A Study of Docetaxel for Injection (Albumin-bound) in Combination With Nivolumab in Patients With Head and Neck (SCCHN)
Study Details
Study Description
Brief Summary
This trial is a single-arm, multicenter phase Ib/II clinical study to evaluate the efficacy and safety of Docetaxel for Injection (Albumin-bound) combined with Nivolumab and the pharmacokinetic characteristics of Docetaxel in patients with recurrent or metastatic SCCHN who are positive for PD-L1 expression and have progressed on or after platinum-based therapy.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1/Phase 2 |
Detailed Description
This study will be conducted in two stages (phase Ib and phase II). Phase Ib: To explore the safety and tolerability of Docetaxel for Injection (Albumin-bound) (75 mg/m2 and 100 mg/m2) combined with Nivolumab 360 mg. Dose exploration will be started at low dose and proceed in turn.
Phase II: According to the recommended phase II dose (RP2D) determined in the phase Ib study, a phase II study of Docetaxel for Injection (Albumin-bound) combined with Nivolumab will be conducted to observe the efficacy of the combination regimen, with ORR as the primary study endpoint. Simon's optimal 2-stage design will be adopted for phase II study.
All patients in Phase Ib and Phase II will be treated with Docetaxel for Injection (Albumin-bound) combined with Nivolumab until participants meet the criteria for termination or withdrawal criteria, for a maximum of 2 years
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Docetaxel combined with Nivolumab Phase Ib: The eligible patients with SCCHN will received Docetaxel for Injection (Albumin-bound) 75 mg/m^2 or 100 mg/m^2 sequentially in combination with Nivolumab 360 mg to evaluate safety and efficacy and explore RP2D. Phase II: According to the RP2D determined in the phase Ib study, patients will be treated with Docetaxel for Injection (Albumin-bound) combined with Nivolumab until participants meet the criteria for termination or withdrawal criteria, for a maximum of 2 years. |
Drug: Docetaxel
Docetaxel for Injection (Albumin-bound), Q3W, i.v. 60 min
Drug: Nivolumab
Nivolumab, Q3W, i.v. 30 min
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Outcome Measures
Primary Outcome Measures
- Phase Ib: Incidence of adverse events and serious adverse events [6 weeks]
Incidence of adverse events and serious adverse events
- Phase II: Objective response rate (ORR) [2 years]
Objective response rate
Secondary Outcome Measures
- The pharmacokinetic parameters (free docetaxel and total docetaxel) : AUC0-last [24 hours]
Area under the plasma concentration versus time curve (AUC)
- The pharmacokinetic parameters (free docetaxel and total docetaxel) : AUC0-∞ [24 hours]
Area under the plasma concentration versus time curve (AUC)
- The pharmacokinetic parameters (free docetaxel and total docetaxel) : Cmax [24 hours]
The Cmax is the maximum observed serum concentration of Docetaxel
- The pharmacokinetic parameters (free docetaxel and total docetaxel) : Tmax [24 hours]
The Tmax is the time at which the maximum concentration of Docetaxel
- The pharmacokinetic parameters (free docetaxel and total docetaxel) : t½ [24 hours]
Terminal elimination half-life (t1/2) of docetaxel
- The pharmacokinetic parameters (free docetaxel and total docetaxel) : Vd [24 hours]
Volume of distribtion of docetaxel
- The pharmacokinetic parameters (free docetaxel and total docetaxel) : CL [24 hours]
Clearance of Docetaxel
- Phase II: Disease control rate (DCR) [2 years]
Disease control rate
- Phase II: Duration of response (DOR) [2 years]
Duration of response
- Phase II: Progression-free survival (PFS) [2 years]
Progression-free survival
- Phase II: Overall survival (OS) [2 years]
Overall survival
- Phase II: Incidence of adverse events and serious adverse events [2 years]
Incidence of adverse events and serious adverse events
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age ≥ 18 years old and voluntarily signed the informed consent form.
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Patients with histologically or cytologically confirmed SCCHN (primary tumor located in the oral cavity, oropharynx, larynx or hypopharynx), with positive PD-L1 expression, and who are not suitable for local radical therapy.
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Patients with platinum-based regimen failure, defined as:
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. Recurrent or metastatic SCCHN with disease progression during or after platinum-based therapy;
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. Locally advanced head and neck carcinoma with recurrence or metastasis within 6 months after platinum-based therapy in previous multimodal therapy.
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Previous or qualified tumor tissue samples are available for testing PD-L1.
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Patients with oropharyngeal carcinoma should provide previous HPVp16 immunohistochemical test results, or eligible tumor tissue samples for testing HPV status.
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At least one measurable lesion confirmed by CT or MRI according to RECISTv1.1 (previously irradiated, progressive disease or tumor persistence ≥ 3 months after radiotherapy can be considered as measurable lesions).
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Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.
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Life expectancy ≥ 3 months.
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Main organ function meets the following criteria within 7 days before treatment (no medical supportive treatments such as blood component transfusion, human granulocyte colony-stimulating factor (G-CSF), thrombopoietin (TPO), interleukin-11, and erythropoietin (EPO) within 2 weeks before administration of the investigational product).
Absolute neutrophil count ≥1.5×109/L Platelets ≥90×109/L Hb≥90 g/L or ≥5.6 mmol/L Serum creatinine ≤ 1.5×ULN or creatinine clearance rate ≥ 40 mL/min Total bilirubin ≤1.0×ULN (≤ 1.5 × ULN for patients with liver metastasis or liver cancer); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5 × ULN ( ≤ 2.5 × ULN for patients with liver metastasis or liver cancer); Activated Partial Thromboplastin Time (APTT) ≤ 1.5×ULN, International Normalized Ratio (INR) ≤ 1.5×ULN.
- Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days prior to the first dose of the investigational drug. The patient and his/her spouse must agree to take adequate contraception from signing of ICF through 6 months after last dose, during which time women should be nonlactating and men should refrain from donating sperm.
Exclusion Criteria:
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Histologically or cytologically confirmed recurrent or metastatic nasopharyngeal carcinoma, SCCHN with unknown primary lesion, salivary gland carcinoma, or non-squamous tissue carcinoma (e.g., mucosal melanoma).
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Patients with active brain metastasis and leptomeningeal metastasis. Patients with brain metastasis for whom there is no evidence of PD by MRI at least 8 weeks after treatment and within 28 days before the first dose of the investigational drug can be included; Those who do not require systemic cortisol therapy (prednisone > 10 mg/day or equivalent) at least 2 weeks before the first dose of the investigational drug can be included; Patients with skull base lesions without definite evidence of dural or parenchymal brain involvement can be considered to be included only after discussion with the sponsor's medical monitor.
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History of other malignancies within 5 years prior to the first dose of the investigational drug, except for the following: a. Any other invasive malignancy (for which the patient has received adequate treatment) with disease free status lasting > 3 years, which will not affect the assessment of tumor efficacy as assessed by the investigator; b. Cured basal cell or squamous cell skin carcinoma, superficial bladder cancer, prostate cancer, cervical cancer, or breast cancer in situ, and other locally curable cancers.
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Patients with known or suspected autoimmune disease within 2 years before the first dose of the investigational drug, except for the following: a. well-controlled type I diabetes; b. well-controlled hypothyroidism requiring only hormone replacement therapy; c. skin diseases (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment; d. patients who are not expected to relapse in the absence of external triggers.
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Patients with an uncontrollable third space effusion (e.g. pleural effusion, ascites, or pericardial effusion), who, in the judgment of the investigator, are not suitable for the study.
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Patients with a history of severe cardiovascular disease within 6 months before the first dose of the investigational drug, including but not limited to:
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. Severe heart rhythm or conduction abnormalities, such as ventricular arrhythmia requiring clinical intervention and third-degree atrioventricular block;
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. History of myocardial infarction, angina pectoris, angioplasty and coronary artery bypass surgery;
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. Heart failure with New York Heart Association (NYHA) Classification of Class III and above;
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. Poorly controlled hypertension.
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Patients with prolonged QT/QTc interval (QTcF > 480 ms, Fridericia's formula: QTcF = QT/RR^0.33, RR = 60/heart rate) by ECG during the screening period and/or with left ventricular ejection fraction (LVEF) ≤ 50% by echocardiography (ECHO) or multi-gated acquisition (MUGA) during the screening period;
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Patients with positive HCV antibody (+) (patients with negative HCV RNA can be included, and anti-HCV treatment other than interferon is allowed), active hepatitis B (patients with HBV DNA ≤ 500 IU/mL can be included, and anti-HBV treatment other than interferon is allowed), known HIV positive or known acquired immunodeficiency syndrome (AIDS) during the screening period.
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Patients who have undergone major organ surgery within 4 weeks before the first dose of the investigational drug, or who need to undergo elective surgery during the study.
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Patients who fail to recover from the toxic responses caused by previous anti-tumor treatment to Grade 1 and below (CTCAE 5.0), except for the following: Grade 2 neuropathy, alopecia, hypothyroidism caused by previous anti-tumor treatment (including hormone replacement therapy) and toxicity without safety risks as judged by the investigator.
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Patients who have previously received T cell costimulating drugs or drugs acting on immune checkpoint pathways (including PD-1, PD-L1/2, CTLA-4 inhibitors, etc.).
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Patients who have previously received other immunotherapies and experienced ≥ Grade 3 irAE (immune-related adverse event).
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Patients who have previously received taxanes (patients who previously received taxane-containing induction chemotherapy and progressed after 6 months can be included).
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Patients who have received anti-tumor treatments such as chemotherapy, radiotherapy, targeted therapy, immunotherapy and other clinical study drugs within 4 weeks before the first dose of the investigational drug, and other conditions are as follows:
Local palliative radiotherapy within 2 weeks before the first dose of the investigational drug; oral fluoropyrimidines, small molecule targeted drugs, etc. within 2 weeks before the first dose of the investigational drug or within known 5 half-lives of the drug (whichever is longer); Traditional Chinese medicines with anti-tumor indications within 2 weeks before the first dose of the investigational drug.
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Patients who have received corticosteroid (prednisone > 10 mg/day or equivalent) or other immunosuppressive therapies within 2 weeks before the first dose of the investigational drug, except for the following: a. use of topical, ocular, intra-articular, intranasal and inhaled glucocorticoids; b. short-term use of glucocorticoids for prophylaxis (such as prevention of contrast agent allergy).
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Patients who have received live attenuated vaccine within 2 weeks before the first dose of the investigational drug or planned to receive live attenuated vaccine during the study period.
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Patients who have used potent inhibitors or inducers of CYP3A4 within 2 weeks before the first dose of the investigational drug.
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Patients with known ≥ Grade 3 hypersensitivity and/or contraindication to albumin or monoclonal antibodies.
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Other situations that the investigator considers not suitable for participating in the clinical study, including but not limited to: the patient is complicated by severe or uncontrolled medical conditions, which interfere with the interpretation of study results and affect the study compliance.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Guo Ye | Shanghai | Shanghai | China | 200031 |
Sponsors and Collaborators
- CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- HB1801-CSP-003