A Phase 1b/2 Randomized Study of MEDI-575 in Combination With Carboplatin Plus Paclitaxel Versus Carboplatin Plus Paclitaxel Alone in Adult Subjects With Previously Untreated, Advanced Non-Small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 99
- 试验地点
- 1
- 主要终点
- Number of Participants With Dose Limiting Toxicities (DLT): Phase 1b
研究概览
简要总结
The purpose of this study is to evaluate the dose, antitumor activity, safety and pharmacology of MEDI-575 in combination with carboplatin/paclitaxel in subjects with previously untreated, advanced non-small cell lung cancer (NSCLC).
详细描述
This is a Phase 1b/2, multicenter, open-label study of MEDI-575 to evaluate the dose, anti-tumor activity, safety, and pharmacology (pharmacokinetics, immunogenicity, and biomarkers) of MEDI-575 in combination with carboplatin/paclitaxel in subjects with previously untreated, advanced non-small cell lung cancer. This study has two phases: dose determination (Phase 1b) and randomization (Phase 2).
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 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed inoperable Stage IIIB or Stage IV non-small cell lung cancer according to the Seventh Edition of the American Joint Committee on Cancer (AJCC) Tumor Node Metastases (TNM) staging system (only participants with squamous cell carcinoma will be enrolled)
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Life expectancy of greater than or equal to (>=) 3 months
- •Prothrombin time elevation less than or equal to (<=) Grade 2 by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) criteria (Version 4.0) is acceptable for participants on anticoagulant therapy
- •Adequate hematologic function
- •Adequate organ function
- •Suitable candidates for therapy with carboplatin/paclitaxel
- •Participants must have at least 1 lesion that is measurable using Response Evaluation Criteria for Solid Tumors
- •Participants must be willing to consent to allow collection of archived NSCLC tumor samples
- •Negative serum beta-human chorionic gonadotropin (beta-hCG) test (women of childbearing potential only)
- •Females of childbearing potential, unless surgically sterile has a sterile male partner, is premenarchal or at least 2 years postmenopausal, or practices abstinence, must use 2 effective methods of avoiding pregnancy (including oral, transdermal, or implanted contraceptives, intrauterine device, female condom with spermicide, diaphragm with spermicide, cervical cap, or use of a condom with spermicide by the sexual partner) from screening, and must agree to continue using such precautions for 90 days after the final dose of treatment; cessation of birth control after this point should be discussed with a responsible physician
- •Males, unless surgically sterile, must use 2 effective methods of birth control with a female partner and must agree to continue using such contraceptive precautions from screening through 90 days after the final dose of treatment
排除标准
- •At discretion of the investigator regarding safety of the participants
- •Concurrent enrollment in another clinical study
- •Any concurrent chemotherapy, radiotherapy, immunotherapy, biologic, or hormonal therapy for treatment of cancer
- •Previous monoclonal antibody (mAb) treatment specifically directed against platelet-derived growth factor (PDGF) or PDGF receptors
- •History of serious allergy or reaction to any component of the MEDI-575 formulation
- •Receipt of any previous systemic anticancer therapies for advanced or metastatic disease
- •Previous adjuvant/neoadjuvant radiotherapy or chemotherapy for treatment of previous nonmetastatic disease is allowed provided that 6 months have elapsed from the end of such therapies to the time of enrollment
- •New York Heart Association >= Class II congestive heart failure
- •History of myocardial infarction, unstable angina, transient ischemic attack or stroke within the previous 6 months prior to enrollment
- •History of other invasive malignancy within 5 years except for cervical carcinoma in situ (CIS), non-melanomatous carcinoma of the skin or ductal carcinoma in situ (DCIS) of the breast that have been surgically cured
- •Evidence of active infection requiring the use of systemic antimicrobial treatment within 72 hours prior to initial treatment with MEDI-575
- •Use of immunosuppressive medication (inhaled and topical corticosteroids are permitted) within 7 days prior to enrollment
- •Systemic immunosuppressive steroid therapy
- •Participants may take replacement doses of steroids if on a stable dose for at least 2 weeks prior to enrollment
- •History of active human immunodeficiency virus (HIV) or active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
- •Pregnancy or lactation
- •Previous medical history or evidence of an inter-current illness
- •Any physical, social, or psychiatric condition which would prevent effective cooperation or participation in the study
研究组 & 干预措施
Carboplatin/Paclitaxel
Carboplatin/paclitaxel regimen (carboplatin area under the plasma concentration-time curve [AUC] of 6 milligram per milliliter into minute [mg/mL*min], and paclitaxel 200 milligram per square meter [mg/m^2]) administered as an intravenous (IV) infusion once every 21 days on Day 1, for a total of 6 doses (cycles) until unacceptable toxicity, disease progression, or other reasons for participant withdrawal. Subjects were enrolled from North America/European Union (EU) and Japan regions.
