Gemcitabine + Docetaxel + Toripalimab for Nasopharyngeal Cancer

Overseen By Elizabeth Winters

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Stanford University

Must not be taking: Anticancer treatments

Disqualifiers: Autoimmune disease, Organ transplant, AIDS, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of drugs, including toripalimab (an immunotherapy drug), to determine their safety and effectiveness in treating nasopharyngeal cancer, which occurs in the upper part of the throat behind the nose. The treatment combines chemotherapy drugs and radiation. It targets individuals with advanced nasopharyngeal cancer who have not received prior treatment for this condition. Participants should have Epstein-Barr virus-positive nasopharyngeal cancer and be able to perform daily activities with some or no difficulty. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use any other anti-cancer treatments while participating.

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

A study with patients who have nasopharyngeal cancer found that adding Toripalimab to chemotherapy was generally safe. While some immune-related side effects occurred, they were usually manageable. Another study showed that combining Toripalimab with gemcitabine and docetaxel resulted in no treatment-related deaths. The most common side effects were headaches and nausea. Overall, current research indicates that the treatment is well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for nasopharyngeal cancer, which typically involve chemotherapy and radiation, toripalimab adds a new dimension by utilizing the body's own immune system to fight the cancer. Toripalimab is a type of immunotherapy called a PD-1 inhibitor, which works by blocking the pathway that cancer cells use to hide from immune cells. This means it can potentially help the immune system recognize and attack cancer cells more effectively. Researchers are excited about toripalimab because it offers a promising new approach to treatment, especially for patients who may not respond well to conventional therapies.

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

Research has shown that a combination of three drugs—gemcitabine, docetaxel, and toripalimab—may effectively treat nasopharyngeal cancer. In one study involving 22 patients with this cancer type, 72% experienced tumor shrinkage or disappearance. Additionally, 63% of the patients saw a significant decrease in tumor size. Toripalimab, which participants in this trial will receive, is a PD-1 inhibitor believed to enhance the body's immune response against cancer. This promising data suggests that this treatment combination could be effective. ^{1 2 4 6 7}

Who Is on the Research Team?

A Dimitrios Colevas, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

This trial is for individuals with nasopharyngeal carcinoma associated with the Epstein-Barr Virus. Specific eligibility criteria are not provided, but typically participants would need to meet certain health standards and have a confirmed diagnosis of the condition being studied.

Inclusion Criteria

Life expectancy: 3 months at least

CBC/differential obtained within 21 days prior to day 1 of treatment, with adequate bone marrow function defined as follows:

Platelets ≥ 100,000 cells/mm3

Exclusion Criteria

I am not currently using any cancer treatments.

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

I have received systemic anticancer treatment for nasopharyngeal cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Chemotherapy

Participants receive three q 21-day cycles of gemcitabine, docetaxel, and toripalimab

12 weeks

Radiation

Participants receive radiation to 70 Gy plus concurrent weekly cisplatin

8 weeks

Adjuvant Therapy

Participants receive adjuvant capecitabine and toripalimab

1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Toripalimab

Trial Overview The study tests Toripalimab's safety and effectiveness in treating EBV-associated nasopharyngeal cancer, alongside standard treatments like concurrent chemoradiation followed by adjuvant therapy.

How Is the Trial Designed?

Group I: Gemcitabine, Docetaxel and Capecitabine Experimental Treatment 2 Interventions

Patients will receive three q 21-day cycles of gemcitabine 1000 mg/m2 plus docetaxel 75 mg/m2 plus toripalimab 240 mg, followed by radiation to 70 Gy plus concurrent weekly cisplatin, 40 mg/m2 up to 7 doses, followed by adjuvant capecitabine 650 mg/m2 BID for one year plus toripalimab 240 mg q 21 days for 9 doses.

Toripalimab is already approved in China, United States for the following indications:

Approved in China as Loqtorzi for:

• Nasopharyngeal carcinoma
• Esophageal cancer
• Small cell lung cancer

Approved in United States as toripalimab for:

• Under review for nasopharyngeal carcinoma and small cell lung cancer

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Published Research Related to This Trial

In a phase 3 trial involving 289 patients with recurrent or metastatic nasopharyngeal carcinoma, the addition of toripalimab to standard gemcitabine-cisplatin chemotherapy significantly improved progression-free survival (PFS) from 8.0 months to 11.7 months, indicating enhanced treatment efficacy.

