PRV211 for Oral Cancer

Recruiting at 4 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Privo Technologies

Must not be taking: Platinum agents

Disqualifiers: Invasive SCC history, Radiotherapy, Chemotherapy, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

40 Participants Needed

Trial Summary

What is the purpose of this trial?

Arm 1 ( Phase 2/3 Run in ): PRV111: Topical Locoregional Delivery Placed Over the Tumor Region Primary Endpoint: Overall Response Rate (ORR) Primary Objective: Demonstrate the safety and efficacy of PRV111 in patients with Carcinoma in Situ (CIS) (WHO 2017) Arm 2 (Phase 1) PRV211: Intraoperative Locoregional Delivery Placed into the Resected Tumor Bed Primary Endpoint: Safety Primary Objective: Determine Safety of PRV211 in intraoperative setting Subject Assignment: Subjects will be assigned to Arm 1 or Arm 2 of this study based on disease staging Arm 1: Pathologically proven and clinically confirmed Tis/CIS of the lip or oral cavity Arm 2: Pathologically proven and clinically confirmed T1-T3, Nx, M0 of the lip or oral cavity

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 treatment PRV211 for oral cancer?

Research shows that intra-arterial chemotherapy with cisplatin, a component of PRV211, can lead to high remission rates and low side effects in oral cancer patients. Additionally, a similar drug, nedaplatin, has been effective in treating advanced oral cancers when combined with radiation therapy. ^{1 2 3 4 5}

Is PRV211 safe for use in humans?

Cisplatin, a component of PRV211, has been used in various treatments for oral cancer and generally shows low side effects when combined with sodium thiosulphate. Most patients experience mild side effects, and severe toxicities are rare, making it generally safe for human use. ^{1 6 7 8 9}

How is the drug PRV211 different from other treatments for oral cancer?

PRV211 is unique because it uses a nanotechnology-based system to deliver cisplatin directly to the tumor site, minimizing systemic side effects and toxicity that are common with traditional chemotherapy. This local delivery method allows for higher concentrations of the drug in the tumor while reducing the risk of harmful side effects throughout the body. ^{1 5 10 11 12}

Eligibility Criteria

Adults over 18 with a specific stage of oral cancer that can be surgically removed are eligible for this trial. They must have an ECOG Performance Status ≤2, indicating they're relatively able to carry out daily activities. Participants must agree to use two forms of birth control and not have any serious medical conditions that would affect their participation.

Inclusion Criteria

My tumor can be removed with surgery.

I am eligible for surgery as a standard treatment.

You are expected to live for at least 6 more months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment (PRV111)

Participants receive PRV111 topical locoregional delivery placed over the tumor region

6-7 months

Minimum 3 treatment visits

Treatment (PRV211)

Participants receive PRV211 intraoperative locoregional delivery placed into the resected tumor bed

1 month post-surgery

Follow-up

Participants are monitored for safety and effectiveness after treatment

12-14 months

Treatment Details

Interventions

• PRV211

Trial Overview The study is testing PRV211, a nano-engineered device delivering chemotherapy directly to the site of tumor removal in oral cancer surgery. The aim is to target any remaining cancer cells locally without affecting the rest of the body. Up to 40 patients will be monitored for safety and effectiveness.

Participant Groups

Group I: Arm 2: Pathologically proven and clinically confirmed T1-T3, Nx, M0 of the lip or oral cavity Experimental Treatment 1 Intervention

Arm 2 PRV211 Intraoperative Locoregional Delivery Placed into the Resected Tumor Bed Primary Endpoint: Safety Primary Objective: Determine Safety of PRV211 in intraoperative setting

Group II: Arm 1: Pathologically proven and clinically confirmed Tis/CIS of the lip or oral cavity Experimental Treatment 1 Intervention

PRV111 Topical Locoregional Delivery Placed Over the Tumor Region Primary Endpoint: Overall Response Rate (ORR) Primary Objective: Demonstrate the safety and efficacy of PRV111 in patients with Carcinoma in Situ (CIS) (WHO 2017)

Who Is Running the Clinical Trial?

Privo Technologies

Lead Sponsor

Trials

2

Recruited

50+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Nedaplatin, a derivative of cisplatin, has shown promising results as an effective anti-tumor agent in advanced recurrent oral cancers when used in combination with radiation therapy.

