Nasopharyngeal CarcinomaPhase 1/2NCT05341193
PD-1 Blockade and Bevacizumab Replace Cisplatin in Locoregionally Advanced Nasopharyngeal Carcinoma
A Phase 1/2 study testing Bevacizumab+Toripalimab+gemcitabine, adjuvant with Bevacizumab and Toripalimab and Bevacizumab+Toripalimab+gemcitabine, adjuvant with Toripalimab in people with Nasopharyngeal Carcinoma, run by Sun Yat-sen University at 1 site in China.
Trial summary
At present, the treatment regimen of locally advanced nasopharyngeal carcinoma still needs to be further improved, and the focus of improvement lies in "replacing cisplatin with high-efficiency and low-toxicity treatment regimen". Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Nasopharyngeal Carcinoma
- What is being tested?
- Bevacizumab+Toripalimab+gemcitabine, adjuvant with Bevacizumab and Toripalimab and Bevacizumab+Toripalimab+gemcitabine, adjuvant with Toripalimab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteChina
- Study dates
- 30 Apr 2022to 30 Dec 2025
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Voluntary participation with Written informed consent.
- Age ≥ 18 years and ≤ 65 years.
- Histologically confirmed with Nonkeratinizing carcinoma of the nasopharynx (differentiated or undifferentiated type).
- Original clinical staged as III-IVa (according to the 8th AJCC edition).
- Stage III patients should meet the criteria of EBV DNA≥4000 cps/ml.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.
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- Patients must have adequate organ function:
- White blood cell count (WBC)≥4.0×109 /L, Hemoglobin ≥ 90g/L, Platelet count ≥100×109/L.
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×upper limit of normal (ULN),serum total bilirubin (TBIL) ≤2.0 times the upper limit of normal (ULN) .
- Adequate renal function: creatinine clearance rate≥60 ml/min or Creatinine ≤1.5× upper limit of normal value.
- INR, APTT≤1.5 x ULN.
Who cannot join
- Subjects with recurrent or metastatic nasopharyngeal carcinoma.
- Histologically or cytologically confirmed with keratinizing squamous cell carcinoma of the nasopharynx.
- Prior therapy with systemic therapy for nasopharyngeal carcinoma.
- Prior exposure to immune checkpoint inhibitors,including anti-PD-1, anti-PD-L1, anti-CTLA-4 antibodies.
- Prior exposure to antiangiogenic agents.
- Tumor invasion to the intracranial with clinical symptoms accompanied by cerebral edema, requiring hormone therapy.
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- Any grade ≥2 bleeding event (according to CTCAE 5.0) occurred within 4 weeks prior to enrollment.
- Subjects with an active, known or suspected autoimmune disease.
- Subjects with clinically significant cardiovascular and cerebrovascular diseases.
- Subjects with high blood pressure who cannot be controlled well with antihypertensive drugs.
- Subjects with previous digestive tract bleeding history within 3 months or evident gastrointestinal bleeding tendency.
- Subjects with arterial / venous thrombosis events occurred within 6 months of the first dose.
- Women in the period of pregnancy, lactation, or reproductive without effective contraceptive measures.
- Seropositivity for human immunodeficiency virus (HIV).
- Known history of other malignancies (except cured basal cell carcinoma or carcinoma in situ of the cervix).
Trial locations and contacts
1 site in 1 country.
China1 site
Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center
Guangzhou, Guangdong, 510060
Ming-Yuan Chen, MD,PhD, 86-20-8734-2422, chenmy@sysucc.org.cn
About this study
Official title: PD-1 Inhibitor and Bevacizumab Replace Cisplatin in Induction, Concurrent, and/or Adjuvant Therapy for High-risk Locoregionally Advanced Nasopharyngeal Carcinoma.
At present, the treatment regimen of locally advanced nasopharyngeal carcinoma still needs to be further improved, and the focus of improvement lies in "replacing cisplatin with high-efficiency and low-toxicity treatment regimen". Considering the synergistic effect among radiotherapy, immunotherapy and anti-angiogenesis therapy, we chose PD-1 inhibitor combined with bevacizumab to replace cisplatin chemotherapy.
