Chemotherapy + Reduced-Dose Radiation for Throat Cancer

(ENID Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Gregory Biedermann, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of Missouri-Columbia

Disqualifiers: Metastatic disease, Prior chemotherapy, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial will explore giving standard dose chemotherapy and radiation therapy to sites of disease including all lymph nodes involved with HPV-positive oropharyngeal cancer, but administer lower doses of radiation therapy to the lymph nodes that are not known to be involved with cancer. By doing so, it is hypothesized that there will be equally good long term loco-regional and distant disease control but will reduced long term treatment side effects and improved quality of life in persons living well beyond their cancer treatment.

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 for throat cancer?

Research shows that using cisplatin with radiation therapy, like in the RADPLAT protocol, can effectively control tumors in head and neck cancers, offering promising survival rates and preserving organ function. ^{1 2 3 4 5}

Is the combination of chemotherapy and reduced-dose radiation safe for throat cancer?

The combination of chemotherapy (cisplatin) and radiation therapy has been studied for head and neck cancers, showing some safety concerns. Patients experienced severe nausea, vomiting, and other side effects, but overall, the treatment was considered effective and generally well-tolerated in some studies, with gastrointestinal and blood-related side effects being the most common. ^{6 7 8 9 10}

How is the treatment of chemotherapy combined with reduced-dose radiation for throat cancer different from other treatments?

This treatment is unique because it combines chemotherapy with a reduced dose of radiation, potentially minimizing side effects while maintaining effectiveness. Cisplatin is often used in combination with radiation for head and neck cancers, but this approach specifically aims to reduce radiation exposure, which may lead to fewer long-term complications compared to standard radiation doses. ^{4 5 11 12 13}

Research Team

Gregory Biedermann, MD

Principal Investigator

University of Missouri - Ellis Fischel Cancer Center

Eligibility Criteria

This trial is for low-risk patients with HPV-positive oropharyngeal cancer who have not had prior invasive malignancies (except certain skin cancers) in the last 5 years, no previous radiotherapy overlapping the study area, and no chemotherapy for their current cancer. They must be generally healthy, non-heavy smokers or willing to quit, and women of childbearing age should use contraception.

Inclusion Criteria

I have been diagnosed with a specific type of throat cancer.

I've had a throat exam using a special scope within the last 60 days.

I have had an MRI of the neck with contrast and a chest CT scan.

Exclusion Criteria

My cancer is in the early stages and located in my tonsil.

My cancer originates from the mouth, nasopharynx, hypopharynx, or larynx.

I have been cancer-free for at least 5 years, except for non-melanoma skin cancer.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemoradiation Treatment

Participants receive concurrent cisplatin and radiation therapy with dose de-escalation to uninvolved lymph nodes

6 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including survival and toxicity profiles

2 years

Visits at 1 month, 6 months, 1 year, and 2 years post-treatment

Treatment Details

Interventions

• Cisplatin (Alkylating agents)
• Radiation Therapy (Radiation)

Trial Overview The trial tests if giving standard dose chemotherapy alongside radiation therapy directly to areas affected by HPV-positive oropharyngeal cancer—and lower doses to unaffected lymph nodes—can control the disease while reducing long-term side effects and improving life quality after treatment.

Participant Groups

Group I: Open label single-arm study Experimental Treatment 1 Intervention

All patients will receive concurrent cisplatin and radiation therapy with radiation dose de-escalation to clinically and radiologically uninvolved lymph nodes.

Cisplatin is already approved in Canada, Japan for the following indications:

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 Missouri-Columbia

Lead Sponsor

Trials

387

Recruited

629,000+

Mun Y. Choi

University of Missouri-Columbia

Chief Executive Officer since 2017

PhD in Mechanical and Aerospace Engineering from Princeton University

Richard Barohn

University of Missouri-Columbia

Chief Medical Officer since 2020

MD from the University of Missouri-Columbia School of Medicine

Findings from Research

In a phase II trial involving 32 patients with advanced head and neck cancer, the aggressive combination of cisplatinum and paclitaxel with hyperfractionated-accelerated radiotherapy resulted in a 5-year overall survival rate of 48% and a disease-free survival rate of 43%.

While the treatment showed promising response rates, with 69% achieving a complete response, it was associated with significant acute toxicities, including high rates of grade 3 mucositis (71%) and erythema (28%), indicating the need for extensive supportive care during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of a simultaneous radiochemotherapy with cisplatinum and paclitaxel in combination with hyperfractionated-accelerated radiotherapy in locally advanced head and neck tumors. Kuhnt, T., Becker, A., Bloching, M., et al.[2022]

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]

In a study comparing cisplatin and cetuximab added to radiation therapy for head and neck squamous cell carcinoma, patients receiving cisplatin had a significantly higher 3-year disease-specific survival rate of 83% compared to 31% for those receiving cetuximab.

Cisplatin treatment was associated with a lower recurrence rate of disease (4 patients) compared to cetuximab (17 patients), indicating that cisplatin may be more effective in improving outcomes when combined with radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cisplatin versus cetuximab given concurrently with definitive radiation therapy for locally advanced head and neck squamous cell carcinoma. Ley, J., Mehan, P., Wildes, TM., et al.[2021]

Carboplatin-based chemoradiation therapy (CTRT) is a well-tolerated alternative for patients with locally advanced head and neck cancers who are unfit for cisplatin, with 84.1% of patients completing the planned treatment.

The study found a median overall survival of 28 months and progression-free survival of 17 months, suggesting that carboplatin-based CTRT may offer better outcomes compared to radical radiotherapy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin-based concurrent chemoradiation therapy in locally advanced head and neck cancer patients who are unfit for cisplatin therapy. Noronha, V., Sharma, V., Joshi, A., et al.[2018]

A reduced RADPLAT protocol using intra-arterial cisplatin and irradiation showed promising local control in advanced laryngeal cancer, with 67.5% of patients achieving local control and an overall survival rate of 80% after 3 years.

