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

NCT ID: NCT05341193

Last Updated: 2022-04-22

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-04-30
• Study Completion Date: 2025-12-30

Brief 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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

low risk

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.

Group Type: EXPERIMENTAL

Bevacizumab+Toripalimab+gemcitabine, adjuvant with Toripalimab

Intervention Type: DRUG

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.

high risk

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.

Group Type: EXPERIMENTAL

Bevacizumab+Toripalimab+gemcitabine, adjuvant with Bevacizumab and Toripalimab

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The First Affiliated Hospital of Nanchang University

OTHER

Sponsor Role: collaborator

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Ming-Yuan Chen

Chief physician, Proffessor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ming-yuan Chen, MD, PhD

Role: STUDY_CHAIR

Sun Yat-sen University

Locations

Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

Countries

China

Central Contacts

Ming-Yuan Chen, MD, PhD

Role: CONTACT

chmingy@mail.sysu.edu.cn

86-20-8734-3361

Xi Ding, MD

Role: CONTACT

dingxi@sysucc.org.cn

86-19880836260

Facility Contacts

Ming-Yuan Chen, MD,PhD

Role: primary

chenmy@sysucc.org.cn

86-20-8734-2422

Other Identifiers

SYSUCC-CMY-2022-0416

Identifier Type: -

Identifier Source: org_study_id