PRV211 for Oral Cancer
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2 & 3
Recruiting
Sponsor: Privo Technologies
Must not be taking: Platinum agents
Disqualifiers: Invasive SCC history, Radiotherapy, Chemotherapy, others
No Placebo Group
Prior Safety Data
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.
12345Is 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.
16789How 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.
15101112Eligibility 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.
+7 more
Trial 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Group I: Arm 2: Pathologically proven and clinically confirmed T1-T3, Nx, M0 of the lip or oral cavityExperimental Treatment1 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 cavityExperimental Treatment1 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)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
The University of ChicagoChicago, IL
Advanced ENT and AllergyLouisville, KY
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Who Is Running the Clinical Trial?
Privo TechnologiesLead Sponsor
National Cancer Institute (NCI)Collaborator
References
[Two cases of recurrent oral cancer responding to radiochemotherapy with selective intra-arterial infusion of nedaplatin]. [2012]Nedaplatin, a cisplatin derivative, has been reported to be an effective anti-tumor agent for head and neck cancer. We experienced two patients with advanced recurrent oral cancers who received combination therapy of intra-arterial nedaplatin infusion and radiation therapy, and tumoricidal effects were obtained in these cases. At the end of 3 courses, a partial response(PR)was obtained with regression of the tumor in the first case, and FDGPET showed a complete regression of recurrent tumor for a complete response(CR)in another case. This combination therapy is quite safe and effective for the treatment of advanced oral cancers.
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]The aim of this study was to compare the outcomes of postoperative adjuvant concomitant chemoradiotherapy using two different schedules of cisplatin for patients with high-risk oral squamous cell carcinoma (OSCC).
p22phox confers resistance to cisplatin, by blocking its entry into the nucleus. [2022]Cisplatin (CDDP) is a potent chemotherapeutic agent but resistance to the drug remains a major challenge in cancer treatment. To evaluate the efficacy of CDDP in oral squamous cell carcinoma (OSCC), we found that p22phox was highly expressed in CDDP-resistant OSCC specimens. Knockdown of p22phox sensitized OSCC cell lines to CDDP (P
Differential resistance to platinum-based drugs and 5-fluorouracil in p22phox-overexpressing oral squamous cell carcinoma: Implications of alternative treatment strategies. [2018]We have previously shown that p22phox confers resistance to cisplatin in oral squamous cell carcinoma (OSCC). Whether p22phox has clinical correlation with cisplatin resistance and affects the efficacy of other platinum or nonplatinum drugs is unknown.
Intraarterial chemotherapy as neoadjuvant treatment of oral cancer. [2015]Neoadjuvant chemotherapy in patients with primary squamous cell carcinomas of the oral cavity should lead to high remission rates whilst having low morbidity. Efficacy can also be enhanced by treating small tumour stages. As part of a multi-modality therapy of all stages of primary oral cavity carcinoma, 103 patients were treated with neoadjuvant intraarterial (i.a.) chemotherapy. After regimen A with 100 mg/m2 i.a. cisplatin followed by 5 day continuous intravenous infusion of 5-fluorouracil (1 g/m2 per day) in 36 patients, an i.a. high pressure chemo-perfusion with a dose of 150 mg/m2 cisplatin was used with simultaneous intravenous infusion of 9 g/m2 sodium thiosulfate (regimen B, 67 patients). Subsequent treatment comprised radical surgery and simultaneous radiochemotherapy with docetaxel. Partial and complete remissions were found in 80.6% (regimen A) and 67.2% (regimen B) of cases, tumour growth was inhibited in 11.1% and 31.3%. Very low toxicity could be shown especially in regimen B. 66.7% and 74.6% of patients could be operated on radically. Survival rate was 61.1% (regimen A, 22.7 months of mean observation time) and 79.1% (regimen B, 8.4 months). Patients with high-grade remissions seemed to have a survival advantage. Neoadjuvant i.a. chemotherapy with cisplatin, especially in its high dose variant, is a practical therapeutic tool for the treatment of all stages of primary oral cavity carcinoma.
In vitro cytotoxic dose-relation of cisplatin and sodium thiosulphate in human tongue and oesophageal squamous carcinoma cell lines. [2015]Intraarterial chemotherapy of oral and oropharyngeal cancer with cisplatin (cis-diamminedichloroplatinum [II]) has experienced a revival in the last decade. Side-effects of the therapy were very low with concomitant systemic infusion of the neutralizing agent sodium thiosulphate. The requisite dose of the chemotherapeutic agent which safely leads to apoptosis of oral cancer cells has not yet been assessed in vitro, nor has the combination of cisplatin and sodium thiosulphate been examined for the potential reduction of cytotoxicity in oral cancer cells.
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]TS-1 is a novel oral 5-fluorouracil containing tegaful (prodrug of 5-FU) and two biochemical modulators. These modulators feature effect-enhancing and adverse reaction-reducing activity. We investigated the histological response and toxicities of combination chemotherapy with TS- 1 and low-dose cisplatin and evaluated its usefulness as preoperative chemotherapy Forty-four newly diagnosed patients with stage Il-IV oral squamous cell carcinoma were enrolled in this study from February 2002 to April 2004. Patients were administered TS-1 80 mg/m2/day (days 1-14) and cisplatin 5 mg/m2/day (days 1-5 and 8-12) followed by radical surgery within 2 weeks. The histopathological effect of chemotherapy, which was a surrogate endpoint of this trial, was evaluated with surgical or biopsy specimens. The rate of histological antitumor effect was as follows: complete response (CR) 36.4%, partial response (PR) 25.0%, minor response (MR) 18.1% and no change (NC) 20.5%. The rate of histological response (CR + PR) was 61.4%. The CR rate of effective cases was 59.3%. The main toxicities occurred in bone marrow and the digestive tract. The incidence of severe toxicity such as grade 3 or 4 was 4.5% in anemia, 9% in leukocytopenia, 11.4% in neutropenia, 4.5% in thrombocytopenia and 2.3% in anorexia, diarrhea and urticaria. Most patients showed no toxicity or mild toxicities. TS- 1 with low-dose cisplatin has highly effective antitumor activity and mild toxicities. In particular, the CR rate was very high. It is suggested that this regimen is suitable for neoadjuvant chemotherapy. We expect that this chemotherapy will contribute to avoidance of surgery for small tumors (stages I and II) and will enable function-preserving surgery for advanced tumors.
Chemoembolization using cisplatin crystals as neoadjuvant treatment of oral cancer. [2013]Chemoembolization for cancer of the head and neck has been used very rarely in the past owing to local characteristics and risks. By combining the antineoplastic activity and embolizing effect in the same drug, a more routine use seems possible. A cisplatin suspension in normal saline (5 mg in 1 mL) with precipitation of microembolizing cisplatin crystals and without additional drugs was prepared. The cisplatin dosage was 150 mg/m2, the maximum absolute dose 300 mg, and the maximum amount of fluid 60 mL. One hundred and three consecutive patients with previously untreated squamous cell carcinomas of the oral cavity and the anterior oropharynx were treated in a neoadjuvant setting with superselective chemoembolization using the cisplatin suspension. Acceptance by the patients has been excellent with no refusal. Overall response after one intervention has been 73%, with 18.5% showing pathological complete remissions. The highest response rates could be seen in T1-3 tumors and tumors of the oral tongue and floor of the mouth. Measurable acute systemic toxicity has been low. Postembolization syndrome, especially swelling, had to be observed carefully. There have been 3.5% interventional and 10% local complications, which could be significantly reduced by the use of this procedure only in cancers of the oral tongue, floor of the mouth, and mandibular alveolar ridge. Chemoembolization of cancer in the head and neck area can be carried out regularly and safely using this method, and it is highly effective. It could be used as an induction before definitive surgery or radiotherapy. Further investigation is mandatory to assess the potential of chemoembolization for the improvement of local control and survival.
[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]A phase I/II study of postoperative chemoradiotherapy with weekly cisplatin for head and neck squamous cell carcinoma was conducted. The eligiblity of patients were the high risk features, i. e., multiple lymph nodes metastasis(2 or more), extracapusular extension of nodal disease(ECE), or the presence of tumor at the surgical section margins(at 5mm or less). The recommended dose of CDDP in a phase I study was 30mg/m2. We performed a phase II study to assess toxicity and tolerability. We assessed 13 patients, 10 of whom were enrolled in a phase II study, and 3 patients in phase I were given the RD. Acute adverse events were rather mild, including grade 1-2 anemia(50%), mucositis(43%)and nausea/vomiting(43%). One patient required administration of CDDP to be discontinued due to grade 1 renal toxicity. The compliance rate was markedly high(85%: 11/13 patients). We consider weekly CDDP of 30mg/m2 to be a safe regimen in the setting of postoperative adjuvant chemoradiotherapy.
A nanoengineered topical transmucosal cisplatin delivery system induces anti-tumor response in animal models and patients with oral cancer. [2023]Despite therapeutic advancements, oral cavity squamous cell carcinoma (OCSCC) remains a difficult disease to treat. Systemic platinum-based chemotherapy often leads to dose-limiting toxicity (DLT), affecting quality of life. PRV111 is a nanotechnology-based system for local delivery of cisplatin loaded chitosan particles, that penetrate tumor tissue and lymphatic channels while avoiding systemic circulation and toxicity. Here we evaluate PRV111 using animal models of oral cancer, followed by a clinical trial in patients with OCSCC. In vivo, PRV111 results in elevated cisplatin retention in tumors and negligible systemic levels, compared to the intravenous, intraperitoneal or intratumoral delivery. Furthermore, PRV111 produces robust anti-tumor responses in subcutaneous and orthotopic cancer models and results in complete regression of carcinogen-induced premalignant lesions. In a phase 1/2, open-label, single-arm trial (NCT03502148), primary endpoints of efficacy (≥30% tumor volume reduction) and safety (incidence of DLTs) of neoadjuvant PRV111 were reached, with 69% tumor reduction in ~7 days and over 87% response rate. Secondary endpoints (cisplatin biodistribution, loco-regional control, and technical success) were achieved. No DLTs or drug-related serious adverse events were reported. No locoregional recurrences were evident in 6 months. Integration of PRV111 with current standard of care may improve health outcomes and survival of patients with OCSCC.
[Experimental study of cisplatin loaded polylactic acid-polyethylene glycol nano-particles for targeting oral carcinoma]. [2018]To investigate the target deliver of Cisplatin to oral carcinoma tissues by intravenous injection of Cisplatin loaded polylactic acid- polyethylene glycol nanoparticles (CDDP-PLA-PEG-NP).
[The use of two-route Cisplatin chemotherapy in the treatment of oral squamous cell carcinoma]. [2006]To study the feasibility and efficacy of two-route cisplatin chemotherapy for locally advanced squamous cell carcinoma of oral cavity.