Reduced Radio-Chemotherapy for Oral Cancer

Recruiting in Palo Alto (17 mi)

+2 other locations

Overseen by Kathryn Hitchcock, MD, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of Florida

Must not be taking: DMRDs, Immunosuppressives

Disqualifiers: Prior cancer treatment, HIV, others

No Placebo Group

Prior Safety Data

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.

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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.

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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.

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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.

Trial 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

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

UF Health Proton Therapy Institute Jacksonville, FL

University of Florida Gainesville, FL

Medical University of South Carolina Charleston, SC

Who Is Running the Clinical Trial?

University of Florida Lead Sponsor

Naveris, Inc. Industry Sponsor

Naveris, Inc. Collaborator

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] Encouraging results have been reported with cisplatin- or carboplatin-based chemotherapy regimens and simultaneous irradiation treatment in advanced and unresectable head and neck head and neck cancer. We have therefore examined the effectiveness of such therapy on tumor control, survival, and toxicity in patients with advanced oral squamous cell carcinoma.

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] The prognosis for patients presenting with advanced head and neck squamous cell carcinoma using "standard" treatment approaches, such as surgery followed by radiotherapy or radiotherapy alone, remains poor. Additionally, patients often lose their voice or swallowing ability when a primary surgical approach is used. Although systemic chemotherapy, when combined concurrently with radiotherapy, appears to be superior to radiation alone, the use of neoadjuvant or adjuvant systemic chemotherapy has not improved survival when combined with either surgery or radiotherapy. Even with the use of concurrent systemic chemotherapy and radiotherapy, the majority of the patients still succumb to their disease, usually failing locoregionally. Among the newer strategies being explored is the use of supradose intra-arterial chemotherapy (ie, cisplatin) with current radiotherapy. Acronymed "RADPLAT," this novel therapeutic approach delivers supradoses of weekly cisplatin chemotherapy with concurrent radiotherapy with acceptable toxicity, high locoregional tumor control rates, and very promising survival results. In addition, the RADPLAT approach allows for the preservation of organ function. This article reviews the evolution of the RADPLAT concept from a phase I trial to a recently completed Radiation Therapy Oncology Group trial confirming its feasibility in a multi-institutional setting.

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

[Cis-diammino-dichloro-platinum therapy of cancers; phase II therapeutic trial]. [2013] We have conducted a phase II trial of cisdiammino-dichloro platinum (CDDP) which demonstrates its remarkable activity in testis embryonic carcinoma, in ovary carcinoma and in epidermoid cancers, especially head and neck and uterus cervix carcinoma. Its toxicity in mainly digestive and renal. This compound is now indicated in combinations in the case of the above mentioned tumors.

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] Cisplatin is a known radiation modifier. Our previous study suggested that daily administration of low-dose cisplatin enhanced the efficacy of radiotherapy against primary oral squamous carcinoma. In this paper, we follow the patients who participated in the previous study and survey the benefit of combination low-dose cisplatin in improving local control, prevention of metastases, and overall survival. This study included patients with surgically resectable advanced oral tumors. Ten patients underwent preoperative radiotherapy of 30-40 Gy/15-20 days with concomitant daily administration of low-dose cisplatin (5 mg/body or 5 mg/m2). Ten other patients received external radiotherapy alone. All patients then underwent a planned radical tumor resection. No significant difference was see in loco-regional control rates (primary: 86 vs. 88%, neck: 83 vs. 78% at 48 months) or incidence of metastasis (70 vs. 64%) between the two groups. Nor was there a significant difference in the overall survival rate (60 vs. 66%). The results of this study suggest that the concomitant use of daily administration of low-dose cisplatin with preoperative radiation brings no statistically significant benefit in improving local control and survival rate in patients with advanced resectable oral cancer.

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] To investigate whether the addition of cisplatin (CDDP) to hyperfractionation (Hfx) radiation therapy (RT) offers an advantage over the same Hfx RT given alone in locally advanced (stages III and IV) squamous cell carcinoma of the head and neck.