Read the detailed description
We plan to use PD-1 inhibitor combined with bevacizumab to replace cisplatin (induction + concurrent ± adjuvant) in patients with locally advanced nasopharyngeal carcinoma. Considering the safety of the original study, we will set up two groups for the adjuvant treatment stage: one group will only use PD-1 inhibitor at the adjuvant treatment stage (low risk group), and the other group will use bevacizumab +PD-1 inhibitor combined treatment (high risk group). Once the efficacy and safety of this protocol are confirmed, it may provide a new treatment option for locally advanced nasopharyngeal carcinoma.
- Conditions
- Nasopharyngeal Carcinoma
- Being tested
- Bevacizumab+Toripalimab+gemcitabine, adjuvant with Bevacizumab and Toripalimab, Bevacizumab+Toripalimab+gemcitabine, adjuvant with Toripalimab
- Keywords
- antiangiogenesis, immunotherapy, Locoregionally Advanced Nasopharyngeal Carcinoma
- Medical subject headings
- Nasopharyngeal Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bevacizumab+Toripalimab+gemcitabine, adjuvant with Bevacizumab and ToripalimabDrug
Induction therapy:
Toripalimab (240mg iv drip)+Bevacizumab (7.5mg/kg iv drip)+gemcitabine (1,000 mg/m2), every 3 weeks for 3 cycles before radiotherapy.
Concurrent therapy:
Toripalimab (240mg iv drip)+Bevacizumab (7.5mg/kg iv drip), every 3 weeks for 2 cycles during radiotherapy.
Adjuvant therapy:
Toripalimab (240mg iv drip)+Bevacizumab (7.5mg/kg iv drip), every 3 weeks for 1 year after radiotherapy.
Radiation:
Intensity-modulated radiotherapy.
Bevacizumab+Toripalimab+gemcitabine, adjuvant with ToripalimabDrug
Induction therapy:
Toripalimab (240mg iv drip)+Bevacizumab (7.5mg/kg iv drip)+gemcitabine (1,000 mg/m2), every 3 weeks for 3 cycles before radiotherapy.
Concurrent therapy:
Toripalimab (240mg iv drip)+Bevacizumab (7.5mg/kg iv drip), every 3 weeks for 2 cycles during radiotherapy.
Adjuvant therapy:
Toripalimab (240mg iv drip), every 3 weeks for 1 year after radiotherapy.
Radiation:
Intensity-modulated radiotherapy.
| Study group | Role | What they receive |
|---|---|---|
| low risk | Experimental | Patients will receive induction therapy with toripalimab plus bevacizumab and gemcitabine every 3 weeks for 3 cycles before radiotherapy, then followed by IMRT and concurrent therapy with toripalimab plus bevacizumab for 2 cycles, then followed by adjuvant therapy with toripalimab every 3 weeks for a maximum of 1 year after radiotherapy. Receives: Drug: Bevacizumab+Toripalimab+gemcitabine, adjuvant with Toripalimab |
| high risk | Experimental | Patients will receive induction therapy with toripalimab plus bevacizumab and gemcitabine every 3 weeks for 3 cycles before radiotherapy, then followed by IMRT and concurrent therapy with toripalimab plus bevacizumab for 2 cycles, then followed by adjuvant therapy with toripalimab and bevacizumab every 3 weeks for a maximum of 1 year after radiotherapy. Receives: Drug: Bevacizumab+Toripalimab+gemcitabine, adjuvant with Bevacizumab and Toripalimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
grade ≥3 nasopharyngeal necrosis or hemorrhage
Incidence of nasopharyngeal necrosis or massive hemorrhage (grade ≥3).
Grade ≥3 hemorrhage: Grade 3, Transfusion indicated; invasive intervention indicated; hospitalization. Grade 4, Life-threatening consequences; urgent intervention indicated (e.g., tracheotomy or intubation). Grade 5, death.
Grade ≥3 nasopharyngeal necrosis: Grade 3, Severe pain; unable to adequately aliment or hydrate orally; limiting self care ADL. Grade 4, Life-threatening consequences; urgent intervention indicated.
Grade 5, death.
Measured: At the end of each cycle (each cycle is 21 days)
Secondary outcomes (6)
Objective response rate
The proportion of patients whose tumors shrink to a certain size and maintain such size for a certain period of time, including patients with complete response (CR) and partial response (PR).
