Nivolumab + Chemotherapy for Nasopharyngeal Cancer

Recruiting at 53 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

Trial Summary

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.

What data supports the idea that Nivolumab + Chemotherapy for Nasopharyngeal Cancer is an effective treatment?

The available research shows that combining gemcitabine with cisplatin, which are part of the chemotherapy regimen, is effective for treating nasopharyngeal cancer. Studies have shown that this combination can improve outcomes for patients with recurrent or metastatic nasopharyngeal cancer. For example, one study found that this combination had better effects compared to other treatments. However, the research provided does not specifically mention Nivolumab, so its effectiveness in combination with chemotherapy for nasopharyngeal cancer is not directly supported by the data available. ^{1 2 3 4 5}

What data supports the effectiveness of the drug combination of gemcitabine and cisplatin for nasopharyngeal cancer?

Research shows that the combination of gemcitabine and cisplatin is effective in treating recurrent or metastatic nasopharyngeal carcinoma, with studies indicating improved outcomes compared to other chemotherapy regimens. ^{1 2 3 4 5}

What safety data is available for Nivolumab and chemotherapy in nasopharyngeal cancer treatment?

The safety data for chemotherapy regimens involving cisplatin and gemcitabine in nasopharyngeal cancer treatment includes several studies. A Phase II trial in Taiwan evaluated the toxicity of gemcitabine plus cisplatin, while another study compared weekly and triweekly cisplatin regimens, focusing on acute toxicities. A randomized trial assessed acute toxicities of concurrent chemotherapy with docetaxel plus cisplatin, showing high incidences of grade 3 or 4 toxicities, such as mucositis and leukopenia. Another study compared cisplatin-gemcitabine with cisplatin-fluorouracil, and a separate study evaluated cisplatin and gemcitabine as induction chemotherapy, both focusing on efficacy and toxicity. These studies provide insights into the safety profile of these chemotherapy combinations, although specific data on Nivolumab in combination with these regimens is not detailed in the provided abstracts. ^{2 6 7 8 9}

Is the combination of Nivolumab and chemotherapy safe for treating nasopharyngeal cancer?

Studies have shown that chemotherapy combinations like cisplatin and gemcitabine can cause significant side effects, including severe mucositis (painful inflammation and ulceration of the mucous membranes), leukopenia (low white blood cell count), and neutropenia (low levels of neutrophils, a type of white blood cell). These side effects were common in patients with nasopharyngeal cancer undergoing treatment, indicating that while the treatment can be effective, it also carries risks of serious side effects. ^{2 6 7 8 9}

Is the drug combination of Cisplatin, Gemcitabine, and Nivolumab promising for nasopharyngeal cancer?

Yes, the combination of Cisplatin, Gemcitabine, and Nivolumab is promising for treating nasopharyngeal cancer. Studies show that using Nivolumab with Gemcitabine can be effective for patients who did not respond to previous treatments. This combination could improve treatment results for this type of cancer. ^{4 10 11 12 13}

How is the drug combination of Nivolumab, Cisplatin, and Gemcitabine unique for treating nasopharyngeal cancer?

This treatment is unique because it combines Nivolumab, an immune system booster, with chemotherapy drugs Cisplatin and Gemcitabine, potentially enhancing effectiveness against nasopharyngeal cancer compared to using chemotherapy alone. ^{4 10 11 12 13}

What is the purpose of this trial?

This phase II trial tests effects of nivolumab in combination with chemotherapy drugs prior to radiation therapy patients with nasopharyngeal carcinoma (NPC). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as gemcitabine and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Researchers want to find out what effects, good and/or bad, adding nivolumab to chemotherapy has on patients with newly diagnosed NPC. In addition, they want to find out if children with NPC may be treated with less radiation therapy and whether this decreases the side effects of therapy.

Research Team

Robyn D Gartrell

Principal Investigator

Children's Oncology Group

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: Treatment (nivolumab, gemcitabine, cisplatin, radiattion) 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+

Findings from Research

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 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 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 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 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]

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 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 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 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 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 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 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]

References

1. United States 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. [2021]

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

Gemcitabine plus cisplatin for patients with recurrent or metastatic nasopharyngeal carcinoma in Taiwan: a multicenter prospective Phase II trial. [2022]

3. England 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. [2022]

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

Paclitaxel, carboplatin, and gemcitabine in metastatic nasopharyngeal carcinoma: a Phase II trial using a triplet combination. [2022]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Gemcitabine Combined with Cisplatin Has a Better Effect in the Treatment of Recurrent/Metastatic Advanced Nasopharyngeal Carcinoma. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Comparison of weekly and triweekly cisplatin regimens during concurrent chemoradiotherapy for nasopharyngeal carcinoma. [2020]

7. United States 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. [2022]

8. England 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. [2023]

9. United States 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. [2022]

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

A Phase II Study of Nivolumab plus Gemcitabine in Patients with Recurrent or Metastatic Nasopharyngeal Carcinoma (KCSG HN17-11). [2022]

11. Germany pubmed.ncbi.nlm.nih.gov

Comparison of five cisplatin-based regimens frequently used as the first-line protocols in metastatic nasopharyngeal carcinoma. [2022]

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

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

13. Switzerland pubmed.ncbi.nlm.nih.gov

Metastatic nasopharyngeal carcinoma outcomes in patients on cisplatin with nolatrexed or 5-fluorouracil. [2019]