A Single-arm, Multicenter, Phase Ib/II Clinical Study of Docetaxel for Injection (Albumin-bound) in Combination With Nivolumab in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN) Progressing on or After Platinum-based Therapy
Overview
- Phase
- Phase 1
- Intervention
- Docetaxel
- Conditions
- Squamous Cell Carcinoma of Head and Neck
- Sponsor
- CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
- Enrollment
- 94
- Locations
- 1
- Primary Endpoint
- Phase II: Objective response rate (ORR)
- Last Updated
- 3 years ago
Overview
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.
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/m\^2 and 100 mg/m\^2) 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
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age ≥ 18 years old and voluntarily signed the informed consent form.
- •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.
- •Patients with platinum-based regimen failure, defined as:
- •. Recurrent or metastatic SCCHN with disease progression during or after platinum-based therapy;
- •. Locally advanced head and neck carcinoma with recurrence or metastasis within 6 months after platinum-based therapy in previous multimodal therapy.
- •Previous or qualified tumor tissue samples are available for testing PD-L
- •Patients with oropharyngeal carcinoma should provide previous HPVp16 immunohistochemical test results, or eligible tumor tissue samples for testing HPV status.
- •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).
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0-
- •Life expectancy ≥ 3 months.
Exclusion Criteria
- •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).
- •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.
- •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.
- •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.
- •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.
- •Patients with a history of severe cardiovascular disease within 6 months before the first dose of the investigational drug, including but not limited to:
- •. Severe heart rhythm or conduction abnormalities, such as ventricular arrhythmia requiring clinical intervention and third-degree atrioventricular block;
- •. History of myocardial infarction, angina pectoris, angioplasty and coronary artery bypass surgery;
- •. Heart failure with New York Heart Association (NYHA) Classification of Class III and above;
- •. Poorly controlled hypertension.
Arms & Interventions
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.
Intervention: Docetaxel
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.
Intervention: Nivolumab
Outcomes
Primary Outcomes
Phase II: Objective response rate (ORR)
Time Frame: 2 years
Objective response rate
Phase Ib: Incidence of adverse events and serious adverse events
Time Frame: 6 weeks
Incidence of adverse events and serious adverse events
Secondary Outcomes
- The pharmacokinetic parameters (free docetaxel and total docetaxel) : t½(24 hours)
- The pharmacokinetic parameters (free docetaxel and total docetaxel) : AUC0-∞(24 hours)
- Phase II: Disease control rate (DCR)(2 years)
- The pharmacokinetic parameters (free docetaxel and total docetaxel) : Cmax(24 hours)
- The pharmacokinetic parameters (free docetaxel and total docetaxel) : Tmax(24 hours)
- The pharmacokinetic parameters (free docetaxel and total docetaxel) : Vd(24 hours)
- Phase II: Duration of response (DOR)(2 years)
- Phase II: Overall survival (OS)(2 years)
- Phase II: Incidence of adverse events and serious adverse events(2 years)
- The pharmacokinetic parameters (free docetaxel and total docetaxel) : AUC0-last(24 hours)
- The pharmacokinetic parameters (free docetaxel and total docetaxel) : CL(24 hours)
- Phase II: Progression-free survival (PFS)(2 years)