PFLL Combined With PD-1 Antibody With or Without FMT for Oligometastatic NPC,a Phase III ,Open, Randomized Clinical Trial.

There is a correlation between gut microbiota and immunotherapy reactivity, and regulating gut microbiota through FMT can prevent primary resistance to immune checkpoint inhibitors and further improve the effectiveness of tumor immunotherapy.Therefore, on the basis of previous studies, this study intends to explore whether intestinal flora transplantation can improve the anti-tumor efficacy of low-dose long term 5-FU pumping ("old fire soup") therapy combined with immunotherapy and reduce the occurrence of toxic side effects in patients with metastatic nasopharyngeal carcinoma.

Study Overview

• Status: Not yet recruiting
• Conditions: Nasopharyngeal Carcinoma
• Intervention / Treatment: Drug: Intestinal bacteria freeze-dried powder capsules

Detailed Description

Experimental group (PFLL + PD-1 + FMT) :

5-Fu 200mg/ m2 /d, D1-30 + cisplatin 80mg/ m2, d1, 28 or D1-3, 28-30 + triplizumab 240mg, d1, 22 + FMT 10 capsules in the morning, middle and evening, D-5-3, 11-13, 38-40;Every 60 days/cycle, PFLL + PD-1 + FMT is given for a maximum of 6 cycles.

Control group (PFLL + PD-1) :

5-Fu 200mg/ m2 /d, D1-30 + cisplatin 80mg/ m2, d1, 28 or D1-3, 28-30 + triplizumab 240mg, d1, 22;PFLL + PD-1 is given a maximum of 6 cycles per 60 days/cycle.

• Study Type: Interventional
• Enrollment (Estimated): 96
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 18-60 years old;
2. Pathological diagnosis of nasopharyngeal carcinoma;
3. Patients diagnosed with oligometastatic nasopharyngeal carcinoma who meet stage IVb as defined by the International Union against Cancer and the American Joint Committee on Cancer (UICC/AJCC) staging System (8th edition) (Oligometastatic as ≤3 organs and ≤5 sites of metastasis);
4. Patients with metastatic nasopharyngeal carcinoma who had not previously received systematic chemotherapy for the disease in this study, except neoadjuvant chemotherapy, concurrent chemoradiotherapy or adjuvant chemotherapy received 6 months before the first administration;
5. Karnofsky's functional status score should be at least 70 points (if the functional status score is decreased due to tumor, it should be appropriately relaxed after the researchers' judgment, and the minimum score should be no less than 50 points, as shown in Annex I);
6. According to the RECIST1.1 evaluation criteria, there should be at least 1 measurable lesion, and the measurable lesion should not have received local treatment such as radiotherapy;
7. Expected survival ≥3 months;
8. A tolenrant organs.

Exclusion Criteria:

1. allergy to 5-FU, gemcitabine, cisplatin, other monoclonal antibodies, or any component of triplimab
2. Prior treatment with PD-1 receptor or its ligand PD-L1 or cytotoxic T lymphocyte-associated protein 4 (CTLA4) receptor;
3. Had major surgery other than diagnosis of nasopharyngeal cancer within 28 days prior to randomization or was expected to require major surgery during the study period;
4. Patients with severe damage of intestinal barrier such as sepsis, active massive bleeding of digestive tract and perforation due to various reasons;
5. Currently diagnosed with fulminant colitis or toxic megacolon;
6. Enteral nutrition patients who cannot tolerate 50% of heat calorie requirements due to severe diarrhea, significant fibrous intestinal stenosis, severe gastrointestinal bleeding, high-flow intestinal fistula, etc.;
7. patients with any active autoimmune disease or a history of autoimmune diseases.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Flora Transplantation group; 5-Fu+DDP+anti-PD-1 mAb+FMT	Drug: Intestinal bacteria freeze-dried powder capsules; Oral healthy intestinal bacteria freeze-dried powder capsules, tid; Other Names: 5-FU+DDP+anti-PD-1 mAb
No Intervention: Control group; 5-Fu+DDP+anti-PD-1 mAb

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	Progression-free survival	1-year PFS 40%

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	overall survival	24 months

Collaborators and Investigators

• Sponsor: Yun-fei Xia

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2024
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: June 21, 2024
• First Submitted That Met QC Criteria: June 26, 2024
• First Posted (Actual): July 3, 2024

Study Record Updates

• Last Update Posted (Actual): July 3, 2024
• Last Update Submitted That Met QC Criteria: June 26, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Nasopharyngeal Neoplasms; Nasopharyngeal Carcinoma
• Other Study ID Numbers: 2023-FXY-120

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No