Cancer-Detecting Dye for Oral Cancer

Not currently recruiting at 6 trial locations

Overseen By Heiko Schoder, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: PARP1 inhibitors

Disqualifiers: Recent surgery, Olaparib allergy, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a special dye called PARPi-FL to determine its effectiveness in detecting oral cancer, specifically in the mouth and tongue. Researchers will first assess the dye's safety by administering different doses and observing their effects. They will then determine the optimal amount for cancer detection. This study may suit individuals diagnosed with squamous cell carcinoma of the mouth or throat who are planning surgery. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to advancements in early cancer detection.

Do I have to stop taking my current medications for the trial?

The protocol does not specify if you need to stop taking your current medications. However, if you are currently using a PARP1 inhibitor, you cannot participate in the trial.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently being treated with a PARP1 inhibitor.

What prior data suggests that this dye is safe for detecting oral cancer?

Research shows that the investigational dye, PARPi-FL, is undergoing its first safety tests in humans. Earlier studies used this dye in mice to accurately detect oral cancers, yielding promising results, as the dye was well-tolerated in animals. This trial is in an early phase, focusing on safety and determining the correct dose for humans. While earlier studies provide some evidence of safety, more information is needed to confirm safety in people. Participants in this trial will help researchers understand how well people tolerate the dye and identify any potential side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it uses a fluorescent imaging agent called PARPi-FL to potentially enhance the detection of oral cancers. This dye binds specifically to cancerous cells, making them glow and easier to distinguish from normal tissue during surgery. Unlike traditional imaging methods, which might not clearly differentiate between healthy and cancerous tissue, this approach aims to improve precision in identifying and removing tumors. This could lead to more successful surgeries and better outcomes for patients with oral cancer.

What evidence suggests that this dye is effective for detecting oral cancer?

Research has shown that the investigational dye, PARPi-FL, could aid in detecting oral cancer. In this trial, participants will receive PARPi-FL to assess its effectiveness in highlighting cancerous areas in the mouth. Studies have found that PARPi-FL can make cancerous areas more visible, aiding in treatment. Earlier research used PARPi-FL to identify cancerous spots in the mouth as they occurred, assisting surgeons by distinguishing cancer from normal tissue. PARPi-FL targets a protein called PARP1, often abundant in oral cancer cells, which helps highlight cancerous areas, making them more visible during check-ups or surgeries. ^{2 3 6 7 8}

Who Is on the Research Team?

Heiko Schoder, 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 mouth or throat, who are scheduled for surgery and have not had recent oral surgery. They must be able to perform daily activities with little to no assistance (ECOG status 0-1) and cannot have had prior treatment with PARP inhibitors.

Inclusion Criteria

I am fully active or can carry out light work.

My cancer is at any stage but has not spread to distant organs.

My cancer is a type of squamous cell carcinoma located in my mouth or throat.

Exclusion Criteria

I am currently taking or have taken a PARP1 inhibitor.

Known hypersensitivity to PEG Eligibility criteria will be assessed by an experienced oral surgeon, typically the Co-PI of the study.

Known hypersensitivity to Olaparib

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Treatment

Increasing concentrations of PARPi-FL are used in up to 12 patients to determine the optimal concentration for imaging.

4-6 weeks

Multiple visits for dose escalation and imaging

Phase II Treatment

The optimal concentration of PARPi-FL determined in Phase I is used to image 18 patients on the day of surgery.

1 day

1 visit (in-person, day of surgery)

Follow-up

Participants are monitored for safety and effectiveness after treatment, correlating imaging findings with histopathologic findings.

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Olaparib

Trial Overview The study is testing a new dye called PARPi-FL to see if it can help detect cancer in the tongue and mouth. Participants will receive varying doses of this investigational dye to determine its safety and the optimal amount needed for cancer detection.

How Is the Trial Designed?

