A Multi-center, Randomized, Double-blind, Phase II/III Clinical Trial of AK104 or Placebo in Combination With Chemotherapy as Second-line or More Lines for Recurrent or Metastatic Nasopharyngeal Carcinoma (NPC)

NCT ID: NCT06241599

Last Updated: 2024-02-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-02-01
• Study Completion Date: 2029-02-01

Brief Summary

To compare whether AK104 combined with GP or PFLL can improve survival benefit, safety and tolerability in nasopharyngeal carcinoma patients who have failed first-line treatment; To compare the survival benefits of GP or GFLL treatment in nasopharyngeal carcinoma patients who had failed first-line therapy; To compare the survival benefits of GP or GFLL combined with AK104 in patients with nasopharyngeal carcinoma who had failed first-line therapy.

Conditions

Recurrent or Metastatic Nasopharyngeal Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

AK104

AK104: 6mg/kg intravenous infusion for more than 60 minutes

Group Type: EXPERIMENTAL

GP/PFLL+AK104

Intervention Type: DRUG

Groups 1 and 2: Patients who have not been treated with PFLL in front-line therapy. 5-Fu:200mg/m2/d, d1-30, continuous intravenous infusion; Cisplatin: 80mg/m2, intravenous infusion for 4h, the first and 28th days of each cycle; AK104: 6mg/kg intravenous infusion for more than 60 minutes, used on days 1, 15, 30, 45 of each cycle, and administered 30 minutes before chemotherapy drugs during chemotherapy.

Groups 3 and 4: Patients who had never used GP in their front-line treatment regimen. Gemcitabine: 1000mg/m2, used on the 1st and 8th day of each cycle; Cisplatin: 80mg/m2 on the first day of each cycle; AK104 6mg/kg intravenous infusion for more than 60 minutes was used on day 1, 15 (single cycle)/or day 8 (double cycle) of each cycle, and was administered 30 minutes before chemotherapy drugs during chemotherapy. Every 3 weeks is a treatment cycle, with a maximum of 6 cycles used. After 6 cycles of chemotherapy, both groups could continue to receive AK104 (once every 2 weeks).

Placebo

placebo: 6mg/kg intravenous infusion for more than 60 minutes

Group Type: PLACEBO_COMPARATOR

GP/PFLL+placebo

Intervention Type: DRUG

Groups 1 and 2: Patients who have not been treated with PFLL in front-line therapy. 5-Fu:200mg/m2/d, d1-30, continuous intravenous infusion; Cisplatin: 80mg/m2, intravenous infusion for 4h, the first and 28th days of each cycle; placebo: 6mg/kg intravenous infusion for more than 60 minutes, used on days 1, 15, 30, 45 of each cycle, and administered 30 minutes before chemotherapy drugs during chemotherapy.

Groups 3 and 4: Patients who had never used GP in their front-line treatment regimen. Gemcitabine: 1000mg/m2, used on the 1st and 8th day of each cycle; Cisplatin: 80mg/m2 on the first day of each cycle; placebo 6mg/kg intravenous infusion for more than 60 minutes was used on day 1, 15 (single cycle)/or day 8 (double cycle) of each cycle, and was administered 30 minutes before chemotherapy drugs during chemotherapy. Every 3 weeks is a treatment cycle, with a maximum of 6 cycles used. After 6 cycles of chemotherapy, both groups could continue to receive placebo (once every 2 weeks).

Interventions

GP/PFLL+AK104

Groups 1 and 2: Patients who have not been treated with PFLL in front-line therapy. 5-Fu:200mg/m2/d, d1-30, continuous intravenous infusion; Cisplatin: 80mg/m2, intravenous infusion for 4h, the first and 28th days of each cycle; AK104: 6mg/kg intravenous infusion for more than 60 minutes, used on days 1, 15, 30, 45 of each cycle, and administered 30 minutes before chemotherapy drugs during chemotherapy.

