PEG300, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

27 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug 18F-PARPi for head and neck cancer?

The research suggests that 18F-PARPi, a type of PET imaging tracer, may offer greater specificity in detecting head and neck cancer compared to the standard 18F-FDG PET, which can sometimes show false positives due to normal tissue uptake. ^{1 2 3 4 5}

Is PET imaging with 18F-PARPi safe for humans?

A study on PET imaging with 18F-PARPi in patients with head and neck cancer found it to be safe and feasible. Additionally, a phase I study on a similar compound, PARPi-FL, used for oral cancer detection, showed it was safe when applied topically, with no significant side effects observed. ^{1 3 6 7 8}

How does PET imaging with PARPi differ from other treatments for head and neck cancer?

PET imaging with PARPi is unique because it uses a specific tracer, 18F-PARPi, that targets a protein called PARP1, which is involved in DNA repair. This method offers greater specificity compared to the standard 18F-FDG PET imaging, which can be less accurate due to normal tissue uptake, especially after surgery or radiotherapy. ^{1 2 3 5 9}

What is the purpose of this trial?

The purpose of this study is to test the safety of a study drug called PARPi-FL. This drug has been tested in animals but not yet in people. The purpose of this study is to test if a PARPi-FL scan can be used to take pictures of head and neck cancer. The usual approach to imaging this cancer includes several different imaging scans, including x-rays, CT (computed tomography), MRI (magnetic resonance imaging), and PET (positron emission tomography). These tests take pictures of the cancer.

Research Team

Heiko Schöder, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for adults over 18 with Squamous Cell Carcinoma in the oral cavity, oropharynx, or nasopharynx. They should have at least one tumor visible on standard scans that's bigger than 1.5 cm and be scheduled for treatment at MSKCC. Participants need to be fairly active (ECOG status 0-1) and willing to consent.

Inclusion Criteria

Part 1: Scheduled to undergo treatment at MSKCC

Part 1: Willingness to sign informed consent

Part 1: At least one tumor lesion on standard of care imaging with a minimum diameter of at least 1.5 cm

Exclusion Criteria

My creatinine levels are more than twice the upper limit of normal.

My organs are not working well enough to handle certain medications.

Claustrophobia interfering with PET/CT imaging

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I: [18F]-PARPi and PET/CT Scans

Injection of a microdose (< 100 ug) of [18F]-PARPi followed by 3 PET/CT studies to determine biodistribution and kinetics of uptake in squamous cell carcinomas of the head and neck

4 weeks

3 visits (in-person)

Phase II: [18F]-PARPi and PET/CT Scans

Continuation of imaging studies to further assess biodistribution and kinetics in head and neck cancer

4 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging studies

2 years

Treatment Details

Interventions

• [18F]- PARPi

Trial Overview The study is testing a new imaging drug called PARPi-FL in people for the first time, aiming to see if it can effectively image head and neck cancer using PET/CT scans compared to usual methods like x-rays, CT, MRI, and PET alone.

Participant Groups

Group I: Phase II: [18 F]-PARPi and PET/CT Scans Experimental Treatment 2 Interventions

The intervention of this study is the injection of a microdose (\< 10 0 ug) of \[18 F\]- PARPi followed by 3 PET/CT studies to determine the biodistribution of this imaging agent in normal organs as well as the kinetics of uptake in squamous cell carcinomas of the head and neck.

Group II: Phase I: [18 F]-PARPi and PET/CT Scans Experimental Treatment 2 Interventions

The intervention of this study is the injection of a microdose (\< 10 0 ug) of \[18 F\]- PARPi followed by 3 PET/CT studies to determine the biodistribution of this imaging agent in normal organs as well as the kinetics of uptake in squamous cell carcinomas of the head and neck.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Findings from Research

The first-in-human trial of 18F-PARPi for PET imaging in 11 patients with head and neck cancer showed that the tracer was well-tolerated and safe, with no safety concerns reported.

18F-PARPi effectively detected both primary and metastatic lesions, demonstrating higher retention in tumors compared to healthy tissues, indicating its potential as a valuable imaging tool in cancer diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Feasibility of PARP1/2 Imaging with 18F-PARPi in Patients with Head and Neck Cancer. Schöder, H., França, PDS., Nakajima, R., et al.[2021]

18F-FDG PET/CT is a valuable tool in managing head and neck cancers, aiding in staging, treatment planning, and monitoring response to therapy.

The newer 18F-FDG PET/MR imaging combines the detailed soft tissue imaging of MRI with the functional insights from PET, enhancing the overall assessment of head and neck tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PET Imaging for Head and Neck Cancers. Marcus, C., Sheikhbahaei, S., Shivamurthy, VKN., et al.[2021]

The novel PET tracer [18F]PARPi showed significantly higher specificity for detecting tongue tumors compared to the standard [18F]FDG, with a tumor-to-normal tissue ratio of 42.9, indicating its potential for better imaging of head and neck cancers.