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

Concomitant radiation therapy and cis-diamminedichloroplatinum (II) in patients with advanced head and neck cancer. [2019] Three patients with locally advanced head and neck squamous cell cancer received concomitant radiation therapy (XRT) and cis-diamminedichloroplatinum (CDDP). The dose of 6,000 rads was to be administered in two 3,000-rad courses separated by 3 weeks. The CDDP, 30 mg/m2, was to be given intravenously on days 2 and 12 of each half of XRT. We were especially concerned with the occurrence of an abscess in one patient and an abscess with hemorrhage in another. In addition, each patient experienced severe and intractable nausea, vomiting, and a pervasive feeling of ill-health which seemed out of proportion to that usually observed from either XRT or CDDP alone. If the findings in this pilot study are confirmed, the toxicity of XRT with concurrent CDDP as used in our study may well obviate routine clinical usage.

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

[Does CDDP have radiosensitizing properties in the treatment of solid tumors in advanced stage?]. [2013] Various experimental and clinical studies have signalled the radiosensitizing properties of CDDP (Cis-dichloro diammine platinum). Twenty eight patients with advanced solid tumours were included in a pilot study incorporating classic fraction (2.00 Gy X 5 weeks) radiotherapy and weekly doses of 30 g/sq.m CDDP. A complete response was obtained in 21 patients with 11 of them NED at a mean follow-up period of 4-16 months. The toxicity of the treatment was low and no kidney damage or ototoxicity was encountered. The results obtained by the combined treatment are encouraging but a correct assessment will require a randomised trial on a bigger patient sample.

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] Both cisplatin (CDDP) and paclitaxel have shown good antitumor activity in non-small-cell lung cancer (NSCLC) patients and are able to potentiate the antitumor effects of radiation therapy (RT). This study aimed to determine the maximum-tolerated doses (MTDs) of CDDP and paclitaxel (escalated alternately) when given concurrently with RT and to define the nature of the dose-limiting toxicity (DLT).

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

[Interactions of carboplatin, cisplatin, and ionizing radiation on a human cell line of ovarian cancer]. [2019] Cisplatin (CDDP) and radiotherapy are frequently used concomitantly in the treatment of various malignant conditions. Because of its toxicity, cisplatin tends to be replaced by carboplatin (CBDCA) in several indications. Available data regarding the combined effects of cisplatin and carboplatin with ionising radiation are contradictory.

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

RADPLAT: an alternative to surgery? [2013] Head and neck cancer frequently presents at a late stage, leading to a poor prognosis despite optimal treatment with surgery and/or radiotherapy. Chemotherapy for advanced disease has shown little benefit as a single-modality treatment, and the use of concurrent chemoradiation is limited by problems with severe toxicity at higher doses. RADPLAT is the acronym used to describe a new technique, combining intra-arterial delivery of cisplatin with systemic neutralization by i.v. sodium thiosulphate, and concurrent radiotherapy. This allows very high cisplatin dose intensities to be used while potentially minimizing adverse systemic effects. Initial results suggest that excellent locoregional control rates are achievable in patients with unresectable disease, with a favorable side-effect profile when compared with conventional chemoradiation protocols. In addition, RADPLAT may potentially be of benefit in selected patients with resectable disease, allowing for preservation of organ function and quality of life without compromising locoregional control or survival. While current phase II data are encouraging, phase III randomized controlled trials are required in order to directly compare RADPLAT with i.v. chemoradiation therapy, the current standard of care. This article reviews the evolution of the RADPLAT concept, from initial clinical trials to its current application in the treatment of patients with advanced head and neck cancer.

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

Biweekly paclitaxel and cisplatin in patients with advanced head and neck carcinoma. A phase II trial. [2020] Cisplatin is an active drug in head and neck cancer. Paclitaxel seems a promising drug. This article reports a phase II assessment of the combination of the two.

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

Antitumor activity of satraplatin in cisplatin-resistant oral squamous cell carcinoma cells. [2014] The aim of the current study was to identify the antitumor activity of satraplatin in paired cisplatin (CDDP)-resistant oral squamous cell carcinoma (OSCC) cell line and its parental cell line.