干预措施: Carboplatin (Drug)
Carboplatin/Paclitaxel
Carboplatin/paclitaxel regimen (carboplatin area under the plasma concentration-time curve [AUC] of 6 milligram per milliliter into minute [mg/mL*min], and paclitaxel 200 milligram per square meter [mg/m^2]) administered as an intravenous (IV) infusion once every 21 days on Day 1, for a total of 6 doses (cycles) until unacceptable toxicity, disease progression, or other reasons for participant withdrawal. Subjects were enrolled from North America/European Union (EU) and Japan regions.
干预措施: Paclitaxel (Drug)
Carboplatin/Paclitaxel + MEDI-575
Carboplatin/paclitaxel regimen (carboplatin AUC = 6 mg/mL*min, and paclitaxel 200 mg/m^2) followed by MEDI-575 at a dose of 25 milligram per kilogram (mg/kg) administered as an IV infusion once every 21 days on Day 1 for a total of 6 cycles until unacceptable toxicity, disease progression, initiation of alternative anticancer therapy, or other reasons for participant withdrawal. MEDI-575 alone continued in those participants who achieved stable disease or better at the completion of carboplatin/paclitaxel therapy and did not demonstrate toxicity to MEDI-575. Subjects were enrolled from North America/European Union (EU) and Japan regions.
干预措施: Carboplatin (Drug)
Carboplatin/Paclitaxel + MEDI-575
Carboplatin/paclitaxel regimen (carboplatin AUC = 6 mg/mL*min, and paclitaxel 200 mg/m^2) followed by MEDI-575 at a dose of 25 milligram per kilogram (mg/kg) administered as an IV infusion once every 21 days on Day 1 for a total of 6 cycles until unacceptable toxicity, disease progression, initiation of alternative anticancer therapy, or other reasons for participant withdrawal. MEDI-575 alone continued in those participants who achieved stable disease or better at the completion of carboplatin/paclitaxel therapy and did not demonstrate toxicity to MEDI-575. Subjects were enrolled from North America/European Union (EU) and Japan regions.
干预措施: Paclitaxel (Drug)
Carboplatin/Paclitaxel + MEDI-575
Carboplatin/paclitaxel regimen (carboplatin AUC = 6 mg/mL*min, and paclitaxel 200 mg/m^2) followed by MEDI-575 at a dose of 25 milligram per kilogram (mg/kg) administered as an IV infusion once every 21 days on Day 1 for a total of 6 cycles until unacceptable toxicity, disease progression, initiation of alternative anticancer therapy, or other reasons for participant withdrawal. MEDI-575 alone continued in those participants who achieved stable disease or better at the completion of carboplatin/paclitaxel therapy and did not demonstrate toxicity to MEDI-575. Subjects were enrolled from North America/European Union (EU) and Japan regions.
