Chemotherapy and Radiation Based on EBV DNA for Nasopharyngeal Cancer

Not currently recruiting at 230 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: NRG Oncology

Disqualifiers: Prior invasive malignancy, Hearing loss, AIDS, others

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether different chemotherapy treatments, combined with radiation, can more effectively treat nasopharyngeal cancer, which occurs in the upper part of the throat behind the nose. After initial chemotherapy and radiation, the trial checks for a virus-related DNA marker (EBV DNA) in the blood to decide the next step: additional chemotherapy or observation. Participants must have nasopharyngeal cancer with this viral marker detectable in their blood before starting the trial. The trial aims to determine which post-radiation treatment best combats cancer cells. As a Phase 2, Phase 3 trial, this research measures the treatment's effectiveness in an initial, smaller group and is in the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking cancer treatment advancements.

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.

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

Research shows that the treatments in this trial have been used before, providing valuable safety information.

Studies have shown that the combination of cisplatin and fluorouracil is a common chemotherapy treatment. It is generally well-tolerated, though some patients may experience side effects like nausea or low blood counts, which are often manageable with supportive care.

Past research has also demonstrated the effectiveness of the gemcitabine and paclitaxel combination. Some patients might experience side effects such as tiredness or low blood counts, which are usually manageable with care.

Both treatment options have been used previously, giving doctors insight into their safety. They are not new drugs, so more is known about their effects on the body. However, individual reactions can vary. Always discuss any concerns with your doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for nasopharyngeal cancer because they uniquely tailor chemoradiation based on Epstein-Barr virus (EBV) DNA levels, potentially enhancing precision in treatment. The study includes different arms with distinct combinations of drugs like cisplatin and fluorouracil, or gemcitabine hydrochloride and paclitaxel, each offering alternative approaches to attacking the cancer cells. These combinations aim to optimize effectiveness and minimize side effects compared to traditional chemotherapy regimens alone. By incorporating intensity-modulated radiation therapy (IMRT), the approach also focuses on delivering targeted radiation, reducing damage to surrounding healthy tissue. This personalized strategy could lead to better outcomes and fewer side effects for patients.

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

Research has shown that using gemcitabine and paclitaxel together can help treat certain cancers. In some studies, this combination worked for many patients, with a success rate of 55% to 75%. Patients in these studies lived for an average of 10 to 12 months, which is promising for advanced cases. Both gemcitabine and paclitaxel stop cancer cells from growing and spreading. This trial will evaluate the effectiveness of the gemcitabine and paclitaxel combination for nasopharyngeal cancer in one of the treatment arms. While it's not yet clear if this combination is better than other treatments for nasopharyngeal cancer, early results suggest it could help manage the disease. ^{3 6 7 8 9}

Who Is on the Research Team?

Nancy Lee

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

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

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

Hemoglobin ≥ 8.0 g/dl

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/18615622/

Triplet combination of gemcitabine, paclitaxel, and ...

In the metastatic setting, 2-drug combination chemotherapy generally provides a response rate of 55% to 75%, and median survival of 10 to 12 months. The ...

2.

mycancergenome.org

mycancergenome.org/content/clinical_trials/NCT02135042/

Clinical Trial: NCT02135042

It is not yet known whether giving cisplatin and fluorouracil is more effective than gemcitabine hydrochloride and paclitaxel after radiation ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02135042

Study Details | NCT02135042 | Individualized Treatment in ...

Drugs used in chemotherapy, such as cisplatin, fluorouracil, gemcitabine hydrochloride, and paclitaxel work in different ways to stop the growth of tumor cells, ...

4.

researchgate.net

researchgate.net/publication/8118228_Paclitaxel_carboplatin_and_gemcitabine_in_metastatic_nasopharyngeal_carcinoma_A_Phase_II_trial_using_a_triplet_combination

A Phase II trial using a triplet combination | Request PDF

The median time to disease progression was 8.1 months, and the median overall survival was 18.6 months. The combination of paclitaxel, ...

5.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/15611975/

Paclitaxel, Carboplatin, and Gemcitabine in Metastatic ...

The combination of paclitaxel, carboplatin, and gemcitabine showed promising efficacy against metastatic NPC but at the expense of considerable toxicity.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9308559/

Comparison Efficacy and Safety of Gemcitabine plus Cisplatin ...

To compare the efficacy and safety of gemcitabine plus cisplatin (GP) and 5-fluorouracil plus cisplatin (PF) for metastatic nasopharyngeal ...

7.

cancer.org

cancer.org/cancer/types/nasopharyngeal-cancer/treating/chemotherapy.html

Chemotherapy for Nasopharyngeal Cancer

Chemotherapy (chemo) is a treatment of cancer-killing drugs used to kill nasopharyngeal cancer cells. Learn more about chemotherapy here.

8.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6237045/

Tumor Volume Reduction After Gemcitabine Plus Cisplatin ...

This retrospective study aimed to compare the efficacy of GP and TP (paclitaxel plus cisplatin) regimens in tumor volume reduction after IC.

9.

annalsofoncology.org

annalsofoncology.org/article/S0923-7534(19)39987-9/fulltext

Multicenter phase II study of gemcitabine and oxaliplatin in ...

This multicenter study evaluated the activity of oxaliplatin and prolonged infusion of gemcitabine ('GEMOX' regimen) in recurrent NPC.