Group I: Fluorescent PARPi Binding Imaging Agent PARPi-FL Experimental Treatment 1 Intervention

In the phase I of the study, increasing concentrations of PARPi-FL will be used in up to 12 patients with OSCC to determine concentration that results in the highest contrast between tumor and normal mucosa. Dose escalation will be performed in groups of three patients until image contrast decreases, side effects are noted or the concentration of PARPi-FL exceeds 1μM. Imaging will be performed in the Department of Surgery during a presurgical visit including clinical examination of the oral cavity. In the phase II part of the study the concentration of PARPi-FL determined in phase I will be used to image 18 patients with OSCC on the day of surgery. Imaging findings will be correlated with histopathologic findings in the surgically resected specimens.

Olaparib is already approved in European Union, United States for the following indications:

Approved in European Union as Lynparza for:

• Breast cancer
• Ovarian cancer
• Fallopian tube cancer
• Peritoneal cancer
• Pancreatic cancer
• Prostate cancer
• Endometrial cancer

Approved in United States as Lynparza for:

• Ovarian, fallopian tube, and primary peritoneal cancer
• Breast cancer
• Prostate cancer
• Pancreatic cancer

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

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]

Olaparib is an oral medication that inhibits poly (ADP-ribose) polymerase and is primarily developed for treating BRCA mutation-positive ovarian cancer, with its capsule formulation already approved in the EU and USA.

The drug is currently undergoing extensive clinical trials for various cancers, including breast, gastric, and pancreatic cancers, indicating its potential broad application in oncology beyond ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib: first global approval. Deeks, ED.[2020]

Olaparib, a PARP inhibitor, has shown significant clinical benefits in improving progression-free survival for patients with BRCA1 or BRCA2 mutated HER2 negative metastatic breast cancer compared to standard chemotherapy.

The drug has a manageable safety profile, making it a promising treatment option, particularly for triple negative breast cancer, although further research is needed to optimize its use with other therapies and identify suitable biomarkers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib for the treatment of breast cancer. Griguolo, G., Dieci, MV., Guarneri, V., et al.[2019]

PARPi-FL, a fluorescently labeled small-molecule inhibitor targeting the DNA repair enzyme PARP1, is being evaluated in a clinical trial as a potential diagnostic tool for improving the detection and delineation of oral cancer.

This molecularly targeted imaging approach aims to enhance the specificity and sensitivity of oral cancer detection compared to traditional methods, which rely heavily on visual examination and histopathology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection and Delineation of Oral Cancer With a PARP1-Targeted Optical Imaging Agent. Kossatz, S., Weber, W., Reiner, T.[2018]

Olaparib is particularly effective for patients with BRCA-mutated ovarian cancer, but it also benefits a subset of patients with BRCA wild-type tumors that have loss-of-function mutations in DNA repair genes, showing similar treatment outcomes.

The study suggests that patients with specific HRR gene mutations, even without BRCA mutations, can be identified as a group that may respond well to olaparib, indicating a potential for broader use of this treatment in ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes. Hodgson, DR., Dougherty, BA., Lai, Z., et al.[2020]

Olaparib, a PARP1 inhibitor, significantly reduced the proliferation, migration, invasion, and adhesion of oral cancer cells in vitro, indicating its potential as a therapeutic agent against oral carcinoma.

In vivo studies showed that olaparib inhibited tumor growth and bone invasion in mice, associated with changes in key proteins related to tumor progression and epithelial-mesenchymal transition (EMT), suggesting it could be an effective strategy for preventing recurrence and metastasis in oral cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Possible Action of Olaparib for Preventing Invasion of Oral Squamous Cell Carcinoma In Vitro and In Vivo. Nakamura, N., Fujihara, H., Kawaguchi, K., et al.[2022]

In a Phase I study involving 60 patients, it was found that taking olaparib with food slows its absorption rate, delaying peak plasma levels by about 2.5 hours and reducing peak exposure by approximately 21%.