干预措施: MEDI-575 (Drug)
结局指标
主要结局
Number of Participants With Dose Limiting Toxicities (DLT): Phase 1b
时间窗: From Day 1 to Day 21 of first cycle
A DLT was defined as: 1. Any treatment-related Grade 3 or higher non-hematologic toxicity that occurred during the DLT assessment period with the following exceptions: 1. Grade 3 fever (in the absence of neutropenia) defined as more than (\>) 40.0 degree Celcius (\> 104.0 degree Fahrenheit) that resolved to normal or baseline within 24 hours of treatment and was not considered a serious adverse event (SAE); or 2. Grade 3 rigors/chills that responded to optimal therapy. 2. Any treatment-related Grade 3 or higher hematologic toxicity.
Progression Free-Survival (PFS)
时间窗: From randomization until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years)
Progression-free survival defined as the time from randomization (randomization referred to the date of treatment assignment) to disease progression (defined according to Response Evaluation Criteria for Solid Tumors \[RECIST\] version 1.1 guidelines) or death due to any cause, whichever occurs first. Participants without progression or death at the time of analysis were censored at their last date of tumor evaluation. PFS was assessed only in North America/European Union (EU) participants. Progression-free survival was evaluated using Kaplan-Meier method.
次要结局
- Maximum Serum Concentration at Steady State (Cmax,ss) of MEDI-575(Cycle 1 (pre-infusion and end of infusion on Day 1, Day 2, Day 8, and Day 15); Day 1 of Cycles 2 to 4 (pre-infusion and end of infusion))
- Best Overall Response(From initiation of treatment until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years))
- Objective Response Rate (ORR)(From initiation of treatment until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years))
- Duration of Response (DR)(From initiation of treatment until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years))
- Time to Response (TTR)(From initiation of treatment until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years))
- Time of Maximal Observed Concentration (Tmax) of MEDI-575 After First Dose(Day 1 (pre-infusion and end of infusion), Day 2 (24 hours post Day 1 infusion), Day 8, and Day 15)
- Area Under the Concentration-Time Curve Over the Dosing Interval (AUCtau) of MEDI-575 After First Dose(Day 1 (pre-infusion and end of infusion), Day 2 (24 hours post Day 1 infusion), Day 8, and Day 15)
- Number of Participants With Platelet-derived Growth Factor Receptor Alpha (PDGFRα) Expression in Tumor Cells of Archived Tumor Samples(Baseline (Screening [Days -28 to -1]))
- Time to Progression (TTP)(From initiation of treatment until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years))
- Overall Survival (OS)(From initiation of treatment until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years))
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(From signing of informed consent form until 90 days post the last dose treatment (approximately 3 years))
- Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs(From signing of informed consent form until 90 days post the last dose treatment (approximately 3 years))
- Trough Serum Concentration at Steady State (Ctrough,ss) of MEDI-575(Cycle 1 (pre-infusion and end of infusion on Day 1, Day 2, Day 8, and Day 15); Day 1 of Cycles 2 to 4 (pre-infusion and end of infusion))
- Percentage of Participants With Positive Anti-MEDI-575 Antibodies(Day 1 (prior to infusion) of Cycles 1 to 7 (21-day cycle), end of treatment, 30 and 60 days after the last dose (approximately 3 years))
- Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as AEs(From signing of informed consent form until 90 days post the last dose treatment (approximately 3 years))
- Maximum Observed Serum Concentration (Cmax) of MEDI-575 After First Dose(Day 1 (pre-infusion and end of infusion), Day 2 (24 hours post Day 1 infusion), Day 8, and Day 15)
- Time to Maximum Serum Concentration at Steady State (Tmax,ss) of MEDI-575(Cycle 1 (pre-infusion and end of infusion on Day 1, Day 2, Day 8, and Day 15); Day 1 of Cycles 2 to 4 (pre-infusion and end of infusion))
- Number of Participants With PDGFRα Expression in Stromal Cells of Archived Tumor Samples(Baseline (Screening [Days -28 to -1]))