Nivolumab + Chemotherapy for Nasopharyngeal Cancer

Recruiting at 76 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Immunodeficiency, Autoimmune disease, 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: 16

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment approach for nasopharyngeal carcinoma (NPC), a cancer in the upper part of the throat behind the nose. It combines the immunotherapy drug nivolumab with the chemotherapy drugs cisplatin and gemcitabine before patients undergo radiation therapy. The goal is to determine if this combination can more effectively target and attack cancer cells, potentially reducing the need for intense radiation and its side effects. The trial seeks participants who are 21 years old or younger and have been newly diagnosed with stage II-IV NPC. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic corticosteroids or immunosuppressive medications, you may need to stop them before enrolling. It's best to discuss your specific medications with the trial team.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are on systemic corticosteroids or immunosuppressive medications, you may need to stop them before enrolling. It's best to discuss your specific medications with the trial team.

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

Research has shown that nivolumab, combined with the chemotherapy drugs gemcitabine and cisplatin, has been tested for safety in people with nasopharyngeal cancer. In a study involving 152 patients who received this combination, many experienced side effects. Specifically, 88.2% of patients had some side effects, and 84.9% had more serious ones. These numbers indicate that while the treatment is generally safe, it can cause side effects, some of which might be severe.

Nivolumab is a type of immunotherapy that helps the body's immune system fight cancer. It has been used in other treatments before, and chemotherapy drugs like gemcitabine and cisplatin are commonly used in cancer care. This combination is being tested to determine if it works better or has fewer side effects than previous treatments.

Prospective trial participants should consider these findings and discuss them with their healthcare provider to understand the implications. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using Nivolumab in combination with chemotherapy for nasopharyngeal cancer because it offers a unique approach to treatment. Unlike traditional treatments that mainly involve chemotherapy and radiation, Nivolumab is an immunotherapy drug that works by boosting the body's immune system to target and destroy cancer cells. This mechanism of action is different from conventional methods and may enhance the effectiveness of chemotherapy. Additionally, combining Nivolumab with chemotherapy drugs like cisplatin and gemcitabine could potentially improve outcomes by attacking the cancer on multiple fronts.

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

In this trial, participants will receive a combination of nivolumab, gemcitabine, cisplatin, and radiation therapy. Studies have shown that nivolumab, when combined with chemotherapy and radiotherapy, effectively treats nasopharyngeal carcinoma (NPC) and is generally safe with few side effects. The combination of gemcitabine and cisplatin has also proven to improve survival rates in NPC patients. Research indicates that these drugs help prevent cancer cells from growing and spreading. Together, this treatment combination shows promise in effectively fighting NPC. ^{6 7 8 9 10}

Who Is on the Research Team?

Robyn D Gartrell

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

This trial is for individuals up to 21 years old with newly diagnosed stage II-IV nasopharyngeal carcinoma. Participants need a certain level of physical health (Lansky or Karnofsky score ≥60%), adequate platelet count, and normal kidney function. It's recommended but not required to provide tumor tissue for research.

Inclusion Criteria

I am 21 years old or younger.

My kidney function, measured by creatinine clearance or GFR, is normal or near normal.

My bilirubin levels are within the normal range for my age.

Exclusion Criteria

All patients and/or their parents or legal guardians must sign a written informed consent

I have had radiation therapy to my head or neck.

I am a man who can father a child and agree to use contraception.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Induction Therapy

Patients receive nivolumab, gemcitabine, and cisplatin intravenously over specified durations. Treatment repeats every 21 days for 3 cycles.

9 weeks

3 visits (in-person)

Consolidation Therapy

Patients receive nivolumab and cisplatin intravenously, with concurrent radiation therapy. Treatment repeats every 21 days for 3 cycles.

9 weeks

3 visits (in-person)

Maintenance Therapy

Patients receive nivolumab intravenously. Treatment repeats every 28 days for 6 cycles.

24 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

5 years

Every 3 months for 12 months, every 6 months until 24 months, then yearly

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• Gemcitabine
• Nivolumab
• Radiation Therapy

Trial Overview The study tests the effectiveness of Nivolumab combined with chemotherapy drugs Gemcitabine and Cisplatin, plus radiation therapy in treating nasopharyngeal cancer. The goal is to see if this combination helps the immune system fight cancer better.

How Is the Trial Designed?

Group I: Treatment (nivolumab, gemcitabine, cisplatin, radiation) Experimental Treatment 17 Interventions

See Detailed Description

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 125 patients with locoregionally advanced nasopharyngeal carcinoma, the combination of docetaxel and cisplatin during concurrent chemoradiotherapy resulted in significantly higher rates of severe acute toxicity (88%) compared to docetaxel alone (72%) and cisplatin alone (56%).

