Chemotherapy + Reduced-Dose Radiation for Throat Cancer

(ENID Trial)

Overseen By Gregory Biedermann, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Missouri-Columbia

Disqualifiers: Metastatic disease, Prior 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: 1

28 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a new approach to treating HPV-positive throat cancer. It combines standard chemotherapy with Cisplatin and radiation but applies a lower radiation dose to lymph nodes not directly affected by cancer. The aim is to maintain effective cancer control while reducing side effects and improving quality of life after treatment. Individuals with HPV-positive oropharyngeal cancer who do not smoke heavily and have not experienced cancer spread to other body parts might be suitable candidates. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that combining cisplatin with radiation therapy is a common treatment for head and neck cancers. Studies indicate that taking cisplatin weekly or every three weeks results in similar side effects. Most patients experience side effects, such as nausea or low blood counts. Notably, a total dose of 200 mg/m² of cisplatin is linked to better survival rates for these patients.

Regarding radiation therapy, research highlights that newer methods like intensity-modulated radiation therapy (IMRT) cause fewer long-term side effects than older techniques. IMRT effectively controls tumors and reduces side effects, making it a promising choice for many patients. This suggests that the radiation therapy used in this trial might be easier for patients to handle.

Overall, while side effects occur, these treatments are widely used and have well-established safety records. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about combining chemotherapy with reduced-dose radiation for throat cancer because it aims to minimize side effects while maintaining effectiveness. Unlike standard treatments that typically involve full-dose radiation, this approach reduces radiation exposure to unaffected lymph nodes, potentially lessening damage to healthy tissues. By using cisplatin alongside the adjusted radiation levels, the treatment seeks to maintain cancer-fighting power with fewer long-term complications, which is a significant advancement in patient care.

What evidence suggests that this trial's treatments could be effective for throat cancer?

Research has shown that lower doses of radiation combined with the drug cisplatin can effectively treat HPV-positive oropharyngeal cancer. In this trial, all participants will receive this combination treatment. Studies have found that this approach results in a high survival rate, with 96.7% to 97.3% of patients alive after two years. Specifically, after three years, 93% of patients remained alive. This treatment may also enhance quality of life by reducing side effects. Evidence suggests that this combination can effectively manage cancer while minimizing long-term issues. ^{6 7 8 9 10}

Who Is on the Research Team?

Gregory Biedermann, MD

Principal Investigator

University of Missouri - Ellis Fischel Cancer Center

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• Radiation Therapy

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.

How Is the Trial Designed?

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 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 Missouri-Columbia

Lead Sponsor

Trials

387

Recruited

629,000+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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 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]

Citations

1. nrgoncology.org nrgoncology.org/Home/News/Post/reduced-dose-radiation-with-cisplatin-improves-outcomes-for-hpv-associated-oropharyngeal-carcinoma-patients-on-nrg-oncology-study-justifies-phase-iii-trial

Reduced-Dose Radiation with Cisplatin Improves Outcomes f 2-year overall survival rates were 96.7% and 97.3% for the IMRT+C and the IMRT alone arms, respectively. While more grade 3-4 acute toxicities ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8078254/

Reduced-Dose Radiation Therapy for HPV-Associated ... These patients achieved a 3-year overall survival (OS) of 93% compared with 46.2% for those with HPV-negative OPSCC and smoking history > 10 ...

3. mayoclinic.org mayoclinic.org/medical-professionals/cancer/news/de-escalated-therapy-improves-quality-of-life-following-oropharynx-cancer-treatment/mac-20538563

De-escalated therapy improves quality of life following ... In its initial phase 2 trial, DART was associated with a 33% reduction in cost for radiation therapy as well as a 21% reduction in overall ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0385814625000732

Efficacy and safety of definitive low-dose weekly cisplatin ... The 2- and 5-year overall survival (OS) rates were 81.0% and 63.5%, respectively, with a complete response rate of 89.7%. A cumulative cisplatin dose of ≥200 mg ...

5. astro.org astro.org/news-and-publications/news-and-media-center/news-releases/2024/astro24yom

Existing standard chemoradiation superior to ... Randomized trial halted after two deintensification strategies failed to match standard of care's 98% rate of two-year progression-free survival.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11513364/

Retrospective study of cisplatin plus radiotherapy toxicities ... A total of 274 (84%) patients were compliant and received the planned dose of cisplatin. Overall, 957 adverse events were reported in 98.2% of ...

7. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2827612

Weekly Cisplatin Cycles and Outcomes for Chemoradiation ... These findings suggest that missing several cycles of weekly cisplatin is associated with worse survival, even among those with p16-negative tumors.

8. sciencedirect.com sciencedirect.com/science/article/pii/S2772906025000263

Review Article Comparing efficacy and safety of weekly vs. ... Both weekly and triweekly cisplatin regimens show comparable survival outcomes and safety profiles in patients with head and neck cancers, except for short term ...

9. thegreenjournal.com thegreenjournal.com/article/S0167-8140(24)04359-7/fulltext

Predicting cisplatin tolerability in older adults with head ... Cumulative cisplatin doses of ≥ 200 mg/m2 improve survival in adults with head-and-neck squamous cell carcinoma (HNSCC) undergoing ...

10. ascopubs.org ascopubs.org/doi/10.1200/JCO.21.01293

Weekly Cisplatin Plus Radiation for Postoperative Head ... Chemoradiotherapy with weekly cisplatin is noninferior to 3-weekly cisplatin for patients with postoperative high-risk LA-SCCHN.