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Reduced-target Resection After Induction Chemotherapy in Resectable Recurrent Nasopharyngeal Carcinoma

Primary Purpose

Nasopharyngeal Carcinoma, De-escaltion Therapy

Status
Recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Reduced-target resection
Full-target resection
Adjuvant immunotherapy
Sponsored by
Sun Yat-sen University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Nasopharyngeal Carcinoma

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: The recurrence time is more than 6 months from the end of radiotherapy. Histologically confirmed recurrent nasopharyngeal carcinoma. Resectable nasopharyngeal diseases: recurrent T1 (the tumor is confined in nasopharynx, oropharynx and/or nasal cavity without parapharyngeal involvement); recurrent T2 (the tumor is confined in the superficial parapharyngeal spacer and is more than 0.5cm far from the internal carotid artery) and recurrent T3 (the tumor is confined in the base wall of the sphenoid sinus and is more than 0.5cm far from the internal carotid artery and cavernous sinus) (according to the 8th edition of American Joint Committee on Cancer (AJCC) staging system for nasopharyngeal carcinoma). If the tumor invaded the internal carotid artery, or the instance from the internal carotid artery was less than 0.5cm, but the invasion area did not exceed the external edge of the internal carotid artery, the patients could be enrolled after internal carotid artery pretreatment (including internal carotid artery embolization or stent implantation). After 3 cycles induction chemotherapy (Platinum based chemotherapy [gemcitabine/paclitaxel and platinum] and immunotherapy[PD-1/PD-L1 antibody] or a GAP regmen[gemcitabine, Apatinib and immunotherapy[PD-1/PD-L1 antibody]), patients achieved at least PR according to RECIST criteria, and the reduction of pSTV after induction chemotherapy more than 50%. Given written informed consent. Exclusion Criteria: Karnofsky Performance Status (KPS) ≤70. Has severe medical disorder, important organ dysfunction, and/or a substantial history of mental illness. Tumor confined to the roof or the posterior wall of nasopharynx, without expected benefit from reduced-target resection. Unresectable recurrent regional lymph node diseases (recurrent N1-3) with prevertebral fascia, cervical vertebrae, or common/internal carotid artery involvement (according to the 8th edition of AJCC staging system). Clinically diagnosed with metastatic NPC. Has known subjects with other malignant tumors (except for cured skin basal cell carcinoma or cervical carcinoma in situ). Received a systematic or local glucocorticoid therapy within 4 weeks of planned start of study treatment. Suffered from diseases need long-term treatment with immunosuppressive drugs, or required systematic or local glucocorticoid therapy with immunosuppressive doses. Prior therapy with a PD-1, anti-PD-Ligand 1 (PD-L1) or cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) agent. Has active autoimmune disease (e.g., uveitis, enteritis, hepatitis, hypophysitis, nephritis, vasculitis, hyperthyroidism, and asthma requiring bronchodilator therapy). Patients with skin disease that doesn't require systemic treatment (e.g., vitiligo, psoriasis, or alopecia) will be allowed to enroll. Has a known history of human immunodeficiency virus (HIV), has hepatitis B surface antigen (HBsAg) positive with hepatitis B virus (HBV) DNA copy number of ≥1000cps/ml or hepatitis C virus (HCV) antibody positive. Has received a live vaccine within 4 weeks of planned start of study treatment. Pregnancy or breast feeding. Cannot complete regular follow-up.

Sites / Locations

  • Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Reduced-target resection group

Full-target resection group

Arm Description

Patients receive surgery according to pSTV-post-IC and adjuvant immunotherapy.

Patients receive surgery according to pSTV-pre-IC and adjuvant immunotherapy.