In two cases treated with this combination, one patient achieved a partial response with tumor regression, while the other experienced a complete response, indicating that this therapy is both safe and effective for advanced oral cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Two cases of recurrent oral cancer responding to radiochemotherapy with selective intra-arterial infusion of nedaplatin]. Yamashita, Y., Kuroda, Y., Yamamoto, T., et al.[2012]

In a study of 55 patients with high-risk oral squamous cell carcinoma, those receiving 100 mg/m2 cisplatin every 3 weeks (arm A) showed better compliance and lower overall toxicity compared to those receiving 40 mg/m2 weekly (arm B).

The three-weekly high-dose cisplatin regimen resulted in significantly fewer severe toxicities, with all grade 4 toxicities occurring in the weekly low-dose group, highlighting a safer treatment option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The comparison between weekly and three-weekly cisplatin delivered concurrently with radiotherapy for patients with postoperative high-risk squamous cell carcinoma of the oral cavity. Tsan, DL., Lin, CY., Kang, CJ., et al.[2021]

In oral squamous cell carcinoma (OSCC), high levels of p22phox were found to contribute to resistance against the chemotherapy drug cisplatin (CDDP), as its knockdown made cancer cells more sensitive to the drug.

Overexpression of p22phox not only prevented CDDP from entering the nucleus, thereby reducing its effectiveness, but also activated the PI3K/Akt pathway, which further diminished CDDP-induced apoptosis, highlighting p22phox as a potential biomarker for CDDP resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

p22phox confers resistance to cisplatin, by blocking its entry into the nucleus. Hung, CC., Chien, CY., Chiang, WF., et al.[2022]

In patients with oral squamous cell carcinoma (OSCC) who were resistant to cisplatin, p22phox was found to be upregulated, suggesting it plays a role in chemotherapy resistance.

Overexpression of p22phox significantly increased resistance to cisplatin and carboplatin, but not to oxaliplatin or 5-fluorouracil, indicating that p22phox could serve as a prognostic biomarker and guide alternative treatment strategies for oral cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential resistance to platinum-based drugs and 5-fluorouracil in p22phox-overexpressing oral squamous cell carcinoma: Implications of alternative treatment strategies. Hung, CC., Chien, CY., Chu, PY., et al.[2018]

Neoadjuvant intraarterial chemotherapy with cisplatin showed high remission rates of 80.6% for regimen A and 67.2% for regimen B in 103 patients with primary squamous cell carcinomas of the oral cavity, indicating its efficacy across all tumor stages.

The treatment demonstrated very low toxicity, particularly in regimen B, and resulted in a survival rate of 79.1% for patients receiving the high-pressure chemo-perfusion, suggesting it is a safe and effective option for managing this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraarterial chemotherapy as neoadjuvant treatment of oral cancer. Kovács, AF., Turowski, B., Ghahremani, MT., et al.[2015]

High concentrations of cisplatin (up to 10 microgram/ml) are necessary to achieve complete antiproliferative effects on oral cancer cells, indicating its potential effectiveness in intraarterial chemotherapy for oral and oropharyngeal cancers.

The study suggests that a sodium thiosulphate to cisplatin ratio of less than 6:1 can be used without significantly reducing the cytotoxic effects of cisplatin, allowing for safer administration of chemotherapy with reduced side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro cytotoxic dose-relation of cisplatin and sodium thiosulphate in human tongue and oesophageal squamous carcinoma cell lines. Kovács, AF., Cinatl, J.[2015]

In a study of 44 patients with stage II-IV oral squamous cell carcinoma, the combination of TS-1 and low-dose cisplatin resulted in a high histological response rate of 61.4%, with a complete response rate of 36.4%.

The treatment was associated with mild toxicities, with severe side effects occurring in only a small percentage of patients, suggesting that this regimen is both effective and safe for use as preoperative chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of a novel oral formation of 5-fluorouracil in combination with low-dose cisplatin as preoperative chemotherapy of oral squamous cell carcinoma. Nakazawa, M., Ohnishi, T., Ohmae, M., et al.[2013]

Chemoembolization using a cisplatin suspension was successfully performed on 103 patients with untreated squamous cell carcinomas of the oral cavity and oropharynx, achieving a 73% overall response rate and 18.5% pathological complete remissions, indicating high efficacy.

The procedure demonstrated low acute systemic toxicity and manageable local complications, suggesting it can be safely used as a neoadjuvant treatment before surgery or radiotherapy, particularly for tumors in the oral tongue and floor of the mouth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemoembolization using cisplatin crystals as neoadjuvant treatment of oral cancer. Kovács, AF.[2013]

In a phase I/II study involving 13 patients with high-risk head and neck squamous cell carcinoma, weekly cisplatin (30 mg/m2) was found to be a safe and tolerable regimen for postoperative chemoradiotherapy, with a high compliance rate of 85%.

