PD-1 Blockade and Bevacizumab Replace Cisplatin in Locoregionally Advanced Nasopharyngeal Carcinoma

Nasopharyngeal Carcinoma Clinical Trial

Official title:

PD-1 Inhibitor and Bevacizumab Replace Cisplatin in Induction, Concurrent, and/or Adjuvant Therapy for High-risk Locoregionally Advanced Nasopharyngeal Carcinoma.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05341193
• Other study ID #: SYSUCC-CMY-2022-0416
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: April 30, 2022
• Est. completion date: December 30, 2025

Study information

• Verified date: April 2022
• Source: Sun Yat-sen University
• Contact: Ming-Yuan Chen, MD, PhD
• Phone: 86-20-8734-3361
• Email: chmingy[@]mail.sysu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical 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". Considering the synergistic effect among radiotherapy, immunotherapy and anti-angiogenesis therapy, we chose PD-1 inhibitor combined with bevacizumab to replace cisplatin chemotherapy.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 32
• Est. completion date: December 30, 2025
• Est. primary completion date: April 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Voluntary participation with Written informed consent.

2. Age = 18 years and = 65 years.

3. Histologically confirmed with Nonkeratinizing carcinoma of the nasopharynx (differentiated or undifferentiated type).

4. Original clinical staged as III-IVa (according to the 8th AJCC edition).

5. Stage III patients should meet the criteria of EBV DNA=4000 cps/ml.

6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.

7. Patients must have adequate organ function:

1. White blood cell count (WBC)=4.0×109 /L, Hemoglobin = 90g/L, Platelet count =100×109/L.

2. 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) .

3. Adequate renal function: creatinine clearance rate=60 ml/min or Creatinine =1.5× upper limit of normal value.

4. INR, APTT=1.5 x ULN.

Exclusion Criteria:

1. Subjects with recurrent or metastatic nasopharyngeal carcinoma.

2. Histologically or cytologically confirmed with keratinizing squamous cell carcinoma of the nasopharynx.

3. Prior therapy with systemic therapy for nasopharyngeal carcinoma.

4. Prior exposure to immune checkpoint inhibitors,including anti-PD-1, anti-PD-L1, anti-CTLA-4 antibodies.

5. Prior exposure to antiangiogenic agents.

6. Tumor invasion to the intracranial with clinical symptoms accompanied by cerebral edema, requiring hormone therapy.

7. Any grade =2 bleeding event (according to CTCAE 5.0) occurred within 4 weeks prior to enrollment.

8. Subjects with an active, known or suspected autoimmune disease.

9. Subjects with clinically significant cardiovascular and cerebrovascular diseases.

10. Subjects with high blood pressure who cannot be controlled well with antihypertensive drugs.

11. Subjects with previous digestive tract bleeding history within 3 months or evident gastrointestinal bleeding tendency.

12. Subjects with arterial / venous thrombosis events occurred within 6 months of the first dose.

13. Women in the period of pregnancy, lactation, or reproductive without effective contraceptive measures.

14. Seropositivity for human immunodeficiency virus (HIV).

15. Known history of other malignancies (except cured basal cell carcinoma or carcinoma in situ of the cervix).

Related Conditions & MeSH terms

• Carcinoma
• Nasopharyngeal Carcinoma

Intervention

Drug:
• Bevacizumab+Toripalimab+gemcitabine, adjuvant with Bevacizumab and Toripalimab
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 Toripalimab
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.

Locations

Country	Name	City	State
China	Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center	Guangzhou	Guangdong

Sponsors (2)

Lead Sponsor	Collaborator
Sun Yat-sen University	The First Hospital of Nanchang

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	At the end of each cycle (each cycle is 21 days)
Secondary	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).	3 weeks after indution therapy; 3 months after concurrent therapy
Secondary	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.	3 year
Secondary	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.	3 year
Secondary	Locoregional failure-free survival (LRRFS)	Defined as the time from registration to local or regional relapse, or death from any cause.	3 year
Secondary	Distant metastasis-free survival (DMFS)	Defined as the time from registration to distant metastasis, or death from any cause.	3 year
Secondary	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.	3 year