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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test whether a new imaging drug, PARPi-FL, is safe and effective for capturing images of head and neck cancers. The study will evaluate the drug's performance compared to standard imaging methods like x-rays or MRIs. Participants receive a small dose of the drug and undergo PET/CT scans to assess how the cancer absorbs it. Individuals with squamous cell carcinoma in the mouth, throat, or nose who are scheduled for surgery might be suitable for this trial. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer imaging advancements.

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.

Is there any evidence suggesting that this trial's treatment is likely to be safe?

Research has shown that [18F]-PARPi safely images head and neck cancer. Studies have found it effectively identifies cancer sites without major safety concerns. This imaging agent highlights cancer areas during PET/CT scans, providing detailed pictures to help doctors locate the cancer. Trials so far indicate that [18F]-PARPi is well-tolerated, with participants generally not experiencing serious side effects. This is encouraging for those considering joining a trial using this imaging method. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using [18F]-PARPi for head and neck cancer because it presents a novel approach to imaging, rather than traditional treatment. Unlike standard treatments that focus on directly targeting or removing cancer cells, [18F]-PARPi is an imaging agent that helps doctors visualize how the cancer behaves inside the body. This PET imaging technique can provide insights into the biodistribution of the agent within normal organs and its uptake in cancerous tissues, offering a clearer picture of the disease. By understanding the exact dynamics of cancer spread and localization, it could lead to more personalized and effective treatment strategies in the future.

What evidence suggests that this trial's treatment could be effective for head and neck cancer?

Research has shown that [18F]-PARPi PET imaging can capture clear images of head and neck cancers. Studies have found that this imaging agent highlights cancer areas by attaching to PARP enzymes, which are often more active in cancer cells. Early results suggest that [18F]-PARPi is safe and could effectively monitor treatment progress in real-time. The fluorescent version, PARPi-FL, has shown potential in detecting early stages of oral cancers. In this trial, participants will receive [18F]-PARPi to assess its biodistribution and uptake kinetics in squamous cell carcinomas of the head and neck. Although [18F]-PARPi has not yet been tested in humans for this purpose, its method and early animal tests appear promising. ^{1 5 6 7 8}

Who Is on the Research Team?

Heiko Schöder, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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

My cancer is a type of Squamous Cell Carcinoma located in my mouth, throat, or nasal area.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7421489/

Safety and feasibility of PARP1/2 imaging with 18F-PARPi in ... The aim of this study was to determine safety and feasibility of PET imaging with 18 F-PARPi in patients with head and neck cancer.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6764879/

PET Imaging of a [18F]-radiolabeled PARP Inhibitor Monitors ... PET imaging using [ 18 F]PARPi has the potential to be a powerful tool in treatment monitoring by assessing PARP inhibitor target engagement in real-time.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03631017

Imaging With a PET Agent for Detection of Cancers ... 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 ...

4. jnm.snmjournals.org jnm.snmjournals.org/content/60/4/504

PET Imaging of PARP Expression Using 18 F-Olaparib We show that 18 F-olaparib has great potential for noninvasive tumor imaging and monitoring of radiation damage.

5. link.springer.com link.springer.com/article/10.1007/s00259-021-05436-7

Two experts and a newbie: [18F]PARPi vs [18F]FTT ... The fluorescent variant PARPi-FL shows promising clinical data for its use to detect early oral squamous cell carcinomas [28, 29] and was ...

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2018-01908

Fluorine F-18 PARP Inhibitor PET/CT in Diagnosing ... This phase II trial studies the side effects of fluorine F-18 PARP inhibitor in detecting head and neck squamous cell cancer in patients undergoing ...

7. researchgate.net researchgate.net/publication/340421457_Safety_and_Feasibility_of_PARP12_Imaging_with_F-PARPi_in_Patients_with_Head_and_Neck_Cancer

Safety and Feasibility of PARP1/2 Imaging with F-PARPi in ... Conclusions Imaging of head and neck cancer with ¹⁸F-PARPi is feasible and safe. ¹⁸F-PARPi detects primary and metastatic lesions, and retention ...

8. aacrjournals.org aacrjournals.org/clincancerres/article/doi/10.1158/1078-0432.CCR-19-3484/75874/am/Safety-and-feasibility-of-PARP1-2-imaging-with-18F

Safety and feasibility of PARP1/2 imaging with 18F-PARPi in ... Purpose. We performed a first-in-human clinical trial. The aim of this study was to determine safety and feasibility of PET imaging with 18F-PARPi in ...