The treatment was well-tolerated, with only a few cases of severe side effects, and no patients required tube feeding, indicating a favorable safety profile for this chemoradiotherapy regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent intra-arterial chemotherapy and radiotherapy for advanced laryngeal cancer. Yoshizaki, T., Kondo, S., Wakisaka, N., et al.[2018]

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]

Concurrent chemotherapy with radiotherapy has been shown to improve overall survival in various solid tumors, particularly with platinum-containing regimens like cisplatin and carboplatin.

The article focuses on the effectiveness of platinum-based chemotherapy combined with radiotherapy specifically for squamous-cell carcinomas of the head and neck and esophageal carcinomas, highlighting the need for ongoing research to determine the optimal treatment combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Platinum-based concurrent chemoradiotherapy for tumors of the head and neck and the esophagus. Hao, D., Ritter, MA., Oliver, T., et al.[2005]

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 of 35 patients with advanced squamous cell carcinoma of the head and neck, the combination of cis-platinum (CDDP) and radiotherapy (RT) resulted in a high complete response rate of 75%, with an overall response rate of 100%.

The treatment was well tolerated, with gastrointestinal and hematologic toxicities being the most common side effects, making CDDP plus RT a safe and effective option, especially for patients with good performance status and unresectable stage II or III disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simultaneous cis-platinum and radiotherapy in inoperable or locally advanced squamous cell carcinoma of the head and neck. Gasparini, G., Pozza, F., Recher, G., et al.[2018]

Combined treatment of radiotherapy with cisplatin and etoposide has shown significant improvements in local control and survival rates for patients with locally advanced non-small cell lung cancer (NSCLC), with median survival rates reported between 15-18 months and 2-year survival rates around 35-40%.

Recent advancements in radiation technology and the use of third-generation chemotherapy drugs have led to promising results, including median survival exceeding 20 months, although careful management of treatment to minimize toxicity, particularly esophageal toxicity, remains crucial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy and chemotherapy in locally advanced non-small cell lung cancer: preclinical and early clinical data. Reboul, FL.[2019]

In a phase II trial involving 32 patients with recurrent or metastatic head and neck squamous cell carcinoma, the combination of carboplatin and raltitrexed demonstrated moderate efficacy, with a 22% partial response rate and a median survival duration of 9.8 months.

The treatment was generally safe, with manageable toxicity; however, 25% of patients experienced severe neutropenia, and one patient dropped out due to persistent hepatic toxicity, indicating the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin in combination with raltitrexed in recurrent and metastatic head and neck squamous cell carcinoma: A multicentre phase II study of the Gruppo Oncologico Dell'Italia Meridionale (G.O.I.M.). Galetta, D., Giotta, F., Rosati, G., et al.[2014]

Carboplatin and cisplatin both provide a survival benefit when used alongside radiation therapy for patients with locally advanced head and neck squamous cell carcinoma, with cisplatin showing potentially greater activity but carboplatin being better tolerated.

The most commonly used regimen for cisplatin is 100 mg/m² every 3 weeks during radiation therapy, although there is no consensus on the optimal total dose needed for effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In squamous cell head and neck cancer: which platinum, how much and how often? Nwizu, T., Adelstein, DJ.[2019]

Preoperative simultaneous radiation therapy combined with Cisplatin (CTRT) significantly improved treatment outcomes in patients with Stage III/IV head and neck squamous cell carcinoma, showing a 68% complete clinical response compared to 36% in the control group.

CTRT also resulted in lower toxicity rates (45% vs 76% in the control group) and reduced recurrence (33% vs 66%), suggesting it may be a more effective and safer treatment option for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative simultaneous fractionated cisplatin and radiation therapy in the treatment of advanced operable stage III and IV squamous cell carcinoma of the head and neck. Davis, MA., Tyrrell, J., Slotman, GJ., et al.[2019]

References

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

Phase II trial of a simultaneous radiochemotherapy with cisplatinum and paclitaxel in combination with hyperfractionated-accelerated radiotherapy in locally advanced head and neck tumors. [2022]

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. Switzerland pubmed.ncbi.nlm.nih.gov

Cisplatin versus cetuximab given concurrently with definitive radiation therapy for locally advanced head and neck squamous cell carcinoma. [2021]

4. India pubmed.ncbi.nlm.nih.gov

Carboplatin-based concurrent chemoradiation therapy in locally advanced head and neck cancer patients who are unfit for cisplatin therapy. [2018]

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

Concurrent intra-arterial chemotherapy and radiotherapy for advanced laryngeal cancer. [2018]

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

Platinum-based concurrent chemoradiotherapy for tumors of the head and neck and the esophagus. [2005]

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. Switzerland pubmed.ncbi.nlm.nih.gov

Simultaneous cis-platinum and radiotherapy in inoperable or locally advanced squamous cell carcinoma of the head and neck. [2018]

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

Radiotherapy and chemotherapy in locally advanced non-small cell lung cancer: preclinical and early clinical data. [2019]

11. Greece pubmed.ncbi.nlm.nih.gov

Carboplatin in combination with raltitrexed in recurrent and metastatic head and neck squamous cell carcinoma: A multicentre phase II study of the Gruppo Oncologico Dell'Italia Meridionale (G.O.I.M.). [2014]

12. England pubmed.ncbi.nlm.nih.gov

In squamous cell head and neck cancer: which platinum, how much and how often? [2019]

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

Preoperative simultaneous fractionated cisplatin and radiation therapy in the treatment of advanced operable stage III and IV squamous cell carcinoma of the head and neck. [2019]