Despite the increased toxicity, the combination treatment did not lead to improved survival outcomes, as all treatment groups showed similar 3-year overall survival rates, indicating that more intense chemotherapy may not provide additional benefits in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Acute Toxicities and Efficacy of Concurrent Chemotherapy With Docetaxel Plus Cisplatin, or Docetaxel, or Cisplatin and Helical Tomotherapy in Patients With Locoregionally Advanced Nasopharyngeal Carcinoma: A Randomized Single-Center Phase II Trial. Luo, Y., Cai, B., Li, B., et al.[2022]

In a study involving 33 patients with metastatic nasopharyngeal carcinoma, the efficacy of the nolatrexed and cisplatin (LP) regimen was found to be similar to that of the 5-fluorouracil and cisplatin (FP) regimen, with no significant differences in response rates or survival times.

The LP regimen demonstrated lower toxicity, particularly with a significantly reduced incidence of stomatitis compared to the FP regimen, suggesting it may be a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metastatic nasopharyngeal carcinoma outcomes in patients on cisplatin with nolatrexed or 5-fluorouracil. Zheng, J., Lin, J., Wang, L., et al.[2019]

In a study of 32 patients with metastatic nasopharyngeal carcinoma (NPC), a triplet chemotherapy regimen of paclitaxel, carboplatin, and gemcitabine resulted in a high overall response rate of 78%, with 2 complete responses and 23 partial responses.

While the treatment showed promising efficacy, it also led to significant toxicities, with 41% of patients experiencing severe anemia and thrombocytopenia, and 78% experiencing severe neutropenia, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel, carboplatin, and gemcitabine in metastatic nasopharyngeal carcinoma: a Phase II trial using a triplet combination. Leong, SS., Wee, J., Tay, MH., et al.[2022]

In a study of 822 patients with metastatic nasopharyngeal carcinoma (NPC), the gemcitabine + cisplatin (GP) and paclitaxel + cisplatin + 5-fluorouracil (TPF) regimens showed higher response rates compared to the cisplatin + 5-fluorouracil (PF) regimen.

Despite differences in response rates and toxicity among the five chemotherapy regimens, there were no significant differences in progression-free survival or overall survival, indicating that all regimens (PF, TP, GP) are effective first-line treatments for metastatic NPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of five cisplatin-based regimens frequently used as the first-line protocols in metastatic nasopharyngeal carcinoma. Jin, Y., Shi, YX., Cai, XY., et al.[2022]

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]

In a study of 322 nasopharyngeal carcinoma patients undergoing concurrent chemoradiotherapy, the weekly cisplatin regimen resulted in significantly better 5-year overall survival (96.7% vs. 88.3%) and disease-free survival (90.7% vs. 80.5%) compared to the triweekly regimen.

Both regimens had similar rates of acute toxicities, suggesting that the weekly regimen is not only more effective but also maintains a comparable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of weekly and triweekly cisplatin regimens during concurrent chemoradiotherapy for nasopharyngeal carcinoma. Wang, K., Dong, J., He, S., et al.[2020]

In a phase II study involving 36 patients with recurrent or metastatic nasopharyngeal carcinoma (NPC), the combination of nivolumab and gemcitabine demonstrated a promising objective response rate of 36.1% and a high disease control rate of 97.2%.

The treatment showed a median progression-free survival of 13.8 months with manageable safety, as only 2.8% of patients experienced grade ≥3 treatment-related adverse events like hypertension and anemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II Study of Nivolumab plus Gemcitabine in Patients with Recurrent or Metastatic Nasopharyngeal Carcinoma (KCSG HN17-11). Jung, HA., Park, KU., Cho, S., et al.[2022]

In a phase 3 trial involving 240 patients with N2-3 nasopharyngeal carcinoma, the combination of cisplatin and gemcitabine resulted in a significantly higher 3-year progression-free survival rate of 83.9% compared to 71.5% for the cisplatin-fluorouracil group, indicating better efficacy of the gemcitabine regimen.

While both treatment regimens had adverse effects, the cisplatin-gemcitabine group experienced higher rates of leukopenia and neutropenia, but only one treatment-related death occurred in this group, suggesting that the safety profile is manageable despite the increased toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent chemoradiotherapy followed by adjuvant cisplatin-gemcitabine versus cisplatin-fluorouracil chemotherapy for N2-3 nasopharyngeal carcinoma: a multicentre, open-label, randomised, controlled, phase 3 trial. Liu, LT., Liu, H., Huang, Y., et al.[2023]

In a Phase II trial involving 52 patients with recurrent or metastatic nasopharyngeal carcinoma, the combination of gemcitabine and cisplatin showed a response rate of 51.9%, indicating it is an effective first-line chemotherapy option.

