I-SPY Trial (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 5,000
- 试验地点
- 78
- 主要终点
- Determine whether adding experimental agents to standard neoadjuvant medications increases the probability of pathologic complete response (pCR) over standard neoadjuvant chemotherapy for each biomarker signature established at trial entry.
研究概览
简要总结
The purpose of this study is to further advance the ability to practice personalized medicine by learning which new drug agents are most effective with which types of breast cancer tumors and by learning more about which early indicators of response (tumor analysis prior to surgery via magnetic resonance imaging (MRI) images along with tissue and blood samples) are predictors of treatment success.
详细描述
I-SPY2 will assess the efficacy of novel drugs in sequence with standard chemotherapy. The goal is identify treatment strategies for subsets on the basis of molecular characteristics (biomarker signatures) of their disease with high estimated pCR rate. As described for previous adaptive trials, novel regimens with sufficiently high activities alone and contribute to treatment strategies that show a high Bayesian predictive probability of being more effective than the dynamic control will graduate from the trial with their corresponding biomarker signature(s). Treatment strategies will be dropped if they show a low probability of improved efficacy with any biomarker signature. New drugs will enter as those that have undergone testing complete their evaluation.
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
- •Histologically confirmed invasive cancer of the breast
- •Clinically or radiologically measureable disease in the breast after diagnostic biopsy, defined as longest diameter greater than or equal to 25 mm (2.5cm)
- •No prior cytotoxic regimens are allowed for this malignancy. Patients may not have had prior chemotherapy or prior radiation therapy to the ipsilateral breast for this malignancy. Prior bis-phosphonate therapy is allowed
- •Age ≥18 years
- •ECOG performance status 0-1
- •Willing to undergo core biopsy of the primary breast lesion to assess baseline biomarkers
- •Non-pregnant and non-lactating
- •No ferromagnetic prostheses. Patients who have metallic surgical implants that are not compatible with an MRI machine are not eligible.
- •Ability to understand and willingness to sign a written informed consent (I-SPY TRIAL Screening Consent)
- •Eligible tumors must meet one of the following criteria: Stage II or III, or T4, any N, M0, including clinical or pathologic inflammatory cancer or Regional Stage IV, where supraclavicular lymph nodes are the only sites metastasis
- •Any tumor ER/PgR status, any HER-2/neu status as measured by local hospital pathology laboratory and meets any tumor assay profile described in protocol section 4.1.2F
- •Normal organ and marrow function: Leukocytes ≥ 3000/μL, Absolute neutrophil count ≥ 1500/μL, Platelets ≥ 100,000/μL, Total bilirubin within normal institutional limits, unless patient has Gilbert's disease, for which bilirubin must be ≤ 2.0 x ULN, AST(SGOT)/ALT (SGPT) ≤ 1.5 x institutional ULN, creatinine < 1.5 x institutional ULN
- •No uncontrolled or severe cardiac disease. Baseline ejection fraction (by nuclear imaging or echocardiography) must by ≥ 50%
- •No clinical or imaging evidence of distant metastases by PA and Lateral CXR, Radionuclide Bone scan, and LFTs including total bilirubin, ALT, AST, and alkaline phosphatase
- •Tumor assay profile must include on of the following: MammaPrint High, any ER status, any HER2 status, or MammaPrint Low, ER negative (<5%), any HER2 status, or MammaPrint Low, ER positive, HER2/neu positive by any one of the three methods used (IHC, FISH, TargetPrint™)
- •Ability to understand and willingness to sign a written informed consent document (I-SPY 2 TRIAL Consent #2)
排除标准
- •Use of any other investigational agents within 30 days of starting study treatment
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to the study agent or accompanying supportive medications.
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
研究组 & 干预措施
Pembrolizumab 8 cycle
Arm is closed.
干预措施: Pembrolizumab - 8 cycle (Drug)
Ganetespib
Arm is closed.
干预措施: Ganetespib (Drug)
PLX3397
Arm is closed.
干预措施: PLX3397 (Drug)
Pembrolizumab 4 cycle
Arm is closed.
