Back to results

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

Primary Purpose

Nasopharyngeal Carcinoma

Status

Not yet recruiting

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

Bevacizumab+Toripalimab+gemcitabine, adjuvant with Bevacizumab and Toripalimab

Bevacizumab+Toripalimab+gemcitabine, adjuvant with Toripalimab

About this trial

This is an interventional treatment trial for Nasopharyngeal Carcinoma focused on measuring antiangiogenesis, immunotherapy, Locoregionally Advanced Nasopharyngeal Carcinoma

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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:
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:

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).

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

low risk

high risk

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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).

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.

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.

Locoregional failure-free survival (LRRFS)

Defined as the time from registration to local or regional relapse, or death from any cause.

Distant metastasis-free survival (DMFS)

Defined as the time from registration to distant metastasis, or death from any cause.

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.

Full Information

NCT ID

NCT05341193

First Posted

April 18, 2022

Last Updated

April 18, 2022

Sponsor

Sun Yat-sen University

Collaborators

The First Hospital of Nanchang

1. Study Identification

Unique Protocol Identification Number

NCT05341193

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2022

Overall Recruitment Status

Not yet recruiting

Study Start Date

April 30, 2022 (Anticipated)

Primary Completion Date

April 30, 2023 (Anticipated)

Study Completion Date

December 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Sun Yat-sen University

Collaborators

The First Hospital of Nanchang

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Nasopharyngeal Carcinoma

Keywords

antiangiogenesis, immunotherapy, Locoregionally Advanced Nasopharyngeal Carcinoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

32 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

low risk

Arm Type

Experimental

Arm Description

Arm Title

high risk

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Bevacizumab+Toripalimab+gemcitabine, adjuvant with Bevacizumab and Toripalimab

Intervention Description

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

Intervention Name(s)

Bevacizumab+Toripalimab+gemcitabine, adjuvant with Toripalimab

Intervention Description

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.

Primary Outcome Measure Information:

Title

grade ≥3 nasopharyngeal necrosis or hemorrhage

Description

Time Frame

At the end of each cycle (each cycle is 21 days)

Secondary Outcome Measure Information:

Title

Objective response rate

Description

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).

Time Frame

3 weeks after indution therapy; 3 months after concurrent therapy

Title

Progression-free survival

Description

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.

Time Frame

3 year

Title

Overall survival

Description

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.

Time Frame

3 year

Title

Locoregional failure-free survival (LRRFS)

Description

Defined as the time from registration to local or regional relapse, or death from any cause.

Time Frame

3 year

Title

Distant metastasis-free survival (DMFS)

Description

Defined as the time from registration to distant metastasis, or death from any cause.

Time Frame

3 year

Title

Incidence rate of adverse events (AEs)

Description

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.

Time Frame

3 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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).

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Ming-Yuan Chen, MD, PhD

Phone

86-20-8734-3361

chmingy@mail.sysu.edu.cn

First Name & Middle Initial & Last Name or Official Title & Degree

Xi Ding, MD

Phone

86-19880836260

dingxi@sysucc.org.cn

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ming-yuan Chen, MD, PhD

Organizational Affiliation

Sun Yat-sen University

Official's Role

Study Chair

Facility Information:

Facility Name

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

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510060

Country

China

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ming-Yuan Chen, MD,PhD

Phone

86-20-8734-2422

chenmy@sysucc.org.cn

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs