Trial Title:
Anti-PD1 Monoclonal Antibody Combined With Nimotuzumab and Capecitabine in Patients With First-line Platinum-resistant Recurrent/Metastatic Nasopharyngeal Carcinoma
NCT ID:
NCT06259721
Condition:
Nasopharyngeal Carcinoma
Conditions: Official terms:
Carcinoma
Nasopharyngeal Carcinoma
Capecitabine
Nimotuzumab
Antibodies
Conditions: Keywords:
Nasopharyngeal Carcinoma
anti-PD1 antibody
Nimotuzumab
Capecitabine
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Anti-PD1 antibody, nimotuzumab and capecitabine
Description:
Combination phase Anti-PD1 monoclonal antibody: Choose one of the anti-PD-1 monoclonal
antibody drugs reimbursed by medical insurance, toripalimab (240mg), camrelizumab
(200mg), tislelizumab (200mg) or others; Intravenous infusion, every 3 weeks .
Nimotuzumab:: In the first 6 cycles, 200 mg, intravenous infusion, every 1 week, and 400
mg is administered for the first time.
Capecitabine: 1000 mg/m2, orally twice daily on days 1-14, every 3 weeks
Maintenance phase:
Anti-PD1 monoclonal antibody: anti-PD-1 monoclonal antibody drugs, Intravenous infusion,
every 3 weeks.
Nimotuzumab treatment: 400 mg, intravenous infusion, every 3 weeks. Capecitabine: 1000
mg/m2, orally twice daily on days 1-14, every 3 weeks；
The duration of treatment is 1 year or until intolerable toxic reactions occur, or
disease progresses, or the patient withdraws consent, or the investigator determines that
the patient needs to withdraw from treatment.
Arm group label:
Combination Treatment
Summary:
The purpose of this study is to explore the efficacy and safety of a combination regimen
of Anti-PD1 monoclonal antibody, nimotuzumab, and capecitabin in treating recurrent or
metastatic nasopharyngeal carcinoma patients who have failed first-line platinum-based
chemotherapy.
Detailed description:
Currently, there is still no uniform treatment regimen for treating recurrent or
metastatic nasopharyngeal carcinoma patients who failed to first-line platinum-based
chemotherapy. Anti-PD-1 monoclonal antibody showed efficacy and safety in previous
studies, however, the efficacy of immunotherapy alone was limited. Immunotherapy combined
with other treatment regimens for recurrent or metastatic nasopharyngeal carcinoma is a
strategy that needs to be urgently explored. Epidermal growth factor receptor (EGFR) is
an important target in the treatment of nasopharyngeal carcinoma. Nimotuzumab, an EGRF
antibody selectively inhibits epidermal growth factor receptors, has shown strong
clinical utility in Nasopharyngeal Carcinoma. Nimotuzumab is an IgG1 monoclonal antibody
targeting EGFR. It can not only effectively block the EGFR signaling pathway to promote
cell death, but also activate immunity through ADCC to mediate anti-tumor effects.
Anti-PD-1 antibodies relieve inhibition of cytotoxic lymphocytes to promote tumor
regression. Nimotuzumab targeting EGFR mediates antibody-dependent cellular cytotoxicity
and promotes communication between immune cells, including natural killer and dendritic
cells. This communication can trigger tumor antigen-specific cellular immunity and
generate antigen-specific T lymphocyte responses. Furthermore, therefore, recruitment of
adaptive and innate immunity and antibody-dependent cellular cytotoxicity may induce
antitumor synergy. Considering that anti-PD1 monoclonal antibodies and nimotuzumab play a
synergistic role in enhancing anti-tumor immunity. The combination of anti-EGFR
monoclonal antibody and anti-PD-1 monoclonal antibody has shown good efficacy in
recurrent and metastatic head and neck squamous cell carcinoma. The overall response rate
(ORR) of the combination treatment reached 45%, better than the ORR of the anti-PD-1
monoclonal antibody alone (20%).
As a new type of fluorouracil oral anticancer drug, capecitabine has better efficacy and
lower toxicity than 5-Fu [14]. Two recent clinical trials have confirmed that maintenance
therapy with capecitabine oral chemotherapy can effectively reduce the risk of metastasis
in locally advanced nasopharyngeal carcinoma, suggesting that new fluorouracil drugs have
good anti-cancer effects. Clinical studies from recurrent metastatic nasopharyngeal
carcinoma also confirmed that capecitabine metronomic therapy can improve overall
survival. Maintenance chemotherapy is a strategy of administering cytotoxic drugs at high
frequency, low doses, and minimal downtime.
Based on this, this study aims to evaluate the efficacy and safety of anti-PD1 monoclonal
antibody combined with nimotuzumab and capecitabine in patients with recurrent or
metastatic nasopharyngeal carcinoma who failed to first-line platinum-based chemotherapy,
to provide new evidence for individualized comprehensive treatment in nasopharyngeal
carcinoma.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Histologically or cytologically confirmed with recurrent or metastatic
nasopharyngeal carcinoma which is not amenable to curative treatment with surgery
and/or radiation therapy. If the patient refuses biopsy of metastatic lesions, those
diagnosed with metastasis based on imaging evidence and clinical evidence can be
enrolled.
2. Have failed for first-line platinum-based chemotherapy. Previously received
first-line platinum-based chemotherapy for recurrent or metastatic disease and had
disease progression during or after treatment; or recurrence and metastases within 6
months after treatment of platinum-based chemoradiation.