While the overall incidence of serious adverse events was similar between the toripalimab and placebo groups, there was a higher occurrence of immune-related adverse events and infusion reactions in the toripalimab group, suggesting a manageable but distinct safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toripalimab or placebo plus chemotherapy as first-line treatment in advanced nasopharyngeal carcinoma: a multicenter randomized phase 3 trial. Mai, HQ., Chen, QY., Chen, D., et al.[2022]

In a study of 22 patients with metastatic nasopharyngeal carcinoma, the TXP chemotherapy regimen resulted in a 72% overall clinical response rate, with 63% achieving partial remission and 9% complete remission.

The TXP regimen demonstrated a median overall survival of 14 months and a 1-year survival rate of 68%, while the main side effects were manageable myelosuppression, indicating that the treatment is both effective and safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined chemotherapy with cisplatin, docetaxel and capecitabine for metastatic nasopharyngeal carcinoma: a retrospective analysis. Chen, SZ., Chen, XM., Ding, Y., et al.[2018]

The triple combination therapy of gemcitabine, apatinib, and toripalimab (GAT) showed a high objective response rate of 90.2% in 41 patients with recurrent/metastatic nasopharyngeal carcinoma, indicating strong antitumor activity.

While GAT therapy was effective, it also resulted in significant adverse events, with 56.1% of patients experiencing grade 3 or 4 side effects, including a notable risk of nasopharyngeal necrosis, particularly in patients with a history of repeated radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine combined with apatinib and toripalimab in recurrent or metastatic nasopharyngeal carcinoma. You, R., Zou, X., Ding, X., 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 855 patients with locoregionally advanced nasopharyngeal carcinoma, the induction regimens of docetaxel plus cisplatin and 5-fluorouracil (TPF) and docetaxel plus cisplatin (TP) showed significantly better 10-year overall survival compared to the cisplatin plus 5-fluorouracil (PF) regimen.

The TPF regimen not only improved survival outcomes but also maintained a manageable toxicity profile, with the PF regimen exhibiting the lowest severe toxicities, suggesting a balance between efficacy and safety in treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Toxicity of Three Induction Chemotherapy Regimens in Locoregionally Advanced Nasopharyngeal Carcinoma: Outcomes of 10-Year Follow-Up. Peng, H., Chen, B., He, S., et al.[2022]

In a study of 222 patients with locoregionally advanced nasopharyngeal carcinoma, neoadjuvant chemotherapy with gemcitabine (GEM) and docetaxel plus cisplatin (TP) showed similar overall survival and progression-free survival rates after 5 years, indicating both regimens are effective treatment options.

While both treatment regimens had comparable clinical outcomes, patients receiving TP experienced less severe thrombocytopenia but more severe leucopenia and neutropenia compared to those receiving GEM, highlighting differences in safety profiles between the two chemotherapy combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of neoadjuvant chemotherapy with gemcitabine versus docetaxel plus cisplatin in locoregionally advanced nasopharyngeal carcinoma: a propensity score matching analysis. Liu, T., Sun, Q., Chen, J., et al.[2022]

In a phase 3 trial involving 263 patients with recurrent or metastatic nasopharyngeal carcinoma, the combination of camrelizumab with gemcitabine and cisplatin significantly improved progression-free survival compared to placebo, with a median of 9.7 months versus 6.9 months, indicating its potential as an effective first-line treatment.

While the treatment was associated with common adverse events like decreased white blood cell and neutrophil counts, serious adverse events occurred in 44% of patients receiving camrelizumab, suggesting a need for careful monitoring, especially since treatment-related deaths were reported in 4% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Camrelizumab versus placebo in combination with gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (CAPTAIN-1st): a multicentre, randomised, double-blind, phase 3 trial. Yang, Y., Qu, S., Li, J., et al.[2022]

In a phase II study involving 190 patients with recurrent or metastatic nasopharyngeal carcinoma (NPC), the PD-1 inhibitor toripalimab showed an objective response rate (ORR) of 20.5%, with a median duration of response of 12.8 months, indicating its potential efficacy in this challenging patient population.

