Reduced Radio-Chemotherapy for Oral Cancer

Recruiting at 2 trial locations

Overseen By Teresa Ware, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Florida

Must not be taking: DMRDs, Immunosuppressives

Disqualifiers: Prior cancer treatment, HIV, 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: Unknown

250 Participants Needed

Trial Summary

What is the purpose of this trial?

This study builds on the results of several prior studies that we have been involved with to test the hypothesis that Risk-Adapted De-Intensification of Radiation Therapy and chemotherapy based on HPV subtype, plasma circulating free HPV DNA (cfHPV DNA) level, and cfHPV DNA clearance rate produces Local-Regional Control rates that are similar to what has been achieved with more aggressive therapy in patients with Favorable Prognosis Oropharyngeal Squamous Cell Carcinoma (OPSCC).

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but it does exclude those currently taking Disease Modifying Rheumatoid Drugs (DMRDs) or immunosuppressive medication. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment for oral cancer?

Research shows that combining cisplatin with radiation therapy can improve tumor control and survival in advanced head and neck cancers, although the benefits for oral cancer specifically are not statistically significant. The RADPLAT protocol, which uses high doses of cisplatin with radiation, has shown promising results in controlling tumors and preserving organ function. ^{1 2 3 4 5}

Is reduced radio-chemotherapy with cisplatin and radiation therapy generally safe for humans?

The combination of cisplatin and radiation therapy has shown some safety concerns, including severe nausea, vomiting, and other side effects, but in some studies, the treatment was well-tolerated with low toxicity. More research is needed to fully understand its safety profile. ^{3 6 7 8 9}

How is the RADPLAT treatment for oral cancer different from other treatments?

The RADPLAT treatment is unique because it combines high-dose cisplatin delivered directly into the arteries with radiation therapy, aiming to control the tumor locally while minimizing side effects. This approach may help preserve organ function and improve quality of life compared to traditional treatments that often involve surgery or systemic chemotherapy. ^{1 2 10 11 12}

Research Team

Kathryn Hitchcock, MD, PhD

Principal Investigator

University of Florida

Eligibility Criteria

This trial is for adults with HPV-positive oropharyngeal squamous cell carcinoma who have not smoked heavily in the past 10 years and are eligible for platinum chemotherapy. They must have good organ function, no severe illnesses that could interfere with treatment, and agree to use contraception if they can bear children.

Inclusion Criteria

My recent blood test shows my bone marrow is working well.

My throat cancer is in an early to mid-stage and not spread far.

My kidney and liver tests are normal.

Exclusion Criteria

I am currently on medication for rheumatoid arthritis or to suppress my immune system.

I had surgery to remove my oropharyngeal cancer.

I have had radiotherapy or chemotherapy for my cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemo-radiotherapy

Participants will receive chemo-radiotherapy based on HPV subtype and cfHPV DNA levels

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

• Cisplatin
• Radiation therapy

Trial Overview The study tests whether less intense radiation therapy combined with chemotherapy based on individual risk factors like HPV subtype and cfHPV DNA levels can control cancer as effectively as more aggressive treatments in patients with a favorable prognosis of this type of oral cancer.

Participant Groups

Group I: Chemo-radiotherapy Experimental Treatment 2 Interventions

Participants will receive chemo-radiotherapy.

Cisplatin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

Naveris, Inc.

Industry Sponsor

Trials

1

Recruited

250+

Naveris, Inc.

Collaborator

Trials

1

Recruited

250+

Findings from Research

In a study of 41 patients with advanced oral squamous cell carcinoma, a preoperative treatment combining cisplatin or carboplatin with irradiation resulted in a high overall response rate of 97.6%, with 61% achieving a complete response.

The treatment was well tolerated, with low and reversible side effects, and led to a promising 5-year survival rate of 81.5%, indicating its effectiveness even in advanced stages of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative simultaneous cisplatin- or carboplatin-based chemotherapy and radiotherapy for squamous cell carcinoma of the oral cavity. Kirita, T., Ohgi, K., Tsuyuki, M., et al.[2013]

The RADPLAT approach, which combines supradose intra-arterial cisplatin chemotherapy with radiotherapy, shows promising survival rates and high locoregional tumor control in patients with advanced head and neck squamous cell carcinoma.

