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)

NCT06241599 | Recruiting Phase 2 DMC

• 1 other identifier: 2023-FXY-023
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• PFS

  Progression-free survival

  24 months

Study Arms (2)

AK104

EXPERIMENTAL

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

Drug: GP/PFLL+AK104

Placebo

PLACEBO COMPARATOR

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

Drug: GP/PFLL+placebo

Interventions

GP/PFLL+AK104 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).

AK104

GP/PFLL+placebo 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).

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

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

Guangzhou, Guangdong, 510060, China

RECRUITING

MeSH Terms

Conditions

Recurrence; Nasopharyngeal Carcinoma

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: January 28, 2024
• First Posted: February 5, 2024
• Study Start: February 1, 2024
• Primary Completion: February 1, 2026
• Study Completion (Estimated): February 1, 2029
• Last Updated: February 5, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)