A significant correlation was found between a ≥ 50% decrease in plasma Epstein-Barr virus (EBV) DNA after 28 days of treatment and a better response to toripalimab, with an ORR of 48.3% in these patients, suggesting that monitoring EBV levels could help predict treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, Safety, and Correlative Biomarkers of Toripalimab in Previously Treated Recurrent or Metastatic Nasopharyngeal Carcinoma: A Phase II Clinical Trial (POLARIS-02). Wang, FH., Wei, XL., Feng, J., et al.[2023]

In a phase II trial involving 25 patients with recurrent nasopharyngeal carcinoma, toripalimab combined with intensity-modulated radiotherapy (IMRT) resulted in a high overall response rate of 79.2% and disease control in 95.8% of patients at 3 months post-treatment.

The treatment was found to be tolerable, with low incidences of severe acute side effects, although some patients experienced late severe complications such as nasopharyngeal wall necrosis (28.0%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toripalimab plus intensity-modulated radiotherapy for recurrent nasopharyngeal carcinoma: an open-label single-arm, phase II trial. Hua, Y., You, R., Wang, Z., et al.[2022]

In a comparison of anti-PD-1 drugs for recurrent/metastatic nasopharyngeal carcinoma (RM-NPC), camrelizumab showed the highest objective response rate (34.1%) among second-line therapies, while first-line nivolumab achieved a 40% response rate, indicating its effectiveness in treating this cancer.

Nivolumab and pembrolizumab demonstrated the best safety profiles for managing adverse events, particularly for lower-grade side effects, while camrelizumab combined with chemotherapy resulted in a significantly higher response rate (90.9%) compared to chemotherapy alone (64.1%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative safety and efficacy of anti-PD-1 monotherapy, chemotherapy alone, and their combination therapy in advanced nasopharyngeal carcinoma: findings from recent advances in landmark trials. Lv, JW., Li, JY., Luo, LN., et al.[2020]

In a phase 2 trial involving 42 patients with unresectable locally advanced oesophageal squamous cell carcinoma, the combination of toripalimab with chemoradiotherapy resulted in a 62% complete response rate after 3 months, indicating promising efficacy for this treatment approach.

The treatment was generally well-tolerated, with a 1-year overall survival rate of 78.4% and a median duration of response of 12.1 months, although lymphopenia was a common adverse effect, affecting 86% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toripalimab combined with definitive chemoradiotherapy in locally advanced oesophageal squamous cell carcinoma (EC-CRT-001): a single-arm, phase 2 trial. Zhu, Y., Wen, J., Li, Q., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06592599

Study Details | NCT06592599 | Gemcitabine + Docetaxel + ... Patients will receive three q 21-day cycles of gemcitabine 1000 mg/m2 plus docetaxel 75 mg/m2 plus toripalimab 240 mg, followed by radiation to 70 Gy plus ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12479438/

PD-1 inhibitor combined with TPF induction chemotherapy in ... The efficacy of PD-1 inhibitors in the induction therapy of locally advanced nasopharyngeal carcinoma (LA-NPC) remains unclear.

3. withpower.com withpower.com/trial/phase-2-carcinoma-8-2024-59411

Gemcitabine + Docetaxel + Toripalimab for ... In a study of 22 patients with metastatic nasopharyngeal carcinoma, the TXP chemotherapy regimen resulted in a 72% overall clinical response rate, with 63% ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2666379124005263

A phase 2 trial of gemcitabine plus toripalimab for cisplatin ... This phase 2 trial ( NCT04405622 ) evaluated the efficacy and safety of gemcitabine and toripalimab in previously untreated patients with recurrent or ...

5. esmoopen.com esmoopen.com/article/S2059-7029(25)01632-1/fulltext

Consensus statement on the multidisciplinary treatment of ... This study aims to establish a multidisciplinary consensus on the treatment of nasopharyngeal carcinoma (NPC) in China, with a particular ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S1570180825001332

Efficacy and safety of PD-1/PD-L1 inhibitors for relapsed ... The trial group showed higher complete response (CR, RR=1.40, 95 %CI 1.08–1.81, P = 0.01) and objective response rates (ORR, RR=1.16, 95 %CI ...

7. cell.com cell.com/cell-reports-medicine/fulltext/S2666-3791(24)00526-3

A phase 2 trial of gemcitabine plus toripalimab for cisplatin ... No treatment-related fatalities occurred, with the most frequent adverse events being headache and nausea. The ORR was 61.9%, coupled with a ...