Cancer-Detecting Dye for Oral Cancer

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

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

23 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to test if an investigational dye, called PARPi-FL, can be used to detect this type of cancer. This will be the first time that PARPi-FL is being tried in people. First, the investigators will test the safety of PARPi-FL at different doses to find out what effects, if any, it has on people. The investigators will also see which amount of PARPi-FL is best suited to detect cancers of the mouth and tongue.

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 data supports the idea that Cancer-Detecting Dye for Oral Cancer (also known as: Olaparib, Lynparza) is an effective treatment?

The available research shows that Olaparib, a drug, can effectively reduce the spread and growth of oral cancer cells. In studies using oral cancer cell lines, Olaparib significantly decreased their ability to grow, move, and invade other tissues. In animal tests, it also reduced tumor growth and bone invasion. These results suggest that Olaparib could be a promising treatment for oral cancer by preventing the cancer from spreading and becoming more aggressive. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Olaparib (Lynparza) for oral cancer?

Research shows that Olaparib can reduce the growth and spread of oral cancer cells in lab studies and animal models. It works by blocking certain processes in cancer cells, which helps prevent them from invading other tissues. ^{1 2 3 4 5}

What safety data exists for the cancer-detecting dye treatment?

Olaparib (Lynparza) has been evaluated for safety in various clinical trials, primarily for BRCA-mutated cancers such as ovarian and breast cancer. Safety data from these trials indicate that olaparib is generally well-tolerated, with known side effects documented in studies involving patients with advanced solid tumors, including ovarian cancer. The safety profile has been assessed in multiple studies, including phase I, II, and III trials, focusing on its use as monotherapy and in combination with other treatments. ^{1 2 3 6 7}

Is the cancer-detecting dye, also known as Olaparib or Lynparza, safe for humans?

Olaparib (Lynparza) has been used safely in humans for treating various cancers, including ovarian and breast cancer, and has been approved in several countries. It has been tested in multiple studies, showing it is generally safe for human use, although it is important to discuss potential side effects with a healthcare provider. ^{1 2 3 6 7}

Is the drug Olaparib a promising treatment for oral cancer?

The research does not specifically mention Olaparib as a promising treatment for oral cancer. Instead, it highlights a different approach using a dye called PARPi-FL for better detection of oral cancer. Olaparib is mainly discussed in the context of treating other cancers like ovarian and breast cancer. ^{1 2 8 9 10}

How is the drug Olaparib used in detecting oral cancer different from other treatments?

Olaparib, when used with a cancer-detecting dye, targets the enzyme PARP1 to enhance the detection of oral cancer through optical imaging, which is different from traditional methods that rely on visual examination and biopsies without molecular targeting. ^{1 2 8 9 10}

Research Team

Heiko Schoder, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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.

I am 18 years old or older.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 (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]

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]

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]

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, 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes. [2020]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Olaparib: first global approval. [2020]

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

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

4. England 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. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Possible Action of Olaparib for Preventing Invasion of Oral Squamous Cell Carcinoma In Vitro and In Vivo. [2022]

6. England 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. [2022]

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

Olaparib tablet formulation: effect of food on the pharmacokinetics after oral dosing in patients with advanced solid tumours. [2015]

8. England pubmed.ncbi.nlm.nih.gov

Olaparib for the treatment of breast cancer. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Detection and Delineation of Oral Cancer With a PARP1-Targeted Optical Imaging Agent. [2018]

10. England pubmed.ncbi.nlm.nih.gov

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