Trial Title:
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
Condition:
Recurrent or Metastatic Nasopharyngeal Carcinoma
Conditions: Official terms:
Carcinoma
Nasopharyngeal Carcinoma
Recurrence
Study type:
Interventional
Study phase:
Phase 2/Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
Triple (Participant, Care Provider, Investigator)
Intervention:
Intervention type:
Drug
Intervention name:
GP/PFLL+AK104
Description:
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).
Arm group label:
AK104
Intervention type:
Drug
Intervention name:
GP/PFLL+placebo
Description:
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).
Arm group label:
Placebo
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.
Criteria for 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.
Exclusion Criteria:
1. Previous history of allergy to 5-Fu, cisplatin, gemcitabine, other monoclonal
antibodies or any component of CTLA-4 and PD1 bispecial antibodies; In the past,
CTLA-4 and PD1-specific antibody therapy were used simultaneously. 2. 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; 3.
The subject has any active autoimmune disease or a history of autoimmune disease
(e.g., but not limited to: interstitial pneumonia, uveitis, enteritis, hepatitis,
hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism; Subjects with
vitiligo or asthma that has been in complete remission in childhood can be adults
without any intervention.Patients with asthma requiring medical intervention with
bronchodilators were not included); 4. Subjects were taking immunosuppressants, or
systemic, or absorbable local hormone therapy for immunosuppressive purposes (doses
>10mg/ day of prednisone or other therapeutic hormones) and continued to use within
2 weeks prior to enrollment; 5. Known subject is previously allergic to
macromolecular protein preparation ingredients; 6. The subject has clinically
symptomatic central nervous system metastases (e.g. brain edema, need for hormonal
intervention, or progression of brain metastases); Other aggressive malignancies
within 7.5 years, except locally curable (appearing to cure) malignancies such as
basal or squamous cell carcinoma of the skin, superficial cancers of the bladder,
cervix and breast in situ; 8. Active autoimmune disease requiring systemic treatment
within the last two years, except vitiligo, alopecia, Grave disease, psoriasis or
eczema that did not require systemic treatment within the last two years,
hypothyroidism requiring stable hormone replacement therapy only (due to autoimmune
thyroiditis), type 1 diabetes requiring stable dose insulin replacement therapy
only; Childhood asthma that has been completely cured in adulthood without
intervention or primary disease that does not recur unless stimulated by external
factors; 9. Active or previous inflammatory bowel disease (such as Crohn's disease,
ulcerative colitis, or chronic diarrhea); 10. Systemic glucocorticoid therapy (dose
equivalent to 10mg/ day of prednisone) or other immunosuppressants are required
within the first seven days of initial administration of the investigational drug.
11. Having allogeneic organ transplantation or allogeneic hematopoietic stem cell
transplantation; 12. Gastrointestinal perforation or fistula within the first six
months of enrollment; 13. There were necrotic foci within the first four weeks of
enrollment that researchers thought might be a potential source of major
bleeding;14. History of interstitial pneumonia; 15. History of active tuberculosis;
16. Serious infections, including but not limited to complications requiring
hospitalization, sepsis, or severe pneumonia, occur within four weeks prior to the
first application of the investigational drug; 17. Active infections that require
systematic treatment; 18. Untreated chronic hepatitis B or chronic HBVDNA≥1000IU/ml
or active hepatitis C. Non-active HBsAg carriers, stable hepatitis B after treatment
(HBVDNA < 1000IU/ml) and cured hepatitis C can be included. Patients who are
positive for HCV antibodies can only be enrolled if they test negative for HCVRNA.
19. History of major surgery within 30 days before the first application of the
investigational drug; 20. There is meningeal metastasis or active brain metastasis;
21. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring
repeated drainage; 22. Toxicity problems unresolved at the time of previous
antitumor therapy, defined as unresolved to level 0 or 1 of NCICTCAEv5.0, or levels
specified in the inclusion/exclusion criteria, except hair loss. 23. Live attenuated
vaccines were administered within 30 days prior to the first application of the
investigational drug, or live attenuated vaccines were planned to be administered
during the study period. 24. Known history of severe allergy to other monoclonal
antibodies; 25. Pregnant or lactating women; 26. Have clinical symptoms or diseases
of heart that are not well controlled, such as: ① heart failure of NYHA2 or above; ②
Unstable angina pectoris; ③ Myocardial infarction occurred within 1 year; Patients
with clinically significant supraventricular or ventricular arrhythmias requiring
treatment or intervention; 27. Subjects had an active infection or unexplained fever
>38.5 degrees during screening or prior to initial dosing (as determined by the
investigator, subjectsFever due to tumor can be included in the group); •28.
Allergic to AK104 ingredients; 29. The subject has a known history of psychotropic
substance abuse, alcohol abuse, or drug use; 30. According to the investigator's
judgment, the subjects have other factors that may lead to the forced termination of
the study, such as other serious illnesses (including mental illness) requiring
combined treatment, serious abnormalities in laboratory tests, and family or social
factors that may affect the safety of the subjects, or the collection of test data
and samples.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Department of Radiation Oncology, Sun Yat-Sen University Cancer Center
Address:
City:
Guangzhou
Zip:
510060
Country:
China
Status:
Recruiting
Contact:
Last name:
Yun-fei Xia, MD
Phone:
+8613602805461
Email:
xiayf@sysucc.org.cn
Contact backup:
Last name:
Zilu Huang, MD
Phone:
+15605332112
Email:
huangzl1@sysucc.org.cn
Start date:
February 1, 2024
Completion date:
February 1, 2029
Lead sponsor:
Agency:
Sun Yat-sen University
Agency class:
Other
Source:
Sun Yat-sen University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06241599
