A Phase 1b Open-Label Study of the Safety and Pharmacokinetics of MEHD7945A in Combination With Either Cisplatin and 5-FU or Paclitaxel and Carboplatin in Patients With Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 6
- 主要终点
- Percentage of Participants with Adverse Events
研究概览
简要总结
This open-label, multicenter study will evaluate the safety, tolerability, and pharmacokinetics of MEHD7945A in combination with chemotherapy (either cisplatin plus 5-FU or carboplatin plus paclitaxel) in participants with previously untreated R/M SCCHN. There are two stages for each arm in this study: a Dose-limiting Toxicity (DLT)-evaluation stage (Stage I) and a cohort-expansion stage (Stage II). In Stage I, DLTs will be assessed during a DLT Assessment Window of 21 days (i.e., Cycle 1 Day 1 through Cycle 1 Day 21) for both arms. In Stage II, participants will be enrolled to further characterize the safety, pharmacokinetics, and anti-tumor activity of MEHD7945A in combination with cisplatin + 5-FU or carboplatin + paclitaxel at the identified recommended Phase II dose.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Histologically confirmed R/M SCCHN of mucosal origin (e.g., oral cavity, oropharynx, hypopharynx, larynx) that is not amenable to further curative local therapy (e.g., surgery, radiation including re-irradiation) (1L R/M)
- •Participants with unknown primary SCCHN presumed to be of head and neck mucosal origin are eligible if they meet all other entry criteria
- •For participants who present with de novo metastatic disease, no prior systemic chemotherapy is allowed
- •For participants with recurrent SCCHN, prior systemic therapy is allowed if it was given as part of induction or definitive therapy. If participants have received prior combined chemo-radiation therapy, they must be off therapy for at least 3 months
- •Consent to provide archival tumor tissue for biomarker testing
- •Life expectancy greater than or equal to (>/=) 12 weeks
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- •Disease that is measurable per modified RECIST v1.1
- •Adequate bone marrow and organ function
排除标准
- •Nasopharyngeal cancer
- •Prior treatment with an investigational or approved agent for the purpose of inhibiting human epidermal growth factor receptor (HER) family members. This includes, but is not limited to, cetuximab, panitumumab, erlotinib, gefitinib, and lapatinib
- •Prior treatment with an epidermal growth factor receptor (EGFR) inhibitor is allowed if it was administered as part of definitive therapy for locally advanced disease and completed/terminated >/= 3 months before study enrollment
- •Major surgical procedure within 4 weeks prior to Day 1
- •Leptomeningeal disease as the only manifestation of the current malignancy
- •Active infection requiring antibiotics
- •Active autoimmune disease that is not controlled by nonsteroidal anti-inflammatory drugs (NSAIDs)
- •Symptomatic hypercalcemia requiring continued use of bisphosphonate therapy
- •Current severe, uncontrolled systemic disease
- •History of cardiac heart failure of New York Heart Association Class II or greater or serious cardiac arrhythmia requiring treatment (except for atrial fibrillation and paroxysmal supraventricular tachycardia)
- •History of myocardial infarction within 6 months prior to Cycle 1, Day 1, or history of unstable angina
- •Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
- •History of bleeding diathesis or coagulopathy other than that due to anticoagulation therapy
- •Clinically significant gastrointestinal (GI) bleeding within 6 months prior to Cycle 1, Day 1
- •History of interstitial lung disease (ILD)
- •History of severe (Grade 3 or 4) allergic or hypersensitivity reaction to therapeutic antibodies that required discontinuation of therapy
- •Known human immunodeficiency virus (HIV) infection
- •Untreated/active central nervous system (CNS) metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control)
- •Pregnant or lactating women
- •Malignancies other than SCCHN within 5 years prior to enrollment, with the exception of adequately treated basal or squamous cell skin cancer and carcinoma in situ of the cervix or skin (e.g., melanoma in situ) or indolent prostate cancer
研究组 & 干预措施
A: MEHD7945A+ Cisplatin + 5-FU
Participants with previously untreated R/M SCCHN will receive MEHD7945A 1650 milligrams (mg) intravenous (IV) infusion on Day 1 of each 21-day cycle until disease progression, unacceptable toxicity, or protocol violation. Cisplatin will be administered as 100 milligrams per square meter (mg/m^2) IV infusion on Day 1 of Cycles 1 to 6. 5-FU will be administered as 1000 mg/m^2/day administered as continuous infusion over Days 1-4 of Cycles 1 to 6.