Measured: 3 weeks after indution therapy; 3 months after concurrent therapy
Progression-free survival
Progress-free survival is calculated from the date of enrollment to the date of the first progression at any site or death from any cause or censored at the date of the last follow-up.
Measured: 3 year
Overall survival
Overall survival is calculated from the date of enrollment to the date of the death from any cause or censored at the date of the last follow-up.
Measured: 3 year
Locoregional failure-free survival (LRRFS)
Defined as the time from registration to local or regional relapse, or death from any cause.
Measured: 3 year
Distant metastasis-free survival (DMFS)
Defined as the time from registration to distant metastasis, or death from any cause.
Measured: 3 year
Incidence rate of adverse events (AEs)
Analysis of acute and late adverse events (AEs) are evaluated. Numbers of patients of treatment-related adverse events (acute toxicity) and late radiation toxicities were assessed by CTCAE v5.0.
Measured: 3 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2022
- Study start30 Apr 2022 (estimated)
- Primary completion30 Apr 2023 (estimated)
- Study completion30 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Nasopharyngeal CarcinomaStudies of the same condition, open and under way.
- More trials run by Sun Yat-sen UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 32 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Collaborators
- The First Affiliated Hospital of Nanchang University
- Responsible party
- Principal investigator, Ming-Yuan Chen, Sun Yat-sen University
- Investigators
- Ming-yuan Chen, MD, PhD, Study chair, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05341193
- Sponsor's protocol ID
- SYSUCC-CMY-2022-0416
- Status last verified
- Apr 2022
- First submitted
- 18 Apr 2022
- Last updated
- 22 Apr 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PD-1 Inhibitor and Bevacizumab Replace Cisplatin in Induction, Concurrent, and/or Adjuvant Therapy for High-risk Locoregionally Advanced Nasopharyngeal Carcinoma.
- ClinicalTrials.gov ID
- NCT05341193
- Acronym / sponsor ID
- SYSUCC-CMY-2022-0416
- Conditions
- Nasopharyngeal Carcinoma
- Keywords
- antiangiogenesis, immunotherapy, Locoregionally Advanced Nasopharyngeal Carcinoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 32 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Collaborators
- The First Affiliated Hospital of Nanchang University
- Study start
- 30 Apr 2022 (estimated)
- Primary completion
- 30 Apr 2023 (estimated)
- Study completion
- 30 Dec 2025 (estimated)
- First posted
- 22 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
At present, the treatment regimen of locally advanced nasopharyngeal carcinoma still needs to be further improved, and the focus of improvement lies in "replacing cisplatin with high-efficiency and low-toxicity treatment regimen". Considering the synergistic effect among radiotherapy, immunotherapy and anti-angiogenesis therapy, we chose PD-1 inhibitor combined with bevacizumab to replace cisplatin chemotherapy.
Detailed description
We plan to use PD-1 inhibitor combined with bevacizumab to replace cisplatin (induction + concurrent ± adjuvant) in patients with locally advanced nasopharyngeal carcinoma. Considering the safety of the original study, we will set up two groups for the adjuvant treatment stage: one group will only use PD-1 inhibitor at the adjuvant treatment stage (low risk group), and the other group will use bevacizumab +PD-1 inhibitor combined treatment (high risk group). Once the efficacy and safety of this protocol are confirmed, it may provide a new treatment option for locally advanced nasopharyngeal carcinoma.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| low risk | Experimental | Drug: Bevacizumab+Toripalimab+gemcitabine, adjuvant with ToripalimabPatients will receive induction therapy with toripalimab plus bevacizumab and gemcitabine every 3 weeks for 3 cycles before radiotherapy, then followed by IMRT and concurrent therapy with toripalimab plus bevacizumab for 2 cycles, then followed by adjuvant therapy with toripalimab every 3 weeks for a maximum of 1 year after radiotherapy. |
| high risk | Experimental | Drug: Bevacizumab+Toripalimab+gemcitabine, adjuvant with Bevacizumab and ToripalimabPatients will receive induction therapy with toripalimab plus bevacizumab and gemcitabine every 3 weeks for 3 cycles before radiotherapy, then followed by IMRT and concurrent therapy with toripalimab plus bevacizumab for 2 cycles, then followed by adjuvant therapy with toripalimab and bevacizumab every 3 weeks for a maximum of 1 year after radiotherapy. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Voluntary participation with Written informed consent.