Outcomes

Primary Outcome Measures

Overall Survival (OS)
Overall survival is calculated from the date of randomization to the date of death of any cause, censored on the last date of known survival if no death has happened

Secondary Outcome Measures

The incidence of Severe Adverse events
The incidence of severe adverse events was defined as the incidence of grade 3 or worse adverse event, including acute and late toxicities.
Score of survival quality according to the EORTC Quality of Life Questionnaire (QLQ)-C30 (V3.0) overall
The quality of life was assessed per EORTC Quality of Life Questionnaire (QLQ)-C30 (V3.0).
In-field recurrence rate
The rate of recuurence within the Gross Tumor Volume before induction chemotherapy
Progression-free survival (PFS)
Progression-free survival is calculated from the date of randomization to the date of death of any cause or the first progress at any site, censored on the last date of tumor evaluation if no progress has happened.
Loco-regional relapse-free survival (LRRFS)
The event for loco-regional relapse-free survival (LRRFS) was loco-regional recurrence. The duration was calculated from the date of treatment initiation to the date of loco-regional relapse or last follow-up.
Distant metastasis-free survival (DMFS)
The event for distant metastasis-free survival (DMFS) was distant metastasis. The duration was calculated from the date of treatment initiation to the date of distant metastasis or the last follow-up.
The proportion of Internal carotid artery pretreatment
the proportion of the patients who received Internal carotid artery pretreatment (including endoscopic-assisted transcervical protection of the parapharyngeal ICA, embolization, stent implantation and so on).
Surgery-related adverse event
The incidence of surgey-related adverse events, including operative accidents and complications.
Operative resection time
Time from making mucosa incision to completely resecting the tumor.
Estimated blood loss
Blood loss will be measured according to the suction and the weight of wet gauze, and then minus the irrigation.
Progression-free survival after salvage treatment as assessed by the investigator (PFS2)
The time from randomization to second/subsequent disease progression after initiation of new anticancer therapy, or death from any cause, which occurs first.

Full Information

First Posted
May 18, 2023
Last Updated
May 25, 2023
Sponsor
Sun Yat-sen University
Collaborators
First Affiliated Hospital, Sun Yat-Sen University, Nanfang Hospital, Southern Medical University, First People's Hospital of Foshan, Zhongshan People's Hospital, Guangdong, China, Fifth Affiliated Hospital of Guangzhou Medical University
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1. Study Identification