3. Age ≥ 18 years and ≤ 75 years, both genders.
4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
5. The life expectancy of at least 3 months.
6. Patients must have at least 1 lesion that is measurable using RECIST v1.1 criteria.
7. Patients must have adequate organ function (without blood transfusion, without
growth factor or blood components support within 14 days before enrollment) as
determined by:
Absolute neutrophil count (ANC) ≥1.5×109/L; Platelet count ≥ 75×109/L; Hemoglobin ≥
9 g/dL; serum total bilirubin (TBIL) ≤1.5 times the upper limit of normal (ULN);
alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×upper limit
of normal (ULN), (for subjects with liver metastases, TBIL ≤3×ULN; ALT and
AST≤5×ULN); Creatinine ≤1.5×ULN or creatinine clearance rate≥50 ml/min
(Cockcroft-Gault formula); serum albumin ≥28 g/L; Thyroid-stimulating hormone (TSH)
levels ≤1×ULN (however, patients with free Triiodothyronine [FT3] or free Thyroxine
[FT4] levels ≤1× ULN may be enrolled); INR, APTT≤1.5 x ULN.
8. All women with fertility potential must undergo a urine or serum pregnancy test
during screening and the results are negative.
9. Written informed consent.
Exclusion Criteria:
-
1. Those with a history of severe immediate allergy to any drugs used in this
study; 2. Patients who have previously received anti-EGFR monoclonal antibodies
(nitolizumab, cetuximab) and anti-PD-1 monoclonal antibodies.
3. Combined with other malignant tumors; 4. Any of the following conditions exist
within 6 months before screening: myocardial infarction, severe/unstable
angina, coronary artery/peripheral artery bypass grafting, symptomatic
congestive heart failure, cerebrovascular accident, transient cerebral ischemia
Paroxysmal or symptomatic pulmonary embolism. Patients with known coronary
artery disease, congestive heart failure that does not meet the above criteria,
or left ventricular ejection fraction <50% must be treated with an optimized
and stable medical regimen as determined by the treating physician, who may
consult a cardiologist if appropriate; 5. Patients who have received any of the
following treatments:
(1) Have received any investigational drugs within 4 weeks before using the
investigational drugs for the first time; (2) Use of large amounts of
glucocorticoids or other immunosuppressants (including but not limited to
prednisone, dexamethasone, azathioprine, methotrexate, thalidomide and anti-tumor
necrosis factor within 4 weeks before treatment (drugs against TNF), or subjects who
require hormonal therapy during clinical trials. Other special circumstances need to
be communicated with the sponsor. In the absence of active autoimmune disease,
inhaled or topical steroids and adrenocortical hormone replacement at doses >10
mg/day prednisone therapeutic dose are allowed; (4) Those who have received
anti-tumor vaccines or have received live vaccines within 4 weeks before the first
administration of the study drug; (5) Have undergone major surgery or serious trauma
within 4 weeks before using the study drug for the first time; (6) Enroll in another
clinical study at the same time, unless it is an observational (non-interventional)
clinical study or an interventional clinical study follow-up; 6. Patients with
active autoimmune diseases or a history of autoimmune diseases that may relapse
Note: Patients with the following diseases are not excluded and can enter further
screening:
1. Controlled type 1 diabetes
2. Hypothyroidism (if it can be controlled with hormone replacement therapy alone)
3. Skin diseases that do not require systemic treatment (such as vitiligo, psoriasis,
alopecia)
4. Any other disease that is not expected to recur in the absence of external triggers
7. Active infections, including tuberculosis, hepatitis B, hepatitis C and human
immunodeficiency virus. Patients with positive HBV surface antigen (HBsAg) but HBV
DNA <1000 copies/mL are eligible to participate in this study; patients with
positive HCV antibody test results can only participate if the HCV RNA polymerase
chain reaction test result is negative. Selected for this study; 8. History of
idiopathic pulmonary fibrosis, drug-induced pneumonia, organizing pneumonia
(bronchiolitis obliterans), idiopathic pneumonia or evidence of active pneumonia on
chest CT scan during screening; 9. No capacity for civil conduct or limited capacity
for civil conduct; 10. Drug abuse or alcohol addiction, the patient has physical or
mental illness, and the researcher believes that the patient cannot fully or fully
understand the possible complications of this study; 11. Other serious acute or
chronic medical conditions that may increase the risks related to the treatment of
the research protocol, or may interfere with the interpretation of the research
results and (according to the investigator's judgment) may make the patient unfit to
participate in this study (including immune colitis, inflammatory colitis,
Enteropathy, non-infectious pneumonia, pulmonary fibrosis) or mental illness
(including dementia and epilepsy, suicidal ideation or behavior recently, within the
past year, or active) or abnormal laboratory tests; 12. Previously diagnosed with
immunodeficiency or known diseases related to human immunodeficiency virus (HIV) or
acquired immunodeficiency syndrome (AIDS); 13. Pregnant or lactating female
patients, male or female patients with childbearing potential but unwilling or
unable to use contraception during the entire study period and for at least 1 year
after the end of the treatment plan; 14. Those with recurrent nasopharyngeal
carcinoma are suitable for surgical treatment.
Gender:
All
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Department of Nasopharyngeal Carcinoma, Jiangxi Cancer Hospital
Address:
City:
Nanchang
Zip:
330029
Country:
China
Status:
Recruiting
Contact:
Last name:
Tianzhu Lu
Phone:
8615270186250
Email:
lutianzhu2008@163.com
Investigator:
Last name:
Jingao Li, PhD
Email:
Principal Investigator
Investigator:
Last name:
Xiaochang Gong, PhD
Email:
Sub-Investigator
Start date:
February 10, 2024
Completion date:
August 9, 2026
Lead sponsor:
Agency:
Jiangxi Provincial Cancer Hospital
Agency class:
Other
Source:
Jiangxi Provincial Cancer Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06259721