干预措施: 5-FU (Drug)
A: MEHD7945A+ Cisplatin + 5-FU
Participants with previously untreated R/M SCCHN will receive MEHD7945A 1650 milligrams (mg) intravenous (IV) infusion on Day 1 of each 21-day cycle until disease progression, unacceptable toxicity, or protocol violation. Cisplatin will be administered as 100 milligrams per square meter (mg/m^2) IV infusion on Day 1 of Cycles 1 to 6. 5-FU will be administered as 1000 mg/m^2/day administered as continuous infusion over Days 1-4 of Cycles 1 to 6.
干预措施: Cisplatin (Drug)
A: MEHD7945A+ Cisplatin + 5-FU
Participants with previously untreated R/M SCCHN will receive MEHD7945A 1650 milligrams (mg) intravenous (IV) infusion on Day 1 of each 21-day cycle until disease progression, unacceptable toxicity, or protocol violation. Cisplatin will be administered as 100 milligrams per square meter (mg/m^2) IV infusion on Day 1 of Cycles 1 to 6. 5-FU will be administered as 1000 mg/m^2/day administered as continuous infusion over Days 1-4 of Cycles 1 to 6.
干预措施: MEHD7945A (Drug)
B: MEHD7945A + Paclitaxel + Carboplatin
Participants with previously untreated R/M SCCHN will receive MEHD7945A 1650 mg IV infusion on Day 1 of each 21-day cycle until disease progression, unacceptable toxicity, or protocol violation. Carboplatin will be administered at a dose to achieve an area under the curve (AUC) of 6 milligrams/milliliter/minute (mg/mL/min) as an IV infusion on Day 1 of Cycles 1 to 6. Paclitaxel will be administered as 200 mg/m^2 IV infusion on Day 1 of Cycles 1 to 6.
干预措施: Carboplatin (Drug)
B: MEHD7945A + Paclitaxel + Carboplatin
Participants with previously untreated R/M SCCHN will receive MEHD7945A 1650 mg IV infusion on Day 1 of each 21-day cycle until disease progression, unacceptable toxicity, or protocol violation. Carboplatin will be administered at a dose to achieve an area under the curve (AUC) of 6 milligrams/milliliter/minute (mg/mL/min) as an IV infusion on Day 1 of Cycles 1 to 6. Paclitaxel will be administered as 200 mg/m^2 IV infusion on Day 1 of Cycles 1 to 6.
干预措施: MEHD7945A (Drug)
B: MEHD7945A + Paclitaxel + Carboplatin
Participants with previously untreated R/M SCCHN will receive MEHD7945A 1650 mg IV infusion on Day 1 of each 21-day cycle until disease progression, unacceptable toxicity, or protocol violation. Carboplatin will be administered at a dose to achieve an area under the curve (AUC) of 6 milligrams/milliliter/minute (mg/mL/min) as an IV infusion on Day 1 of Cycles 1 to 6. Paclitaxel will be administered as 200 mg/m^2 IV infusion on Day 1 of Cycles 1 to 6.
