NCT03422536已完成2 期
A Randomized, Phase II Study of Ficlatuzumab With or Without Cetuximab in Patients With Cetuximab-Resistant, Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 78
- 试验地点
- 6
- 主要终点
- Progression Free Survival (PFS)
研究概览
简要总结
This randomized phase II trial studies how well ficlatuzumab with or without cetuximab works in treating patients with head and neck squamous cell carcinoma that has come back or spread to other places in the body and resistant to cetuximab treatment. Monoclonal antibodies, such as ficlatuzumab and cetuximab, may block growth signals that lets a tumor cell survive and reproduce, and helps the immune system recognize and fight head and neck squamous cell carcinoma.
详细描述
PRIMARY OBJECTIVES:
I. To assess the efficacy of ficlatuzumab, with or without concurrent cetuximab, in patients with cetuximab-resistant, recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) as measured by progression-free survival (PFS).
SECONDARY OBJECTIVES:
I. To describe toxicity. II. To evaluate response rate and overall survival in both treatment arms.
EXPLORATORY OBJECTIVES I. To describe patient reported quality of life
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have histologically confirmed HNSCC from any primary site, except nasopharyngeal if World Health Organization (WHO) Type III (non-keratinizing and Epstein-Barr virus (EBV)-positive)).
- •Eligible histologies include:
- •Basaloid, poorly differentiated, and undifferentiated carcinoma histologies.
- •Nasopharyngeal carcinoma, WHO Type I and II (keratinizing, non-EBV positive).
- •Paranasal sinus, lip and external auditory canal sites.
- •Squamous cell carcinoma of unknown primary, clearly related to the head and neck.
- •Note: Documentation of primary site diagnosis must be submitted with the registration request.
- •Patients must have recurrent and/or metastatic disease, fulfilling at least one of the criteria defined below:
- •Incurable disease as assessed by surgical or radiation oncology;
- •Metastatic (M1) disease;
- •Persistent or progressive disease following curative-intent radiation, and not a candidate for surgical salvage due to incurability or morbidity. Note: Patients who decline radical surgery are eligible.
- •For patients with oropharyngeal primary site or unknown primary site only: Patients must have known tumoral HPV status (p16). (Acceptable standards include p16 immunohistochemistry (where a tumor is classified as p16-positive when showing diffuse nuclear and cytoplasmic staining in at least 70% of tumor cells) and/or assessment of HPV DNA.) Note: For these subjects, documentation of p16 status must be submitted with the registration packet.
- •Patients must be cetuximab-resistant by fulfilling at least one of the two criteria defined below:
- •Disease persistence or recurrence within 6 months of completing definitive radiotherapy with concurrent cetuximab for locally advanced disease. Induction chemotherapy, if given, may or may not have included cetuximab.
- •Disease progression during, or within 6 months, of cetuximab treatment in the recurrent and/or metastatic setting.
- •Note: Prior cetuximab exposure may have occurred in any line of therapy (first line, second line, etc.) and is not required to be the most recent therapy received.
- •Patients must be platinum-resistant or platinum-ineligible by fulfilling at least one of the three criteria defined below:
- •Disease persistence or recurrence within 6 months of completing definitive radiotherapy for locally advanced disease, where platinum chemotherapy was administered as a component of induction and/or concurrent systemic treatment.
- •Disease progression during, or within 6 months, of treatment with platinum chemotherapy (e.g., carboplatin or cisplatin) in the recurrent and/or metastatic setting.
- •The patient is not an acceptable candidate for platinum chemotherapy due to medical comorbidities, in the judgment of the local investigator.
- •Note: Prior platinum exposure may have occurred in any line of therapy (first line, second line, etc.) and is not required to be the most recent therapy received.
- •Patients must have prior exposure to an anti-PD1 (programmed cell death protein 1) or anti-PDL1 (programmed cell death ligand 1) monoclonal antibody (mAb), if eligible for immunotherapy in the judgment of the local investigator.
- •Note: Prior exposure to investigational immunotherapies, including anti-CTLA4 (cytotoxic T-lymphocyte-associated antigen 4), anti-OX40, anti-CD40 (cluster of differentiation 40), anti-CD27, anti-TNFR (tumor necrosis factor receptor) antibodies or other investigational immunotherapies, is acceptable.
- •Patients must have Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 at time of informed consent (see Appendix B).
- •Patients must be age ≥ 18 years.
- •Patients must consent to a research biopsy of tumor tissue at baseline, for conduct of correlative studies. In cases where a fresh biopsy is not feasible (i.e., if an accessible tumor site cannot be biopsied with acceptable clinical risk), archival tissue may be submitted instead, after discussion with and approval by the Sponsor-Investigator.
- •Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) criteria, version 1.1 (see section 6) per scan within 28 days prior to registration.
- •Patients must have adequate electrolytes, liver, renal, and hematology function as defined below within 28 days of registration:
- •Absolute neutrophil count (ANC) ≥ 1500/mm3
- •Platelet count (PLT) ≥ 75,000/mm3
- •Creatinine clearance ≥ 30 mL/min per estimated by the Cockraft-Gault formula:
- •Calculated Creatinine Clearance = [(140-age) X (actual body weight in kg) X (0.85 if female)]/(72 X serum creatinine)
- •* Total bilirubin ≤ 1.5 times upper-limit of normal (ULN)
- •AST (aspartate aminotransferase) ≤ 3 times ULN
- •ALT (alanine aminotransferase) ≤ 3 times ULN
- •Magnesium ≥ 1.2 mg/dL or 0.5 mmol/L
- •Corrected Calcium ≥ 8.0 mg/dL or 2.0 mmol/L
- •Potassium ≥ 3.0 mmol/L (Note: Patients may be supplemented to achieve acceptable electrolyte values.)
- •Serum albumin ≥ 25 g/L (≥ 2.5 g/dL)
- •Patients must sign written informed consent prior to beginning study screening procedures. Patients must have the ability to understand and the willingness to sign a written informed consent document.
- •Women of child-bearing potential (WOCBP) must agree to have a pregnancy test within 14 days prior to registration and a repeated test within 3 days of the first dose of ficlatuzumab.
- •Patients must agree to use highly effective contraceptive measures while on study and for 60 days after the last dose of study drug. This includes: Men of reproductive potential AND women of childbearing potential.
- •Effective birth control includes (a) intrauterine device (IUD) plus one barrier method; or (b) 2 barrier methods. Effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm).
- •Exclusion Criteria
- •Nasopharyngeal primary site if WHO Type III (non-keratinizing and EBV-positive as established at the local site).
- •History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational agent.
- •Prior treatment with an HGF/cMet inhibitor such as rilotumumab, crizotinib, MetMAb, or tivantinib (ARQ197).
- •Uncontrolled central nervous system (CNS) metastases, including leptomeningeal metastases, are not allowed.
- •Note: Subjects with previously treated brain metastases will be allowed if the brain metastases have been stable without steroid treatment for at least 2 weeks (radiotherapy or surgery).
- •Failure to recover to Grade 1 or baseline from all toxic effects of previous chemotherapy, radiation therapy, biologic therapy, immunotherapy, and/or experimental therapy, with the exception of:
- 另有 31 项未显示
排除标准
- 未提供
研究组 & 干预措施
Arm I (ficlatuzumab)
Experimental
Patients receive ficlatuzumab IV over 30-60 minutes every 2 weeks in the absence of disease progression or unaccepted toxicity. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Ficlatuzumab (Drug)
Arm II (ficlatuzumab, cetuximab)
Experimental
Patients receive cetuximab IV over 60 -120 minutes and ficlatuzumab IV over 30-60 minutes every 2 weeks in the absence of disease progression or unaccepted toxicity. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Cetuximab (Biological)
Arm II (ficlatuzumab, cetuximab)
Experimental
Patients receive cetuximab IV over 60 -120 minutes and ficlatuzumab IV over 30-60 minutes every 2 weeks in the absence of disease progression or unaccepted toxicity. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Ficlatuzumab (Drug)
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: From the date of randomization until the date of progression or death, assessed up to 2 years
Will be estimated for each arm using a Kaplan-Meier curve.
次要结局
- Percentage of Participants With Dose Limiting Toxicities or Adverse Events(Up to 2 years)
- Overall Response Rate (ORR)(Up to 2 years)
- Overall Survival (OS)(From the date of randomization until the date of death, assessed up to 2 years)
研究者
研究点 (6)
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