Toripalimab, Endostar Combined With Radiotherapy and Chemotherapy for Nasopharyngeal Carcinoma

June 24, 2020 updated by: min kang, First Affiliated Hospital of Guangxi Medical University

Randomized Controlled, Multicenter Phase II Clinical Research of Toripalimab (PD-1 Inhibitor) and Endostar Combined With Radiotherapy and Chemotherapy in the Treatment of High-risk Locally Advanced Nasopharyngeal Carcinoma

This study is to investigate the efficacy and safety of the induction chemotherapy + concurrent chemoradiotherapy（CCRT）combined with toripalimab and endostar treatment, in comparison with the induction chemotherapy + concurrent chemoradiotherapy（CCRT）, in treating locally advanced high-risk nasopharyngeal carcinoma

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

GP-induced chemotherapy combined with concurrent chemoradiotherapy is the standard treatment for the locally advanced nasopharyngeal carcinoma recommended by the guidelines. However, the prognosis for T4 and/or N3 nasopharyngeal carcinoma is still poor, with the 3-year PFS of about 70%. Therefore, it is of great importance to improve the prognosis of patients with locally advanced high-risk nasopharyngeal carcinoma. Immunotherapy has been an emerging treatment method for tumors in recent years. Compared with the chemotherapy, immunotherapy has less adverse reactions, and the effects could last longer, significantly improving the prognosis and patients' quality of life. Endostar, as a VEGFR inhibitor, has good safety in treating nasopharyngeal carcinoma. Related data have shown that PD-1 and Endostar exert synergistic antitumor effects in a mouse model of lung cancer. A Phase II multi-center clinical study from our center has shown that, for patients with locally advanced low-risk nasopharyngeal carcinoma, all the 3-year OS, PFS, and DMFS for the radiotherapy combined with Endostar group were superior to the concurrent chemoradiotherapy group, and the combination of radiotherapy and Endostar lead to significantly reduced adverse effects. In clinical studies concerning other solid tumors, it has also been observed that the PD-1 inhibitors combined with VEGFR inhibitors could significantly improve the efficacy, and achieve synergistic effects. Therefore, A Phase II，randomized, prospective, multicentric clinical trail was conducted to compare the efficacy and safety of induction chemotherapy and the concurrent chemoradiotherapy plus Endostar and PD-1, followed by PD-1 treatment for half a year compared with the induction chemotherapy and the concurrent chemoradiotherapy for the T4 and/or N3 nasopharyngeal carcinoma.

Study Type

Interventional

Enrollment (Anticipated)

106

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Min Kang, Ph.D
  • Phone Number: 86-771-5356509
  • Email: km1019@163.com

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. With ECOG score 0-1.
  2. Subjective aged 18-65 years, male or non-pregnant female.
  3. Pathologically diagnosed as nasopharyngeal non-keratinizing carcinoma (differentiated or undifferentiated, i.e., the WHO type II or III).
  4. Stage IVa (8th AJCC/UICC stage) T4 and/or N3, untreated patients with nasopharyngeal carcinoma.
  5. Agreeing to provide previously stored tumor tissue samples or perform biopsy to collect tumor tissues, which were sent to the central laboratory for the PD-L1 IHC test.
  6. Hematology: white blood cells ≥ 4000 /μL; neutrophils ≥ 2000 /μL; hemoglobin ≥ 9 g/dL; and platelets ≥ 100000 /μL.
  7. Liver function: ALT and AST lower than the 1.5 times (1.5 × ) the upper limits of normal (ULN); and total bilirubin < 1.5 × ULN.
  8. Renal function: serum creatinine < 1.5 × ULN.
  9. Patients signing the informed consents, and willing and able to follow the study plan (visit and treatment plan), laboratory tests, and other research procedures.

Exclusion criteria:

  1. Patients with nasopharyngeal carcinoma with recurrence and distant metastasis.
  2. Pathologically diagnosed as keratinizing squamous cell carcinoma (WHO classification type I).
  3. Patients who had undergone radiotherapy or systemic chemotherapy.
  4. Pregnant or breastfeeding females, or females in fertility period while with no effective contraceptive measures.
  5. Positive for HIV.
  6. Having suffered from other malignant tumors (except for the cured basal cell carcinoma or cervical carcinoma in situ).
  7. Having been treated with inhibitors of immune regulatory points (i.e., CTLA-4, PD-1, PD-L1, etc.).
  8. With complications needing long-term application of immunosuppressive drugs, or systemic or local application of corticosteroids with immunosuppressive doses of comorbidities.
  9. Patients with immunodeficiency diseases, or a history of organ transplantation (including but not limited to: interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, nephritis, hyperthyroidism, hypothyroidism; patients suffering from vitiligo, or asthma in childhood completely relieved, with no need of any intervention after adulthood could be included; and patients with asthma requiring bronchodilators for medical intervention could not be included).
  10. With excessive usage of glucocorticoids within 4 weeks.
  11. Whose laboratory examination values that did not meet the relevant standards within 7 days before participating in the research.
  12. Patients with markedly reduced heart, liver, lung, kidney and/or bone marrow functions.
  13. With serious and uncontrolled medical diseases and infections.
  14. Using other test drugs or in other clinical trials.
  15. Refusing or failing to sign the informed consent to participate in the trial.
  16. With other treatment contraindications.
  17. With personality or mental illness, with no or limited civil capacity.
  18. Positive for hepatitis B surface antigen (HBsAg), and peripheral blood hepatitis B virus deoxyribonucleic acid (HBV DNA) ≥ 1000 cps/mL.
  19. Patients positive for the HCV antibody test could only be included in this study with the negative results from the HCV RNA polymerase chain reaction test.
  20. Unable to cooperate with regular follow-up due to psychological, social, family and geographical reasons.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: IC＋CCRT＋Toripalimab＋Endostar
Three cycles of induction chemotherapy with GP regimen (Q3W): Gem 1000 mg/m2 d1,8; DDP 80mg/m2 d1, Q3W; IMRT (6-7 weeks, 5 times each week) combined with cisplatin for 2-3 cycles (Q3W): DDP 100 mg/m2, Q3W, 2-3 cycles; IMRT: GTVnx 70-74Gy/30-33f, 5d/w, 6-7 w; Toripalimab: 240 mg, Q3W, starting on D1, for totally 12 cycles; Endostar: 7.5 mg/m2/d, continuous intravenous pumping for 10 days, Q3W, starting on D1, for totally 5 cycles.
Drug: Toripalimab, Endostar Combined With Radiotherapy and Chemotherapy
Toripalimab: 240 mg, Q3W, starting on D1, for totally 12 cycles Endostar: 7.5 mg/m2/d, continuous intravenous pumping for 10 days, Q3W, starting on D1, for totally 5 cycles
Other Names:
  • JS001
Active Comparator: IC＋CCRT
Three cycles of induction chemotherapy with GP regimen (Q3W): Gem 1000 mg/m2 d1,8; DDP 80mg/m2 d1, Q3W; IMRT (6-7 weeks, 5 times each week) combined with cisplatin for 2-3 cycles (Q3W): DDP 100 mg/m2, Q3W, 2-3 cycles; IMRT: GTVnx 70-74Gy/30-33f, 5d/w, 6-7 w.
Drug: IC＋CCRT
IC＋CCRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
progression-free survival, PFS
Time Frame: 3 years
calculated from the date of randomisation to the date of the documented local or regional relapse, distant metastasis, or death from any cause, whichever occurred first. distant failure, or death from any cause, whichever occurred first.
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival，OS
Time Frame: 3 years
the time from random assignment to death from any cause or censored at the date of last follow-up.
3 years
locoregional relapse-free Survival, LRFS
Time Frame: 3 years
the time from random assignment to local or regional relapse.
3 years
Distant metastasis-free survival,DMFS
Time Frame: 3 years
calculated from date of randomisation to the first distant failure
3 years
Overall response rate (ORR)
Time Frame: 3 months
complete response (CR) + partial response (PR)
3 months
adverse events (AEs) and severe adverse events (SAE)
Time Frame: 3 years
graded according to NCI CTCAE 5.0
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

First Affiliated Hospital of Guangxi Medical University

Collaborators

Zhejiang Cancer Hospital
Xiangya Hospital of Central South University
Shandong Cancer Hospital and Institute
Jiangxi Provincial Cancer Hospital
Wuhan Union Hospital, China
The Affiliated Hospital Of Guizhou Medical University
Guilin Medical College
LiuZhou People's Hospital
Fourth Affiliated Hospital of Guangxi Medical University
Affiliated Hospital of North Sichuan Medical College

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

June 1, 2020

Primary Completion (Anticipated)

June 1, 2024

Study Completion (Anticipated)

June 1, 2026

Study Registration Dates

First Submitted

June 23, 2020

First Submitted That Met QC Criteria

June 24, 2020

First Posted (Actual)

June 25, 2020

Study Record Updates

Last Update Posted (Actual)

June 25, 2020

Last Update Submitted That Met QC Criteria

June 24, 2020

Last Verified

June 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FirstGuangxiMU1

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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