This method not only demonstrates acceptable toxicity but also helps preserve organ function, addressing significant concerns associated with traditional surgical treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of advanced head and neck cancer with intra-arterial cisplatin and concurrent radiation therapy: the 'RADPLAT' protocol. Kumar, P., Robbins, KT.[2019]

A phase II trial of cisdiammino-dichloro platinum (CDDP) showed significant effectiveness against testis embryonic carcinoma, ovarian carcinoma, and epidermoid cancers, particularly in head and neck and cervical cancers.

While CDDP demonstrates strong anti-cancer activity, it is associated with notable toxicity primarily affecting the digestive and renal systems, leading to its use in combination therapies for the indicated tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cis-diammino-dichloro-platinum therapy of cancers; phase II therapeutic trial]. Hayat, M., Bayssas, M., Brulé, G., et al.[2013]

In a study involving 20 patients with advanced oral tumors, the combination of low-dose cisplatin with preoperative radiotherapy did not significantly improve local control rates or overall survival compared to radiotherapy alone.

Both treatment groups showed similar outcomes in terms of metastasis incidence and survival rates, indicating that adding low-dose cisplatin may not provide additional benefits for patients undergoing radiotherapy for advanced oral cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Non-randomized study on the effects of preoperative radiotherapy and daily administration of low-dose cisplatin against those of radiotherapy alone for oral cancer--effects on local control, control of metastases, and overall survival]. Kurita, H., Ohtsuka, A., Kobayashi, H., et al.[2013]

The addition of low-dose cisplatin (CDDP) to hyperfractionated radiation therapy (Hfx RT) significantly improved survival rates in patients with locally advanced squamous cell carcinoma of the head and neck, with 68% survival at 2 years compared to 49% with Hfx RT alone.

Despite the survival benefits, the combination treatment did not increase the incidence of severe radiation-induced toxicity compared to Hfx RT alone, although higher rates of hematologic toxicity were observed in patients receiving CDDP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperfractionated radiation therapy with or without concurrent low-dose daily cisplatin in locally advanced squamous cell carcinoma of the head and neck: a prospective randomized trial. Jeremic, B., Shibamoto, Y., Milicic, B., et al.[2022]

In a pilot study involving three patients with advanced head and neck cancer, the combination of radiation therapy and cisplatin (CDDP) resulted in severe side effects, including abscesses and significant nausea and vomiting.

The observed toxicities were greater than expected from either treatment alone, raising concerns about the safety of using this combination in routine clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concomitant radiation therapy and cis-diamminedichloroplatinum (II) in patients with advanced head and neck cancer. Creagan, ET., Fountain, KS., Frytak, S., et al.[2019]

In a pilot study of 28 patients with advanced solid tumors, combining radiotherapy with weekly doses of Cis-dichloro diammine platinum (CDDP) resulted in a complete response in 21 patients, with 11 remaining disease-free at a follow-up of 4-16 months.

The treatment showed low toxicity, with no reported kidney damage or ototoxicity, suggesting that this combination therapy is both effective and safe, although further research with a larger randomized trial is needed for conclusive results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Does CDDP have radiosensitizing properties in the treatment of solid tumors in advanced stage?]. Oliveri, D., Carreca, I., Guarino, A., et al.[2013]

The study found that a combination of cisplatin (CDDP) at 35 mg/m2/week and paclitaxel at 45 mg/m2/week can be safely administered alongside standard radiation therapy (RT) for patients with locally advanced non-small-cell lung cancer (NSCLC), achieving a 60% overall response rate.

Severe esophagitis was the main dose-limiting toxicity, particularly with hyperfractionated RT, leading to treatment adjustments; however, substantial pulmonary or neurologic toxicities were not observed, indicating a relatively safe treatment profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weekly paclitaxel and cisplatin with concurrent radiotherapy in locally advanced non-small-cell lung cancer: a phase I study. Frasci, G., Comella, P., Scoppa, G., et al.[2017]

In a study using human ovarian cancer cell lines, carboplatin (CBDCA) significantly enhanced the lethality of radiation treatment, showing a supra-additive effect, especially when administered before or shortly after radiation exposure.