干预措施: Pembrolizumab - 4 cycle (Drug)
Talazoparib plus Irinotecan
Arm is closed.
干预措施: Talazoparib plus Irinotecan (Drug)
Pertuzumab and Trastuzumab
Arm is closed. Novel Control Investigational Agent.
干预措施: Pertuzumab and Trastuzumab (Drug)
SGN-LIV1A
Arm is closed.
干预措施: SGN-LIV1A (Drug)
Endocrine Optimization Pilot: Amcenestrant + Letrozole
Arm is closed. Novel Investigational Agent.
干预措施: Amcenestrant + Letrozole (Drug)
Zanidatamab for Block ABC
Arm open for accrual. Novel investigational Agent.
干预措施: Zanidatamab (Drug)
Neratinib
Arm is closed.
干预措施: Neratinib (Drug)
Durvalumab plus Olaparib
Arm is closed.
干预措施: Durvalumab plus Olaparib (Drug)
ABT-888
Arm is closed.
干预措施: ABT-888 (Drug)
Endocrine Optimization Pilot: Amcenestrant Monotherapy
Arm is closed. Novel Investigational Agent.
干预措施: Amcenestrant (Drug)
Endocrine Optimization Pilot: (Z)-Endoxifen + Abemaciclib
Arm is closed for accrual. Enrollment completed. Novel investigational Agent.
干预措施: Endoxifen + Abemaciclib (Drug)
Rilvegostomig + TDXd in Block A and followed by SOC in Block B
Arm is closed for accrual. Novel investigational Agent.
干预措施: Rilvegostomig + TDXd (Drug)
DAN222 + Niraparib in Block A and followed by SOC in Block B
Arm is closed for accrual. Novel investigational Agent.
干预措施: Dan222 + Niraparib (Drug)
Sarilumab + Cemiplimab + Paclitaxel in Block B followed by SOC Block C
Arm is closed for accrual. Novel investigational Agent.
干预措施: Sarilumab + Cemiplimab + Paclitaxel (Drug)
GSK 5733584 in Block A and followed by SOC in Block B
Arm is open for accrual. Novel Investigational Agent.
干预措施: GSK 5733584 (Drug)
Standard Therapy
Paclitaxel, Herceptin followed by Doxorubicin and Cyclophosphamide treatment depending on HR/HER-2 status.
干预措施: Standard Therapy (Drug)
AMG 386 with or without Trastuzumab
Arm is closed.
干预措施: AMG 386 with or without Trastuzumab (Drug)
AMG 386 with or without Trastuzumab
Arm is closed.
干预措施: AMG 386 and Trastuzumab (Drug)
AMG 479 plus Metformin
Arm is closed.
干预措施: AMG 479 (Ganitumab) plus Metformin (Drug)
MK-2206 with or without Trastuzumab
Arm is closed.
干预措施: MK-2206 with or without Trastuzumab (Drug)
T-DM1 and Pertuzumab
Arm is closed.
干预措施: T-DM1 and Pertuzumab (Drug)
Patritumab with or without Trastuzumab
Arm is closed.
干预措施: Patritumab and Trastuzumab (Drug)
SD-101 + Pembrolizumab
Arm is closed.
干预措施: SD-101 + Pembrolizumab (Drug)
Tucatinib
Arm is closed.
干预措施: Tucatinib plus trastuzumab and pertuzumab (Drug)
Cemiplimab
Arm is closed. Novel Investigational Agent.
干预措施: Cemiplimab (Drug)
Cemiplimab plus REGN3767
Arm is closed. Novel Investigational Agent.
干预措施: Cemiplimab plus REGN3767 (Drug)
Trilaciclib with or without trastuzumab + pertuzumab
Arm is closed. Novel Investigational Agent.
干预措施: Trilaciclib with or without trastuzumab + pertuzumab (Drug)
SYD985 ([vic-]trastuzumab duocarmazine)
Arm is closed. Novel Investigational Agent.
干预措施: SYD985 ([vic-]trastuzumab duocarmazine) (Drug)
GSK 5733584 + Dostarlimab in Block A and followed by SOC in Block B
Arm is open for accrual. Novel Investigational Agent.