Despite the slower absorption when taken with food, the overall extent of olaparib absorption remained unchanged, indicating that patients can still achieve effective drug levels even with dietary considerations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib tablet formulation: effect of food on the pharmacokinetics after oral dosing in patients with advanced solid tumours. Plummer, R., Swaisland, H., Leunen, K., et al.[2015]

Olaparib, a PARP inhibitor, showed a 36% objective response rate in women with relapsed ovarian cancer and a germline BRCA1/2 mutation, even after they had undergone multiple lines of chemotherapy, indicating its efficacy in this challenging patient population.

The median duration of response to olaparib was 7.4 months, and the safety profile was consistent across patients who had received three or more lines of prior chemotherapy, with similar rates of serious adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety. Matulonis, UA., Penson, RT., Domchek, SM., et al.[2022]

Olaparib (Lynparza) is approved for treating adult patients with high-risk early breast cancer that has a germline BRCA mutation, following chemotherapy treatment.

This approval highlights Olaparib's role as an adjuvant therapy, which means it is used after initial treatments to help prevent cancer recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Adjuvant Treatment for High-Risk Early Breast Cancer. Aschenbrenner, DS.[2022]

In a phase I study involving 12 patients with advanced solid tumors, the combination of olaparib and bevacizumab was found to be generally well tolerated, with no dose-limiting toxicities reported.

The most common side effects were mild nausea and fatigue, indicating that the treatment has an acceptable safety profile, making it a candidate for further clinical investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study to assess the safety and tolerability of olaparib in combination with bevacizumab in patients with advanced solid tumours. Dean, E., Middleton, MR., Pwint, T., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9447371/

A Phase I Study of a PARP1-targeted Topical Fluorophore for ... We explored the use of a fluorescent imaging agent, PARPi-FL (20–24), as a tool for non-invasive in vivo identification of malignant oral lesions in real time ( ...

2. nature.com nature.com/articles/srep21371

Detection and delineation of oral cancer with a PARP1 ... Our results suggest that PARP1 imaging with PARPi-FL can enhance the detection of oral cancer, serve as a screening tool and help to guide surgical resections.

3. jnm.snmjournals.org jnm.snmjournals.org/content/early/2025/06/12/jnumed.124.269428

Translational Potential of Fluorescent PARP1 Inhibitor as a ... PARPi-FL is being evaluated in a phase 1/2 trial for detecting oral squamous cell carcinoma, though application time in the oral cavity is 2 min ...

4. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0147752

Optical Imaging of PARP1 in Response to Radiation in Oral ... We show that PARP1 expression in oral cancer is high, and that the uptake of PARPi-FL is selective, irrespective of whether cells were exposed to irradiation or ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7136849/

Validation of the use of a fluorescent PARP1 inhibitor for the ... In oral cancer, we developed a staining and imaging method for freshly excised biopsies that allows for the identification of positive margins within minutes ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03085147

A Dye for the Detection of Cancer of the Tongue and Mouth The investigators will also see which amount of PARPi-FL is best suited to detect cancers of the mouth and tongue. Official Title. A Phase I/II Study of the ...

7. medchemexpress.com medchemexpress.com/parpi-fl.html?srsltid=AfmBOoqE1AQtvavHjw5P7UGUSjIyFC4iKmSjrJ2fHPVl0cKHCEwOiMVd

PARPi-FL (Olaparib-bodipy FL) | PARP1 Inhibitor PARPi-FL (75 nmol; intravenous injection; single dose) enables high-contrast imaging of tumors in a mouse model of oral squamous cell carcinoma, and the signal ...

8. medrxiv.org medrxiv.org/content/10.1101/2020.11.09.20228536v1.full

A Phase I Study of a PARP1-targeted Topical Fluorophore ... Here, we present results from a phase I safety and feasibility study on fluorescent, topically applied PARPi-FL. Patients and Methods Twelve ...