Unique Protocol Identification Number
NCT05877872
Brief Title
Reduced-target Resection After Induction Chemotherapy in Resectable Recurrent Nasopharyngeal Carcinoma
Official Title
Reduced-target Resection Compared With Full-target Resection After Induction Chemotherapy in Resectable Recurrent Nasopharyngeal Carcinoma: a Multicentre, Randomised, Open-label, Phase 3 Trial
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 20, 2023 (Anticipated)
Primary Completion Date
March 30, 2029 (Anticipated)
Study Completion Date
March 30, 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sun Yat-sen University
Collaborators
First Affiliated Hospital, Sun Yat-Sen University, Nanfang Hospital, Southern Medical University, First People's Hospital of Foshan, Zhongshan People's Hospital, Guangdong, China, Fifth Affiliated Hospital of Guangzhou Medical University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
The goal of this clinical trial is to compare efficacy of two different resection extension in patients with resectable recurrent nasopharyngeal carcinoma after induction chemotherapy. The main question it aims to answer is that whether tumor regress areas after induction chemotherapy required complete resection. Patients will be randomly assigned to receive reduced-target resection or full-target resection after induction chemotherapy. Researchers will compare these two groups to see if the efficacy of reduced-target resection is not inferior to full-target resection.
Detailed Description
Induction chemotherapy is often used preoperatively to reduce the size, extent, or stage of the tumor, thereby making the surgery more likely to be successful. However, there are still many patients with marginal recurrence after induction chemotherapy combined with surgery. With the progress of treatment methods, high efficient and low toxicity adjuvant immunotherapy is helpful to kill the minimal residual tumor lesions. Hence, whether complete resection is still necessary for areas with tumor regression after induction chemotherapy needs further investigation. Because of the organs at risk around the nasopharynx, any treatment strategy that can reduce the scope of tumor resection is of great significance. Therefore, by comparing reduced-target resection and full-target resection after induction chemotherapy, we aim to investigate whether reduced-target resection after induction chemotherapy is not inferior to full-target resection, but it greatly reduces the risk and difficulty of surgery. Even if marginal recurrence occurs after reduced-target resection, early intervention can still be performed through closely follow-up, without affecting the overall survival of patients. When patients enroll this study, GTV-pre-IC (Gross Tumor Volume before induction chemotherapy) was defined according to the magentic resonance imaging before induction chemotherapy and GTV-post-IC (Gross Tumor Volume after induction chemotherapy) defined according to the magentic resonance imaging after induction chemotherapy. The pSTV-pre-IC (planing Surgical Tumor Volume before induction chemotherapy) and pSTV-post-IC (planing Surgical Tumor Volume after induction chemotherapy) were the GTV-pre-IC and GTV-post-IC plus an additional 0.5-1.0 cm peripheral mucosa margin and a 2-3 mm basal margin on the surface skull base. Patiens in experiment group will receive reduced-target resection, which resection extension is according to pSTV-post-IC. While patients in control group will receive full-target resection, which is according to pSTV-pre-IC. After surgery, the acturial resection area was defined as aSTV, which would be used for quality control. If aSTV does not cover pSTV, patients will be excluded in per-protocol set.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nasopharyngeal Carcinoma, De-escaltion Therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
424 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Reduced-target resection group
Arm Type
Experimental
Arm Description
Patients receive surgery according to pSTV-post-IC and adjuvant immunotherapy.
Arm Title
Full-target resection group
Arm Type
Active Comparator
Arm Description
Patients receive surgery according to pSTV-pre-IC and adjuvant immunotherapy.
Intervention Type
Procedure
Intervention Name(s)
Reduced-target resection
Intervention Description
Patients receive surgery according to pSTV-post-IC.
Intervention Type
Procedure
Intervention Name(s)
Full-target resection
Intervention Description
Patients receive surgery according to pSTV-pre-IC.
Intervention Type
Drug
Intervention Name(s)
Adjuvant immunotherapy
Intervention Description
Toripalimab(240 mg d1) continually applied since 1-2 weeks after surgery until confirmed disease progression, death, unacceptable toxicity, withdrawal of consent, investigator decision, or 1 year.
Primary Outcome Measure Information:
Title
Overall Survival (OS)
Description
Overall survival is calculated from the date of randomization to the date of death of any cause, censored on the last date of known survival if no death has happened
Time Frame
3 years
Secondary Outcome Measure Information:
Title
The incidence of Severe Adverse events
Description
The incidence of severe adverse events was defined as the incidence of grade 3 or worse adverse event, including acute and late toxicities.
Time Frame
3 years
Title
Score of survival quality according to the EORTC Quality of Life Questionnaire (QLQ)-C30 (V3.0) overall
Description
The quality of life was assessed per EORTC Quality of Life Questionnaire (QLQ)-C30 (V3.0).
Time Frame
3 years
Title
In-field recurrence rate
Description
The rate of recuurence within the Gross Tumor Volume before induction chemotherapy
Time Frame
3 years
Title
Progression-free survival (PFS)
Description