干预措施: GSK 5733584 + Dostarlimab (Drug)
Oral Paclitaxel + Encequidar + Dostarlimab (TSR-042) + Carboplatin with or without trastuzumab
Arm is closed. Novel Investigational Agent.
干预措施: Oral Paclitaxel + Encequidar + Dostarlimab (TSR-042) + Carboplatin with or without trastuzumab (Drug)
Oral Paclitaxel + Encequidar + Dostarlimab (TSR-042) with or without trastuzumab
Arm is closed. Novel Investigational Agent.
干预措施: Oral Paclitaxel + Encequidar + Dostarlimab (TSR-042) with or without trastuzumab (Drug)
Endocrine Optimization Pilot: Amcenestrant + Abemaciclib
Arm is closed. Novel Investigational Agent.
干预措施: Amcenestrant + Abemaciclib (Drug)
ARX788 in Block A and followed by SOC in Block B
Arm is closed for accrual for accrual. Novel investigational Agent followed by SOC.
干预措施: ARX788 (Drug)
ARX788 + Cemiplimab in Block A and followed by SOC in Block B
Arm is closed for accrual. Novel investigational Agent followed by SOC.
干预措施: ARX788 + Cemiplimab (Drug)
VSV-IFNβ-NIS (VOYAGER V1™; VV1) + Cemiplimab in Block A and followed by SOC in block B
Arm is closed for accrual. Novel investigational Agent followed by SOC.
干预措施: VV1 + Cemiplimab (Drug)
Datopotamab Deruxtecan in Block A and followed by SOC in block B
Arm is closed for accrual. Novel investigational Agent followed by SOC.
干预措施: Datopotamab deruxtecan (Drug)
Datopotamab Deruxtecan + Durvalumab in Block A and followed by SOC in block B
Arm is closed for accrual. Novel investigational Agent followed by SOC.
干预措施: Datopotamab deruxtecan + Durvalumab (Drug)
Endocrine Optimization Pilot: Lasofoxifene
Arm is closed for accrual. Novel investigational Agent.
干预措施: Lasofoxifene (Drug)
Endocrine Optimization Pilot: (Z)-Endoxifen
Arm is closed for accrual. Novel investigational Agent.
干预措施: Z-endoxifen (Drug)
Endocrine Optimization Pilot: ARV-471
Arm is closed for accrual. Novel investigational Agent.
干预措施: ARV-471 (Drug)
Endocrine Optimization Pilot: ARV-471 + Letrozole
Arm is closed for accrual. Novel investigational Agent.
干预措施: ARV-471 + Letrozole (Drug)
Endocrine Optimization Pilot: ARV-471 + Abemaciclib
Arm is closed for accrual. Novel investigational Agent.
干预措施: ARV-471 + Abemaciclib (Drug)
Ivonescimab in Blocks A and B
Open for accrual. Novel Investigational Agent.
干预措施: Ivonescimab (20mg/kg Q3W) (Drug)
结局指标
主要结局
Determine whether adding experimental agents to standard neoadjuvant medications increases the probability of pathologic complete response (pCR) over standard neoadjuvant chemotherapy for each biomarker signature established at trial entry.
时间窗: Post surgery based on upto 36-week treatment
次要结局
- Establishing predictive and prognostic indices based on qualification and exploratory markers to predict pCR and residual cancer burden (RCB).(Blood and Tissue Collection: Baseline, Post-Randomization, Pre-AC, Pre- and Post-Surgery)
- To determine three- and five-year relapse-free survival (RFS) and OS among the treatment arms.(Three- and Five-Year Post-surgery Follow-up)
- MRI Volume(Four time points during the on-study phase: Baseline, Post-randomization, Pre-AC treatment and Pre-Surgery)
- To determine incidence of adverse events (AEs), serious adverse events (SAEs), and laboratory abnormalities of each investigational agent tested.(Post-Randomization, Pre-AC, Pre-Surgery, Post-Surgery upto One Year during follow-up)