What is the mechanism of action of this treatment?

Cisplatin forms DNA crosslinks that prevent DNA replication and transcription, leading to cell death, while Fluorouracil inhibits thymidylate synthase, blocking DNA synthesis. Gemcitabine, a nucleoside analog, incorporates into DNA, causing chain termination and inhibiting DNA synthesis. Paclitaxel stabilizes microtubules, preventing their disassembly and disrupting cell division. These mechanisms are crucial for EBV infection patients as they target rapidly dividing cells, including cancerous cells associated with EBV, thereby reducing tumor growth and spread.

What side effects are associated with this type of intervention?

Cisplatin and Fluorouracil are commonly associated with side effects such as nausea, vomiting, nephrotoxicity, myelosuppression, and mucositis. Gemcitabine and Paclitaxel can cause neutropenia, neuropathy, fatigue, and diarrhea. Both regimens can lead to significant toxicity, requiring careful management.

What prior FDA approvals exist?

There are no specific FDA-approved treatments for Epstein-Barr Virus (EBV) infection that directly match the mechanisms of Cisplatin and Fluorouracil (DNA crosslinking and inhibition of DNA synthesis) or Gemcitabine and Paclitaxel (inhibition of DNA synthesis and microtubule stabilization). Current treatments for EBV-related conditions, such as nasopharyngeal carcinoma, may involve these chemotherapeutic agents, but they are not approved specifically for treating EBV infection itself.

What other types of research exist?

Promising novel alternatives for treating EBV infection in patients could include PARP inhibitors like Olaparib, which target DNA repair mechanisms, and immune checkpoint inhibitors such as Pembrolizumab, which enhance the immune system's ability to fight cancer. Additionally, novel antibody-drug conjugates and targeted therapies like RET inhibitors (e.g., Selpercatinib) may offer new avenues for treatment.

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Alkylating agents

Chemotherapy and Radiation Based on EBV DNA for Nasopharyngeal Cancer

Phase 2 & 3

Waitlist Available

Led By Nancy Lee

Research Sponsored by NRG Oncology

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Stage II-IVB disease with no evidence of distant metastasis

Biopsy proven diagnosis of cancer of the nasopharynx

Must not have

Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration

Pregnancy or unwillingness to use contraception

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 7 years

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects include nausea, vomiting from chemotherapy drugs like cisplatin and fluorouracil; fatigue from radiation; possible allergic reactions to medications; blood count changes leading to increased infection risk; liver function alterations; hearing loss primarily if sensorineural in nature.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My cancer is between stage II and IVB and has not spread far.

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My cancer in the upper part of my throat has been confirmed by a biopsy.

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My kidney function is within the normal range.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am currently on IV antibiotics for a bacterial or fungal infection.

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I am not pregnant and willing to use contraception.

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

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I've had radiation in the same area as my current cancer.

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I have moderate to severe numbness, tingling, or pain in my hands or feet.

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I have not had a heart attack in the last 6 months.

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I have received chemotherapy for my current cancer.

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I have been diagnosed with AIDS according to CDC guidelines.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 7 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 7 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 7 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Overall survival (OS) (Undetectable Plasma EBV DNA Cohort Phase III)

Progression-free survival (PFS) (Detectable Plasma EBV DNA Cohort Phase II)

Secondary study objectives

Changes in QOL (hearing) as assessed by the Hearing Handicap Inventory for the Elderly-Screening version (HHIE-S) (Phase II and III)

Changes in pure tone audiometry (Phase II and III)

Changes in quality of life (QOL) (general and physical well-being) assessed using the Functional Assessment of Cancer Therapy (FACT)-Nasopharyngeal (NP) (Phase II and III)

+8 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

4Treatment groups

Experimental Treatment

Active Control

Group I: Arm IV (chemoradiation, observation)Experimental Treatment5 Interventions

Patients undergo clinical observation.

Group II: Arm II (chemoradiation, gemcitabine hydrochloride, paclitaxel)Experimental Treatment6 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 Control5 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 Control5 Interventions

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Cisplatin

2013

Completed Phase 3

~3120

Intensity-Modulated Radiation Therapy

2010

Completed Phase 3

~2140

Gemcitabine Hydrochloride

2005

Completed Phase 3

~5420

Paclitaxel

2011

Completed Phase 4

~5450

0 / 11Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Cisplatin forms DNA crosslinks that prevent DNA replication and transcription, leading to cell death, while Fluorouracil inhibits thymidylate synthase, blocking DNA synthesis. Gemcitabine, a nucleoside analog, incorporates into DNA, causing chain termination and inhibiting DNA synthesis. Paclitaxel stabilizes microtubules, preventing their disassembly and disrupting cell division. These mechanisms are crucial for EBV infection patients as they target rapidly dividing cells, including cancerous cells associated with EBV, thereby reducing tumor growth and spread.

RNA-seq and integrated network analysis reveals the hub genes and key pathway of paclitaxel inhibition on Adriamycin resistant diffuse large B cell lymphoma cells.Sequence specificity, conformation, and recognition by HMG1 protein of major DNA interstrand cross-links of antitumor dinuclear platinum complexes.