Groups 3 and 4: Patients who had never used GP in their front-line treatment regimen. Gemcitabine: 1000mg/m2, used on the 1st and 8th day of each cycle; Cisplatin: 80mg/m2 on the first day of each cycle; AK104 6mg/kg intravenous infusion for more than 60 minutes was used on day 1, 15 (single cycle)/or day 8 (double cycle) of each cycle, and was administered 30 minutes before chemotherapy drugs during chemotherapy. Every 3 weeks is a treatment cycle, with a maximum of 6 cycles used. After 6 cycles of chemotherapy, both groups could continue to receive AK104 (once every 2 weeks).

Intervention Type: DRUG

GP/PFLL+placebo

Groups 1 and 2: Patients who have not been treated with PFLL in front-line therapy. 5-Fu:200mg/m2/d, d1-30, continuous intravenous infusion; Cisplatin: 80mg/m2, intravenous infusion for 4h, the first and 28th days of each cycle; placebo: 6mg/kg intravenous infusion for more than 60 minutes, used on days 1, 15, 30, 45 of each cycle, and administered 30 minutes before chemotherapy drugs during chemotherapy.

Groups 3 and 4: Patients who had never used GP in their front-line treatment regimen. Gemcitabine: 1000mg/m2, used on the 1st and 8th day of each cycle; Cisplatin: 80mg/m2 on the first day of each cycle; placebo 6mg/kg intravenous infusion for more than 60 minutes was used on day 1, 15 (single cycle)/or day 8 (double cycle) of each cycle, and was administered 30 minutes before chemotherapy drugs during chemotherapy. Every 3 weeks is a treatment cycle, with a maximum of 6 cycles used. After 6 cycles of chemotherapy, both groups could continue to receive placebo (once every 2 weeks).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age ≥18 years and ≤75 years; 2. Non-keratinized differentiated or undifferentiated nasopharyngeal carcinoma confirmed by pathology; 3. For patients with recurrent and metastatic nasopharyngeal carcinoma who are not eligible for local treatment and meet the definition of the staging system (8th edition) of the International Union against Cancer and the American Joint Committee on Cancer (UICC/AJCC), local treatment mainly refers to measures related to anti-tumor treatment, including surgery, radiofrequency ablation, transhepatic arterial chemoembolization (TACE), radiotherapy (except for patients with bone metastasis). A locally appropriate dose of radiotherapeutic therapy for symptomatic relief) 4. Patients with nasopharyngeal carcinoma recurrence and metastasis who failed first-line treatment; 5.ECOG performance score 0 or 1; 6. There is at least one measurable lesion according to the RECIST1.1 evaluation criteria, and a lesion that has previously received, for example, radiation therapy can be considered a target lesion if there is objective evidence of disease progression. 7. Patients are required to provide tissue samples within three years prior to enrollment; 8. Expected survival ≥3 months; 9. The functions of vital organs meet the following requirements (no blood components, cell growth factors, whitening drugs, thrombocytophytics, or anemia correction drugs are allowed within 14 days before screening) : · Neutrophil absolute count (ANC) ≥1.5×109/L· Platelets ≥100×109/L; · Hemoglobin ≥8.0g/dl (note: Hemoglobin ≥8.0g/dl through blood transfusion or other intervention is acceptable); · Serum albumin ≥2.8g/dL; · Bilirubin ≤ 1.5x ULN, ALT and AST≤ 1.5x ULN; If there is liver metastasis, ALT and AST are less than 5 times ULN. Creatinine clearance ≥50mL/min (using the standard CockcroftGault formula, see Annex II); 10. Women of reproductive age who have an unsterilized sexual partner should use at least one highly effective form of birth control; 11. Unsterilized men with a partner of childbearing age must use a highly effective form of birth control from day 1 to day 120 of the last use of the study drug; 12. Informed consent has been signed.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Yun-fei Xia

Prof.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Department of Radiation Oncology, Sun Yat-Sen University Cancer Center

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Facility Contacts

Yun-fei Xia, MD

Role: primary

xiayf@sysucc.org.cn

+8613602805461

Zilu Huang, MD

Role: backup

huangzl1@sysucc.org.cn

+15605332112

Other Identifiers

2023-FXY-023

Identifier Type: -

Identifier Source: org_study_id