Progression-free survival is calculated from the date of randomization to the date of death of any cause or the first progress at any site, censored on the last date of tumor evaluation if no progress has happened.
Time Frame
3 years
Title
Loco-regional relapse-free survival (LRRFS)
Description
The event for loco-regional relapse-free survival (LRRFS) was loco-regional recurrence. The duration was calculated from the date of treatment initiation to the date of loco-regional relapse or last follow-up.
Time Frame
3 years
Title
Distant metastasis-free survival (DMFS)
Description
The event for distant metastasis-free survival (DMFS) was distant metastasis. The duration was calculated from the date of treatment initiation to the date of distant metastasis or the last follow-up.
Time Frame
3 years
Title
The proportion of Internal carotid artery pretreatment
Description
the proportion of the patients who received Internal carotid artery pretreatment (including endoscopic-assisted transcervical protection of the parapharyngeal ICA, embolization, stent implantation and so on).
Time Frame
1 Day of surgery
Title
Surgery-related adverse event
Description
The incidence of surgey-related adverse events, including operative accidents and complications.
Time Frame
3 years
Title
Operative resection time
Description
Time from making mucosa incision to completely resecting the tumor.
Time Frame
1 Day of surgery
Title
Estimated blood loss
Description
Blood loss will be measured according to the suction and the weight of wet gauze, and then minus the irrigation.
Time Frame
1 Day of surgery
Title
Progression-free survival after salvage treatment as assessed by the investigator (PFS2)
Description
The time from randomization to second/subsequent disease progression after initiation of new anticancer therapy, or death from any cause, which occurs first.
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: The recurrence time is more than 6 months from the end of radiotherapy. Histologically confirmed recurrent nasopharyngeal carcinoma. Resectable nasopharyngeal diseases: recurrent T1 (the tumor is confined in nasopharynx, oropharynx and/or nasal cavity without parapharyngeal involvement); recurrent T2 (the tumor is confined in the superficial parapharyngeal spacer and is more than 0.5cm far from the internal carotid artery) and recurrent T3 (the tumor is confined in the base wall of the sphenoid sinus and is more than 0.5cm far from the internal carotid artery and cavernous sinus) (according to the 8th edition of American Joint Committee on Cancer (AJCC) staging system for nasopharyngeal carcinoma). If the tumor invaded the internal carotid artery, or the instance from the internal carotid artery was less than 0.5cm, but the invasion area did not exceed the external edge of the internal carotid artery, the patients could be enrolled after internal carotid artery pretreatment (including internal carotid artery embolization or stent implantation). After 3 cycles induction chemotherapy (Platinum based chemotherapy [gemcitabine/paclitaxel and platinum] and immunotherapy[PD-1/PD-L1 antibody] or a GAP regmen[gemcitabine, Apatinib and immunotherapy[PD-1/PD-L1 antibody]), patients achieved at least PR according to RECIST criteria, and the reduction of pSTV after induction chemotherapy more than 50%. Given written informed consent. Exclusion Criteria: Karnofsky Performance Status (KPS) ≤70. Has severe medical disorder, important organ dysfunction, and/or a substantial history of mental illness. Tumor confined to the roof or the posterior wall of nasopharynx, without expected benefit from reduced-target resection. Unresectable recurrent regional lymph node diseases (recurrent N1-3) with prevertebral fascia, cervical vertebrae, or common/internal carotid artery involvement (according to the 8th edition of AJCC staging system). Clinically diagnosed with metastatic NPC. Has known subjects with other malignant tumors (except for cured skin basal cell carcinoma or cervical carcinoma in situ). Received a systematic or local glucocorticoid therapy within 4 weeks of planned start of study treatment. Suffered from diseases need long-term treatment with immunosuppressive drugs, or required systematic or local glucocorticoid therapy with immunosuppressive doses. Prior therapy with a PD-1, anti-PD-Ligand 1 (PD-L1) or cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) agent. Has active autoimmune disease (e.g., uveitis, enteritis, hepatitis, hypophysitis, nephritis, vasculitis, hyperthyroidism, and asthma requiring bronchodilator therapy). Patients with skin disease that doesn't require systemic treatment (e.g., vitiligo, psoriasis, or alopecia) will be allowed to enroll. Has a known history of human immunodeficiency virus (HIV), has hepatitis B surface antigen (HBsAg) positive with hepatitis B virus (HBV) DNA copy number of ≥1000cps/ml or hepatitis C virus (HCV) antibody positive. Has received a live vaccine within 4 weeks of planned start of study treatment. Pregnancy or breast feeding. Cannot complete regular follow-up.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ming-Yuan Chen, MD, PhD
Phone
86-20-8734-3361
Email
chmingy@mail.sysu.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Youping Liu, PhD
Phone
86-13751763276
Email
liuyoup@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
Principal Investigator
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
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ming-Yuan Chen, MD,PhD
Phone
86-20-8734-2422
Email
chmingy@mail.sysu.edu.cn

12. IPD Sharing Statement

Learn more about this trial

Reduced-target Resection After Induction Chemotherapy in Resectable Recurrent Nasopharyngeal Carcinoma

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