In contrast, cisplatin (CDDP) did not show the same level of interaction with radiation, indicating that carboplatin may be a more effective option than cisplatin for certain combinations with radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Interactions of carboplatin, cisplatin, and ionizing radiation on a human cell line of ovarian cancer]. Scalliet, P., De Pooter, C., Hellemans, PW., et al.[2019]

The RADPLAT technique, which combines intra-arterial delivery of cisplatin with systemic neutralization using intravenous sodium thiosulphate and concurrent radiotherapy, shows promise in achieving excellent locoregional control rates in patients with unresectable head and neck cancer while minimizing systemic toxicity.

Initial phase II results indicate that RADPLAT may also benefit selected patients with resectable disease by preserving organ function and quality of life, but further phase III randomized controlled trials are needed to compare its efficacy directly with standard intravenous chemoradiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RADPLAT: an alternative to surgery? Alkureishi, LW., de Bree, R., Ross, GL.[2013]

In a phase II study involving 23 patients with head and neck cancer, the combination of paclitaxel and cisplatin resulted in a partial response rate of 32% among evaluable patients, indicating some efficacy.

Despite the observed responses, the significant toxicity, including high rates of asthenia (56%) and other side effects, suggests that this chemotherapy regimen may not be suitable for palliative treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biweekly paclitaxel and cisplatin in patients with advanced head and neck carcinoma. A phase II trial. Licitra, L., Capri, G., Fulfaro, F., et al.[2020]

Satraplatin demonstrated effective antitumor activity against cisplatin-resistant oral squamous cell carcinoma (OSCC) cells, indicating it could be a potential treatment option for patients who do not respond to cisplatin.

The study found that the resistant KB-R cells did not show cross-resistance to satraplatin, and treatment with satraplatin led to cell cycle arrest in the G2/M phase, suggesting a different mechanism of action compared to cisplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of satraplatin in cisplatin-resistant oral squamous cell carcinoma cells. Yamano, Y., Shiiba, M., Negoro, K., et al.[2014]

References

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

Preoperative simultaneous cisplatin- or carboplatin-based chemotherapy and radiotherapy for squamous cell carcinoma of the oral cavity. [2013]

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

Treatment of advanced head and neck cancer with intra-arterial cisplatin and concurrent radiation therapy: the 'RADPLAT' protocol. [2019]

3. France pubmed.ncbi.nlm.nih.gov

[Cis-diammino-dichloro-platinum therapy of cancers; phase II therapeutic trial]. [2013]

4. Japan pubmed.ncbi.nlm.nih.gov

[Non-randomized study on the effects of preoperative radiotherapy and daily administration of low-dose cisplatin against those of radiotherapy alone for oral cancer--effects on local control, control of metastases, and overall survival]. [2013]

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

Hyperfractionated radiation therapy with or without concurrent low-dose daily cisplatin in locally advanced squamous cell carcinoma of the head and neck: a prospective randomized trial. [2022]

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

Concomitant radiation therapy and cis-diamminedichloroplatinum (II) in patients with advanced head and neck cancer. [2019]

7. Italy pubmed.ncbi.nlm.nih.gov

[Does CDDP have radiosensitizing properties in the treatment of solid tumors in advanced stage?]. [2013]

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

Weekly paclitaxel and cisplatin with concurrent radiotherapy in locally advanced non-small-cell lung cancer: a phase I study. [2017]

9. France pubmed.ncbi.nlm.nih.gov

[Interactions of carboplatin, cisplatin, and ionizing radiation on a human cell line of ovarian cancer]. [2019]

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

RADPLAT: an alternative to surgery? [2013]

11. England pubmed.ncbi.nlm.nih.gov

Biweekly paclitaxel and cisplatin in patients with advanced head and neck carcinoma. A phase II trial. [2020]

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

Antitumor activity of satraplatin in cisplatin-resistant oral squamous cell carcinoma cells. [2014]