In preclinical studies using mouse models, [18F]PARPi allowed for clear differentiation between tumor and healthy tissue, suggesting that it could improve disease staging and monitoring in clinical settings over the current standard of care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluorine-18 labeled poly (ADP-ribose) polymerase1 inhibitor as a potential alternative to 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography in oral cancer imaging. Demétrio de Souza França, P., Roberts, S., Kossatz, S., et al.[2023]

FDG-PET demonstrated a high sensitivity of 96% for detecting lymph node metastases in patients with primary head and neck cancer, outperforming CT and ultrasonography with fine-needle aspiration cytology (US/FNAC).

The use of FDG-PET also revealed second primary tumors in 17% of patients, highlighting its importance in comprehensive cancer assessment and suggesting it should be routinely used in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative evaluation of patients with primary head and neck cancer using dual-head 18fluorodeoxyglucose positron emission tomography. Stokkel, MP., ten Broek, FW., Hordijk, GJ., et al.[2019]

PET imaging is essential for evaluating and managing head and neck squamous cell carcinoma, primarily using [(18)F]fluorodeoxyglucose, but new radiopharmaceuticals are being explored for better biological insights.

Emerging PET tracers like [(18)F]fluoromisonidazole and [(18)F]fluorothymidine can help profile tumors based on characteristics such as hypoxia and tumor repopulation, potentially improving treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Tracers PET in Head and Neck Squamous Cell Carcinoma. Wang, TJ., Menda, Y., Cheng, SK., et al.[2016]

PARP1 is significantly overexpressed in oral squamous cell carcinoma (OSCC) tissues, with levels increasing by approximately 7.8 times compared to normal tissues, making it a promising target for cancer detection.

The fluorescent dye PARPi-FL enables high-contrast imaging of OSCC in vivo, allowing for precise identification of tumors in mouse models, which could improve early detection and surgical outcomes for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection and delineation of oral cancer with a PARP1 targeted optical imaging agent. Kossatz, S., Brand, C., Gutiontov, S., et al.[2018]

The study demonstrated that the topically applied PARPi-FL solution is safe and well-tolerated in 12 patients with oral squamous cell carcinoma, showing no safety concerns during the trial.

PARPi-FL effectively differentiates malignant lesions from surrounding tissue, with the highest fluorescence contrast observed at a dose of 1000 nM, indicating its potential as a rapid, non-invasive tool for early oral cancer diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of a PARP1-targeted topical fluorophore for the detection of oral cancer. Demétrio de Souza França, P., Kossatz, S., Brand, C., et al.[2022]

The imaging agent [(18)F]PARPi effectively targets PARP1 expression in glioblastoma, showing high selectivity with a significant accumulation in tumor tissue compared to healthy brain tissue (1.82% ID/g vs. 0.04% ID/g).

With favorable pharmacokinetic properties and the ability to visualize tumors non-invasively in mouse models, [(18)F]PARPi presents a promising tool for monitoring glioblastoma growth and treatment responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-invasive PET Imaging of PARP1 Expression in Glioblastoma Models. Carney, B., Carlucci, G., Salinas, B., et al.[2019]

In a study of 77 patients with head and neck squamous cell carcinoma, 68Ga-FAPI-04 PET/CT demonstrated superior specificity and accuracy for preoperative N staging compared to 18F-FDG PET/CT, particularly in neck dissection cases.

68Ga-FAPI-04 PET/CT not only detected more distant metastases but also influenced clinical management decisions in 10 out of 61 patients, indicating its potential for improving treatment strategies and monitoring responses to therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The performance of 68Ga-FAPI-04 PET/CT in head and neck squamous cell carcinoma: a prospective comparison with 18F-FDG PET/CT. Jiang, Y., Wen, B., Li, C., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Safety and Feasibility of PARP1/2 Imaging with 18F-PARPi in Patients with Head and Neck Cancer. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

PET Imaging for Head and Neck Cancers. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Fluorine-18 labeled poly (ADP-ribose) polymerase1 inhibitor as a potential alternative to 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography in oral cancer imaging. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Preoperative evaluation of patients with primary head and neck cancer using dual-head 18fluorodeoxyglucose positron emission tomography. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

New Tracers PET in Head and Neck Squamous Cell Carcinoma. [2016]

6. England pubmed.ncbi.nlm.nih.gov

Detection and delineation of oral cancer with a PARP1 targeted optical imaging agent. [2018]

7. Germany pubmed.ncbi.nlm.nih.gov

A phase I study of a PARP1-targeted topical fluorophore for the detection of oral cancer. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Non-invasive PET Imaging of PARP1 Expression in Glioblastoma Models. [2019]

9. Germany pubmed.ncbi.nlm.nih.gov

The performance of 68Ga-FAPI-04 PET/CT in head and neck squamous cell carcinoma: a prospective comparison with 18F-FDG PET/CT. [2023]