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Percentage of Participants with Adverse Events
时间窗: From Baseline until 45 days after last dose of study drug or until initiation of another anti-cancer therapy, withdrawal or lost to follow-up, whichever occurs first (up to approximately 3 years)
Percentage of Participants With DLTs
时间窗: Cycle 1 Day 1 through Cycle 1 Day 21 (Cycle length = 3 weeks)
次要结局
- Minimum Serum Concentration (Cmin) of MEHD7945A(Pre-infusion (0 hour) on Day 1 of Cycles 1, 2, 3, 4, and 8 (each cycle = 3 weeks))
- Percentage of Participants With Disease Control (CR or PR or Stable Disease [SD]) as Assessed by Modified RECIST v1.1 Criteria(From first dose of study drug until disease progression or death (up to approximately 3 years))
- Area Under Concentration-Time Curve From 0 to 6 Hours (AUC0-6h) of Cisplatin(Pre-infusion (0 hour), 0 to 5 minutes and 1, 2, 4, 6 hours post-infusion (infusion duration = 1-2 hours) on Day 1 of Cycle 1 (Cycle length = 3 weeks))
- Plasma Half-Life (t1/2) of Paclitaxel(Pre-infusion (0 hour), 0 to 5 minutes and 1, 3, 5 hours post-infusion (infusion duration = 3 hours) on Day 1 of Cycle 1, Day 2 of Cycle 1 (Cycle length = 3 weeks))
- Percentage of Participants With Objective Response (Complete Response [CR] or Partial Response [PR]) as Assessed by Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)(From first dose of study drug until disease progression or death (up to approximately 3 years))
- Progression-Free Survival as Assessed by Modified RECIST v1.1 Criteria(From first dose of study drug until disease progression or death (up to approximately 3 years))
- Maximum Serum Concentration (Cmax) of MEHD7945A(30 minutes and 4 hours post-infusion (infusion duration=90 minutes) on Day 1 of Cycle 1; 30 min post-infusion on Day 1 of Cycles 2, 3, 4, and 8 (each cycle = 3 weeks))
- Duration of Objective Response (CR or PR) as Assessed by Modified RECIST v1.1 Criteria(From first occurrence of CR or PR until relapse or death (up to approximately 3 years))
- Cmax of Cisplatin(Pre-infusion (0 hour), 0 to 5 minutes and 1, 2, 4, 6 hours post-infusion (infusion duration = 1-2 hours) on Day 1 of Cycle 1 (Cycle length = 3 weeks))
- AUC0-6h of Carboplatin(Pre-infusion (0 hour), 0 to 5 minutes and 1, 2, 4, 6 hours post-infusion (infusion duration = 15-30 minutes) on Day 1 of Cycle 1 (Cycle length = 3 weeks))
- Cmax Normalized by Dose (Cmax/D) of Carboplatin(Pre-infusion (0 hour), 0 to 5 minutes and 1, 2, 4, 6 hours post-infusion (infusion duration = 15-30 minutes) on Day 1 of Cycle 1 (Cycle length = 3 weeks))
- AUC0-6h Normalized by Dose (AUC0-6h/D) of Carboplatin(Pre-infusion (0 hour), 0 to 5 minutes and 1, 2, 4, 6 hours post-infusion (infusion duration = 15-30 minutes) on Day 1 of Cycle 1 (Cycle length = 3 weeks))
- Cmax of Paclitaxel(Pre-infusion (0 hour), 0 to 5 minutes and 1, 3, 5 hours post-infusion (infusion duration = 3 hours) on Day 1 of Cycle 1, Day 2 of Cycle 1 (Cycle length = 3 weeks))
- Percentage of Participants With Anti-Therapeutic Antibodies to MEHD7945A(Pre-dose (0 hour) on Day 1 of Cycles 1, 4, 8 (each cycle = 3 weeks) and at study completion (approximately 3 years))
- Area Under Concentration-Time Curve From Day 1 to 21 (AUC0-21d) of MEHD7945A(Pre-infusion (0 hour), 30 minutes post-infusion (infusion duration=90 minutes) on Day 1 of Cycles 1, 2, 3, 4, 8; 4 hours post-infusion on Day 1 of Cycle 1; Days 2, 4, 8, 15 of Cycle 1 (each cycle = 3 weeks))
- Plasma Concentrations of 5-FU(Pre-infusion (0 hour) on Day 1 of Cycle 1; Day 2 of Cycle 1 (Cycle length = 3 weeks))
- Cmax of Carboplatin(Pre-infusion (0 hour), 0 to 5 minutes and 1, 2, 4, 6 hours post-infusion (infusion duration = 15-30 minutes) on Day 1 of Cycle 1 (Cycle length = 3 weeks))
- Area Under Concentration-Time Curve From 0 to 24 Hours (AUC0-24h) of Paclitaxel(Pre-infusion (0 hour), 0 to 5 minutes and 1, 3, 5 hours post-infusion (infusion duration = 3 hours) on Day 1 of Cycle 1, Day 2 of Cycle 1 (Cycle length = 3 weeks))