The most common acute adverse events were mild, including grade 1-2 anemia (50%), mucositis (43%), and nausea/vomiting (43%), indicating that the treatment was manageable with minimal severe side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Postoperative chemoradiotherapy with weekly cisplatin for patients at high-risk for recurrence of head and neck squamous cell carcinoma-A phase I/II study]. Hanai, N., Suzuki, A., Ozawa, T., et al.[2013]

PRV111, a nanotechnology-based system for local delivery of cisplatin, showed significant efficacy in treating oral cavity squamous cell carcinoma (OCSCC) with a 69% tumor reduction in about 7 days and an 87% response rate in a clinical trial involving patients.

The treatment demonstrated a favorable safety profile, with no dose-limiting toxicities or serious adverse events reported, suggesting that PRV111 could improve patient outcomes while minimizing systemic toxicity associated with traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A nanoengineered topical transmucosal cisplatin delivery system induces anti-tumor response in animal models and patients with oral cancer. Goldberg, M., Manzi, A., Birdi, A., et al.[2023]

Cisplatin-loaded nanoparticles (CDDP-PLA-PEG-NP) effectively target oral carcinoma tissues, showing a 10.36 times higher concentration in tumors compared to standard Cisplatin treatment, based on a study involving 64 golden hamsters.

The nanoparticles demonstrated favorable characteristics, including a size of approximately 143.2 nm and a high drug loading efficiency, indicating their potential as a safe and effective delivery system for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Experimental study of cisplatin loaded polylactic acid-polyethylene glycol nano-particles for targeting oral carcinoma]. Yang, K., Chen, SW., Chen, R., et al.[2018]

In a study of 23 patients with advanced oral squamous cell carcinoma, a two-route cisplatin chemotherapy regimen resulted in an 85.7% objective response rate, with 33.3% achieving a complete response and 52.4% showing partial response.

The treatment was found to be safe, with no severe toxicities reported, and only mild nausea and vomiting observed, indicating that this method could be a promising option for patients with this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The use of two-route Cisplatin chemotherapy in the treatment of oral squamous cell carcinoma]. Li, WS., Wei, SC., Liang, SZ.[2006]

References

1. Japan pubmed.ncbi.nlm.nih.gov

[Two cases of recurrent oral cancer responding to radiochemotherapy with selective intra-arterial infusion of nedaplatin]. [2012]

2. England pubmed.ncbi.nlm.nih.gov

The comparison between weekly and three-weekly cisplatin delivered concurrently with radiotherapy for patients with postoperative high-risk squamous cell carcinoma of the oral cavity. [2021]

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

p22phox confers resistance to cisplatin, by blocking its entry into the nucleus. [2022]

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

Differential resistance to platinum-based drugs and 5-fluorouracil in p22phox-overexpressing oral squamous cell carcinoma: Implications of alternative treatment strategies. [2018]

5. Scotland pubmed.ncbi.nlm.nih.gov

Intraarterial chemotherapy as neoadjuvant treatment of oral cancer. [2015]

6. Scotland pubmed.ncbi.nlm.nih.gov

In vitro cytotoxic dose-relation of cisplatin and sodium thiosulphate in human tongue and oesophageal squamous carcinoma cell lines. [2015]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Phase II study of a novel oral formation of 5-fluorouracil in combination with low-dose cisplatin as preoperative chemotherapy of oral squamous cell carcinoma. [2013]

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

Chemoembolization using cisplatin crystals as neoadjuvant treatment of oral cancer. [2013]

9. Japan pubmed.ncbi.nlm.nih.gov

[Postoperative chemoradiotherapy with weekly cisplatin for patients at high-risk for recurrence of head and neck squamous cell carcinoma-A phase I/II study]. [2013]

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

A nanoengineered topical transmucosal cisplatin delivery system induces anti-tumor response in animal models and patients with oral cancer. [2023]

11. China pubmed.ncbi.nlm.nih.gov

[Experimental study of cisplatin loaded polylactic acid-polyethylene glycol nano-particles for targeting oral carcinoma]. [2018]

12. China pubmed.ncbi.nlm.nih.gov

[The use of two-route Cisplatin chemotherapy in the treatment of oral squamous cell carcinoma]. [2006]