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

NCT05341193 | Unknown Phase 1

• 1 other identifier: SYSUCC-CMY-2022-0416
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Nasopharyngeal Carcinoma

Keywords

antiangiogenesis; immunotherapy; Locoregionally Advanced Nasopharyngeal Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Objective response rate

  3 weeks after indution therapy; 3 months after concurrent therapy

• Progression-free survival

  3 year

• Overall survival

  3 year

• Locoregional failure-free survival (LRRFS)

  3 year

• Distant metastasis-free survival (DMFS)

  3 year

Study Arms (2)

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.

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.

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

Interventions

Bevacizumab+Toripalimab+gemcitabine, adjuvant with Bevacizumab and Toripalimab 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.

high risk

Bevacizumab+Toripalimab+gemcitabine, adjuvant with Toripalimab 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.

low risk

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• Sun Yat-sen University: lead
• The First Affiliated Hospital of Nanchang University: collaborator

Study Sites (1)

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

Guangzhou, Guangdong, 510060, China

Location

MeSH Terms

Conditions

Nasopharyngeal Carcinoma

Interventions

Adjuvants, Pharmaceutic; Bevacizumab; toripalimab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Pharmaceutic Aids; Pharmaceutical Preparations; Specialty Uses of Chemicals; Chemical Actions and Uses; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Ming-yuan Chen, MD, PhD

  Sun Yat-sen University

  STUDY CHAIR

Central Study Contacts

Ming-Yuan Chen, MD, PhD

CONTACT

86-20-8734-3361; chmingy@mail.sysu.edu.cn

Xi Ding, MD

CONTACT

86-19880836260; dingxi@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief physician, Proffessor

Study Record Dates

• First Submitted: April 18, 2022
• First Posted: April 22, 2022
• Study Start: April 30, 2022
• Primary Completion: April 30, 2023
• Study Completion: December 30, 2025
• Last Updated: April 22, 2022

Record last verified: 2022-04

Locations

CN (1)