The treatment was generally well-tolerated, with a median overall survival of 14.6 months, although it did have significant side effects, particularly leucopenia in 61.6% of patients, and one treatment-related death due to severe sepsis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine plus cisplatin for patients with recurrent or metastatic nasopharyngeal carcinoma in Taiwan: a multicenter prospective Phase II trial. Hsieh, JC., Hsu, CL., Ng, SH., et al.[2022]

In a study of 37 patients with advanced nasopharyngeal carcinoma, the combination of cisplatin and gemcitabine as induction chemotherapy resulted in an impressive overall response rate of over 90%.

The treatment was well-tolerated, with minimal side effects beyond hematologic toxicities, and led to a 3-year overall survival rate of 76% and a disease-free survival rate of 63% after a median follow-up of 2.9 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction chemotherapy with cisplatin and gemcitabine followed by accelerated radiotherapy and concurrent cisplatin in patients with stage IV(A-B) nasopharyngeal carcinoma. Yau, TK., Lee, AW., Wong, DH., et al.[2022]

In a study of 235 patients with advanced nasopharyngeal carcinoma, the sequential chemotherapy regimen of gemcitabine plus cisplatin (GP) showed significantly better local control rates (96.3%) compared to cisplatin plus fluorouracil (PF) (84.1%), although overall survival rates were similar between the two groups (84.2% for GP vs. 74.4% for PF).

The GP regimen was particularly beneficial for patients classified as T1-3 and those with stage III disease, while both treatment groups experienced low incidences of severe late toxicities, primarily xerostomia and hearing impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing Long-Term Survival and Late Toxicities of Different Sequential Chemotherapy Regimens with Intensity-Modulated Radiotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma. Wu, M., Ou, D., Hu, C., et al.[2021]

In a phase 3 trial involving 362 patients with recurrent or metastatic nasopharyngeal carcinoma, gemcitabine plus cisplatin significantly improved median progression-free survival to 7.0 months compared to 5.6 months for fluorouracil plus cisplatin, establishing it as a more effective first-line treatment option.

While gemcitabine plus cisplatin had a higher incidence of certain severe side effects like leucopenia and neutropenia, it did not result in treatment-related deaths, indicating a manageable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine plus cisplatin versus fluorouracil plus cisplatin in recurrent or metastatic nasopharyngeal carcinoma: a multicentre, randomised, open-label, phase 3 trial. Zhang, L., Huang, Y., Hong, S., et al.[2022]

In a study of 100 patients with recurrent/metastatic nasopharyngeal carcinoma, the combination of gemcitabine (GEM) and cisplatin (DDP) showed significantly better therapeutic efficacy compared to the DDP and fluorouracil (FU) combination.

Patients receiving GEM and DDP experienced fewer side effects, a higher 1-year survival rate, and improved quality of life after 6 months, indicating that this treatment is both effective and well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine Combined with Cisplatin Has a Better Effect in the Treatment of Recurrent/Metastatic Advanced Nasopharyngeal Carcinoma. Yang, Q., Nie, YH., Cai, MB., et al.[2022]

Citations

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Cisplatin-Sparing Regimen Appears Effective for ... The 3-year locoregional recurrence-free survival rate was 92.9% with the cisplatin-sparing regimen and 93.6% with standard therapy (HR, 1.14; 95 ...

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Easing cisplatin's toll in nasopharyngeal carcinoma In this issue of Cancer Cell, Xu et al. achieved favorable outcomes by incorporating nivolumab into standard therapy for locally advanced NPC while removing ...

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Comparing the efficacy and safety of cisplatin ... - BMC Cancer The results showed that some cisplatin-based neoadjuvant chemotherapy regimens improved the prognosis of patients with NPC and reduced the ...

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NCT06064097 | A Study Using Nivolumab, in Combination ... This phase II trial tests effects of nivolumab in combination with chemotherapy drugs prior to radiation therapy patients with nasopharyngeal carcinoma ...

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Nivolumab combined with induction chemotherapy and ... Of the 152 enrolled patients starting gemcitabine-cisplatin (GP) induction chemotherapy plus nivolumab, 134 (88.2%) and 129 (84.9%) experienced ...

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Exploring the Addition of Nivolumab to Platin... (NRG-HN007) “72,987 nasopharyngeal cancer-related deaths were reported worldwide in 2018 according to GLOBOCAN. Currently, patients are treated with ...

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Phase 2 Study Using Chemoimmunotherapy with ... To evaluate safety of combining chemotherapy (cisplatin and gemcitabine) with an anti-PD1 immune checkpoint inhibitor (nivolumab) in children, adolescents and ...