Chemotherapy and Radiation Based on EBV DNA for Nasopharyngeal Cancer

Recruiting at 221 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: NRG Oncology

Stay on Your Current Meds You can continue your current medications while participating

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

685 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests different combinations of chemotherapy drugs and radiation therapy for advanced nasopharyngeal cancer. It targets patients whose cancer has not spread beyond the local region. The treatment works by killing cancer cells or stopping their growth using powerful drugs and radiation. Previous studies have shown a survival benefit using a combination of these treatments for nasopharyngeal carcinoma.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, a complete list of your current medications will be assessed during the eligibility evaluation.

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

Research shows that using cisplatin and 5-fluorouracil (5-FU) with intensity-modulated radiotherapy (IMRT) is effective for treating nasopharyngeal cancer, especially when combined with monitoring Epstein-Barr virus (EBV) DNA levels. Studies also indicate that adding taxanes like paclitaxel can enhance the effectiveness of cisplatin-based chemoradiation. ^{1 2 3 4 5}

Is the treatment of chemotherapy and radiation based on EBV DNA for nasopharyngeal cancer safe?

The studies show that treatments involving cisplatin, fluorouracil, paclitaxel, and intensity-modulated radiotherapy (IMRT) have been evaluated for safety in nasopharyngeal cancer. These treatments are generally considered tolerable, but they can have side effects, and their safety can vary depending on the specific combination and patient condition. ^{1 2 4 5 6}

How is the chemotherapy and radiation treatment based on EBV DNA for nasopharyngeal cancer different from other treatments?

This treatment is unique because it uses a combination of drugs, including cisplatin, fluorouracil, gemcitabine, and paclitaxel, along with intensity-modulated radiation therapy (IMRT), and monitors the response using Epstein-Barr virus (EBV) DNA levels. This approach is tailored to the presence of EBV, which is linked to nasopharyngeal cancer, and aims to improve treatment effectiveness by adjusting based on EBV DNA levels. ^{1 2 3 4 5}

Research Team

Nancy Lee

Principal Investigator

NRG Oncology

Eligibility Criteria

This trial is for patients with Stage II-IVB nasopharyngeal cancer without distant metastasis. They must have detectable EBV DNA in their plasma, adequate organ function, and agree to use birth control if applicable. Exclusions include major illness affecting trial participation, recent heart issues or infections requiring IV antibiotics, prior malignancies within 3 years (except certain skin cancers), previous chemotherapy or radiotherapy for the study cancer, severe neuropathy, AIDS, and significant co-morbidities.

Inclusion Criteria

Alkaline phosphatase ≤ 1.5 x institutional upper limit of normal

I have been mostly active and able to carry out all pre-disease activities without restriction in the last 3 weeks.

Platelets ≥ 100,000 cells/mm^3

Exclusion Criteria

I have been cancer-free for at least 3 years.

Severe, active co-morbidity

Patients with hearing loss requiring a hearing aid or intervention

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemoradiation

Participants undergo intensity modulated radiation therapy (IMRT) once daily 5 days a week for 6.5 weeks and receive low-dose cisplatin intravenously once weekly during IMRT.

6.5 weeks

EBV DNA Analysis

Plasma samples are collected for EBV DNA analysis 1 week after chemoradiation.

1 week

Adjuvant Treatment

Based on EBV DNA results, patients receive either PF regimen (cisplatin and fluorouracil) or GT regimen (gemcitabine and paclitaxel) or undergo observation.

12-16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment. Follow-up occurs every 4 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Up to 7 years

Treatment Details

Interventions

• Cisplatin
• Fluorouracil
• Gemcitabine Hydrochloride
• Intensity-Modulated Radiation Therapy
• Paclitaxel

Trial Overview The trial tests whether cisplatin and fluorouracil are more effective than gemcitabine hydrochloride and paclitaxel following radiation therapy in treating nasopharyngeal cancer based on EBV DNA levels post-standard treatment. It's a randomized phase II/III study where treatments vary depending on the presence of EBV DNA after initial chemo-radiation therapy.

Participant Groups

Group I: Arm IV (chemoradiation, observation) Experimental Treatment 5 Interventions

Patients undergo clinical observation.

Group II: Arm II (chemoradiation, gemcitabine hydrochloride, paclitaxel) Experimental Treatment 6 Interventions

Patients receive GT regimen comprising paclitaxel IV over 1 hour and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 at least 4 weeks after completion of IMRT. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Group III: Arm I (chemoradiation, cisplatin, fluorouracil) Active Control 5 Interventions

Patients receive PF regimen comprising cisplatin IV over 60-120 minutes and fluorouracil IV over 96 hours continuously beginning at least 4 weeks after completion of IMRT. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.

Group IV: Arm III (chemoradiation, cisplatin, fluorouracil) Active Control 5 Interventions

Patients receive PF regimen as in Arm I of Phase II.

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?

NRG Oncology

Lead Sponsor

Trials

242

Recruited

105,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 155 patients with locoregionally advanced nasopharyngeal carcinoma, treatment with intensity-modulated radiation therapy (IMRT) combined with nedaplatin and either paclitaxel or fluorouracil resulted in high survival rates, with 3-year overall survival rates of 81.6% for the NF group and 83.7% for the NP group.

The study found that the survival outcomes with nedaplatin-based chemotherapy were comparable to those achieved with traditional cisplatin-based regimens, while also reporting acceptable levels of acute and late toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent chemoradiotherapy with nedaplatin plus paclitaxel or fluorouracil for locoregionally advanced nasopharyngeal carcinoma: Survival and toxicity. Xu, J., He, X., Cheng, K., et al.[2015]

References

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

Phase II study of neoadjuvant carboplatin and paclitaxel followed by radiotherapy and concurrent cisplatin in patients with locoregionally advanced nasopharyngeal carcinoma: therapeutic monitoring with plasma Epstein-Barr virus DNA. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Docetaxel, cisplatin and 5-fluorouracil-based induction chemotherapy followed by intensity-modulated radiotherapy concurrent with cisplatin in locally advanced EBV-related nasopharyngeal cancer. [2020]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Pretreatment Epstein-Barr virus DNA load and cumulative cisplatin dose intensity affect long-term outcome of nasopharyngeal carcinoma treated with concurrent chemotherapy: experience of an institute in an endemic area. [2022]

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

Efficacy and safety of concurrent chemoradiotherapy with cisplatin and docetaxel in patients with locally advanced nasopharyngeal cancers. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Concurrent chemotherapy using taxane plus cisplatin versus cisplatin alone in high-risk nasopharyngeal carcinoma patients with suboptimal response to induction chemotherapy. [2023]

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

Concurrent chemoradiotherapy with nedaplatin plus paclitaxel or fluorouracil for locoregionally advanced nasopharyngeal carcinoma: Survival and toxicity. [2015]