- Age ≥ 18 years and ≤ 65 years.
- Histologically confirmed with Nonkeratinizing carcinoma of the nasopharynx (differentiated or undifferentiated type).
- Original clinical staged as III-IVa (according to the 8th AJCC edition).
- Stage III patients should meet the criteria of EBV DNA≥4000 cps/ml.
Key exclusion criteria (15 listed)
- Subjects with recurrent or metastatic nasopharyngeal carcinoma.
- Histologically or cytologically confirmed with keratinizing squamous cell carcinoma of the nasopharynx.
- Prior therapy with systemic therapy for nasopharyngeal carcinoma.
- Prior exposure to immune checkpoint inhibitors,including anti-PD-1, anti-PD-L1, anti-CTLA-4 antibodies.
- Prior exposure to antiangiogenic agents.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bevacizumab+Toripalimab+gemcitabine, adjuvant with Bevacizumab and ToripalimabInduction therapy: Toripalimab (240mg iv drip)+Bevacizumab (7.5mg/kg iv drip)+gemcitabine (1,000 mg/m2), every 3 weeks for 3 cycles before radiotherapy. Concurrent therapy: Toripalimab (240mg iv drip)+Bevacizumab (7.5mg/kg iv drip), every 3 weeks for 2 cycles during radiotherapy. Adjuvant therapy: Toripalimab (240mg iv drip)+Bevacizumab (7.5mg/kg iv drip), every 3 weeks for 1 year after radiotherapy. Radiation: Intensity-modulated radiotherapy. | Drug | high risk |
| Bevacizumab+Toripalimab+gemcitabine, adjuvant with ToripalimabInduction therapy: Toripalimab (240mg iv drip)+Bevacizumab (7.5mg/kg iv drip)+gemcitabine (1,000 mg/m2), every 3 weeks for 3 cycles before radiotherapy. Concurrent therapy: Toripalimab (240mg iv drip)+Bevacizumab (7.5mg/kg iv drip), every 3 weeks for 2 cycles during radiotherapy. Adjuvant therapy: Toripalimab (240mg iv drip), every 3 weeks for 1 year after radiotherapy. Radiation: Intensity-modulated radiotherapy. | Drug | low risk |
Primary outcome
grade ≥3 nasopharyngeal necrosis or hemorrhage
Time frame: At the end of each cycle (each cycle is 21 days)
Incidence of nasopharyngeal necrosis or massive hemorrhage (grade ≥3). Grade ≥3 hemorrhage: Grade 3, Transfusion indicated; invasive intervention indicated; hospitalization. Grade 4, Life-threatening consequences; urgent intervention indicated (e.g., tracheotomy or intubation). Grade 5, death. Grade ≥3 nasopharyngeal necrosis: Grade 3, Severe pain; unable to adequately aliment or hydrate orally; limiting self care ADL. Grade 4, Life-threatening consequences; urgent intervention indicated. Grade 5, death.
6 secondary outcomes
Objective response rate
Time frame: 3 weeks after indution therapy; 3 months after concurrent therapy
Progression-free survival
Time frame: 3 year
Overall survival
Time frame: 3 year
Locoregional failure-free survival (LRRFS)
Time frame: 3 year
Distant metastasis-free survival (DMFS)
Time frame: 3 year
Incidence rate of adverse events (AEs)
Time frame: 3 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ming-yuan Chen, MD, PhD study chair
Sun Yat-sen University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Bevacizumab+Toripalimab+gemcitabine, adjuvant with Bevacizumab and Toripalimab and Bevacizumab+Toripalimab+gemcitabine, adjuvant with Toripalimab in people with Nasopharyngeal Carcinoma, run by Sun Yat-sen University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ming-Yuan Chen, MD, PhD (86-20-8734-3361, chmingy@mail.sysu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
grade ≥3 nasopharyngeal necrosis or hemorrhage (time frame: At the end of each cycle (each cycle is 21 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Apr 2022.