A Phase 1b/2 Study of OMP-59R5 in Combination With Etoposide and Platinum Therapy in Subjects With Untreated Extensive Stage Small Cell Lung Cancer (PINNACLE)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 172
- 试验地点
- 35
- 主要终点
- Phase 1b: Overall Response (Response Evaluable Population)
研究概览
简要总结
The study consists of a Phase1b lead-in portion to determine the maximum tolerated dose (MTD) of OMP-59R5 (tarextumab) in combination with etoposide (EP) for 6 cycles followed a Phase 2, multi center, randomized, placebo-controlled portion comparing the efficacy and safety of OMP-59R5 in combination with EP for 6 cycles followed by single agent OMP-59R5 relative to EP alone for 6 cycles in subjects receiving first-line therapy for extensive stage small cell lung cancer.
详细描述
The Phase 1b lead-in portion of the study was conducted to determine the MTD of OMP-59R5 administered along with EP. The Phase 2 portion of the study was multi-center, randomized, and placebo-controlled. Subjects who qualified for enrollment into the Phase 2 portion of the study were randomized in a 1:1 ratio to receive study treatment of tarextumab along with EP (Arm A) or placebo along with EP (Arm B).
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must meet all of the following criteria to be eligible for the study:
- •Histologically or cytologically documented extensive stage small cell lung cancer.
- •Adults of 18 years of age or older.
- •Performance Status (ECOG) of 0 or
- •Formalin Fixed Paraffin Embedded (FFPE) tumor tissue.
- •Adequate organ function:
- •Adequate hematologic function (absolute neutrophil count [ANC] ≥ 1,500 cells/μL; hemoglobin ≥ 9 g/dL, platelets ≥ 100,000/μL).
- •Adequate renal function (serum creatinine ≤ 1.5 mg/dL or calculated creatinine clearance ≥ 60 mL/min using Cockcroft-Gault formula).
- •Adequate hepatic function (alanine aminotransferase [ALT] ≤ 3 x upper limit of normal [ULN], ALT may be ≤ 5 x ULN if due to liver metastases but cannot be associated with concurrent elevated bilirubin >1.5 times the upper limit of normal (ULN) unless it is approved by the Sponsor's Medical Monitor).
- •Prothrombin Time (PT)/International Normalized Ration (INR) ≤1.5 × ULN, activated partial thromboplastin time (aPTT) ≤1.5 × ULN.
- •Written consent on an Institutional Review Board (IRB)/IndependentEthics Committee (IEC)-approved Informed Consent Form prior to any study-specific evaluation.
- •For women of child-bearing potential, negative serum pregnancy test at screening and use of physician-approved method of birth control from 30 days prior to the first study drug administration to 30 days following the last study drug administration or the last EP in the study, whichever is discontinued last.
- •Male subjects must be surgically sterile or must agree to use physician-approved contraception during the study and for 30 days following the last study drug administration or the last EP in the study, whichever is discontinued last.
排除标准
- •Subjects who meet any of the following criteria will not be eligible for participation in the study:
- •Limited stage small cell lung cancer appropriate for radical treatment with chemoradiation.
- •Prior therapy including radiation, chemotherapy or surgery for newly diagnosed extensive stage small cell lung cancer.
- •Presence of any serious or uncontrolled illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure unstable angina pectoris, uncontrolled cardiac arrhythmia, uncontrolled arterial thrombosis, symptomatic pulmonary embolism, and psychiatric illness that would limit compliance with study requirement.
- •History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty and/or stenting within 6 months prior to the first administration of study drug.
- •A history of malignancy with the exception of:
- •Adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or in situ cervical cancer
- •Adequately treated stage I cancer from which the subject is currently in remission, or
- •Any other cancer from which the subject has been disease-free for ≥ 3 years
- •Known human immunodeficiency virus (HIV) infection.
- •Females who are pregnant or breastfeeding.
- •Concurrent use of therapeutic warfarin (prophylactic low dose of warfarin, i.e., 1 mg daily for port catheter is allowed)
研究组 & 干预措施
OMP-59R5 Combination with Etoposide and Cisplatin
干预措施: OMP-59R5 (Drug)
OMP-59R5 Combination with Etoposide and Cisplatin
干预措施: Etoposide (Drug)
OMP-59R5 Combination with Etoposide and Cisplatin
干预措施: Placebo (Drug)
OMP-59R5 Combination with Etoposide and Cisplatin
干预措施: Cisplatin or Carboplatin (Drug)
Etoposide and Cisplatin plus Placebo
干预措施: OMP-59R5 (Drug)
Etoposide and Cisplatin plus Placebo
干预措施: Etoposide (Drug)
Etoposide and Cisplatin plus Placebo
干预措施: Placebo (Drug)
Etoposide and Cisplatin plus Placebo
干预措施: Cisplatin or Carboplatin (Drug)
结局指标
主要结局
Phase 1b: Overall Response (Response Evaluable Population)
时间窗: Up to 1 year in absence of unacceptable toxicity or disease progression.
The best overall response is defined as the best Investigator-assessed response recorded from the start of the treatment until disease progression in the following order of importance: Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD), Not Evaluable (NE). Response evaluable population includes subjects who received 1 partial dose of OMP-59R5 and at at least 1 post tumor assessment.
Phase 1b: To Determine the Maximum Tolerated Dose (MTD) of OMP-59R5 When Administered With Etoposide and Cisplatin or Carboplatin (Number of Subjects With DLTs)
时间窗: Up to 1 year in absence of unacceptable toxicity or disease progression.
To determine the MTD of tarextumab when administered on Day 1 of each 21 day cycle along with etoposide 100 mg/m2 on Days 1, 2 and 3, and cisplatin 80 mg/m2 or carboplatin area under the curve (AUC) of 5 mg/mL•min on Day 1 in subjects with untreated extensive stage small cell lung cancer. DLT evaluable population includes all subjects who received at least 1 partial dose of OMP-59R5 during the Phase 1b dose escalation portion of the study including the carboplatin cohort and who had completed Day 21 cycle of 1 OMP-59R5 administration or had discontinued due to drug-related toxicity.
Phase 2: Progression Free Survival (ITT Population)
时间窗: Up to 1 year until disease progression or death.
To determine the improvement in Progression Free Survival (PFS) resulting from the addition of tarextumab to etoposide and platinum therapy (EP) in subjects receiving first-line therapy for extensive stage small cell lung cancer. PFS is based on the Investigator-assessments of tumor response which is defined as the number of days from randomization until death or disease progression as defined by RECIST criteria for the ITT Population.
Phase 2: Best Overall Tumor Response Based on Investigator Assessment (ITT Population)
时间窗: Up to 1 year in absence of unacceptable toxicity or disease progression
The response rate is the number of subjects per treatment arm who have either a complete response (CR) or partial response (PR) for best overall response (according to RECIST criteria) divided by the number of subjects randomized to the respective arms.
次要结局
未报告次要终点