PANGEA: Personalized Antibodies for Gastro-Esophageal Adenocarcinoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Overall Survival
研究概览
简要总结
The purpose of this study is to determine if doctors can use the results of special tests of subjects tumor tissue, that will look for specific abnormalities in the tumor, to choose a specific drug that is targeted to work against that abnormality (called molecular profiling) and to see what effects (good and/or bad) that targeted drug has on subjects cancer when it is given with standard chemotherapy.
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 metastatic gastric or esophagogastric junction (type I,II,III Siewert) adenocarcinoma
- •Newly-diagnosed chemo-naïve or recurrent after curative-intent surgery
- •>6 months after completion of adjuvant therapy (including chemotherapy and/or radiotherapy)
- •No prior treatment with any targeted agent
- •Patients who have started first line mFOLFOX6 therapy (+/-trastuzumab for HER2 amplified tumors) may be considered for trial participation if they have received no more than 4 doses of therapy at the time of consent and screening.
- •Measurable metastatic disease by RECIST criteria,
- •Must be amenable to ultrasound or CT-guided biopsy of one metastatic lesion
- •Peritoneal disease as the sole site of occult metastasis or presenting as malignant ascites is acceptable if a cell block of tumor cells can be obtained showing >20% viable tumor cells.
- •ECOG PS 0,1
- •Age > 18 years
- •Patients must have normal organ and marrow function as defined below:
- •granulocytes >1,2500/mcL
- •platelets >100,000/mcL
- •total bilirubin < 1.5 x ULN, <1.8 x ULN with liver metastases
- •AST(SGOT)/ALT(SGPT) <2.5 X ULN without liver metastases; <5 X ULN with liver metastases
- •creatinine within normal institutional limits (<1.5) OR
- •creatinine clearance >50 mL/min/1.73m2, (for creatinine level above normal)
- •INR: < 1.5 (patients on warfarin need to be converted to LMWH during study participation to be eligible)
- •Consent to baseline metastatic and progressive disease biopsy (of metastatic/progressing lesion) for enabling biomarker assessment and treatment assignment (at each time point - baseline, PD1, PD2, PD3) as well as for correlative studies.
- •Consent to baseline and serial blood draws for plasma/serum/whole blood banking for correlative studies
- •Ability to understand and the willingness to sign a written informed consent document and consent to the serial nature of the proposed PANGEA treatment with first, second and third line therapy as tolerated.
- •Ability to comply with requirements of the protocol, as assessed by the investigator by the patient signing the consent form.
- •If history of exposure to anthracyclines during perioperative treatment, the following cumulative doses of anthracyclines must be less than:
- •Epirubicin < 720 mg/m2 Doxorubicin or liposomal doxorubicin < 360 mg/m2 Mitoxantrone > 120 mg/m2 and idarubicin > 90 mg/m2 If more than one anthracycline has been used, then the cumulative dose must not exceed the equivalent of 360 mg/m2 of doxorubicin.
- •Cardiac Ejection Fraction >50% (for HER2+ patients) as assessed by echocardiogram, MUGA scan, or cardiac MRI
- •Willingness to use effective and reliable methods of contraception (For appropriate methods of contraception considered acceptable see Appendix B).
- •Both men and women and members of all races and ethnic groups are eligible for this trial.
排除标准
- •No CVA within 6 months, no recent MI within 6 months
- •No currently active second malignancy
- •No uncontrolled intercurrent illness or infection
- •No peripheral edema > grade 2 at baseline.
- •No peripheral neuropathy > grade 2 at baseline.
- •No diarrhea > grade 2 at baseline.
研究组 & 干预措施
ITT-PTS: Personalized Treatment Strategy (Immuno-oncology)
For patients with monclonal antibiodies available, initial therapy was tailored based on biomarker profile as follows:
Immuno-oncology included PD-L1 IHC combined positivity score >10, high microsatellite instability, tumor mutation burden >15 mutations per megabase, and/or Epstein-Barr virus positive. These patients received standard cytotherapy plus Nivolumab.
干预措施: Nivolumab (Drug)
ITT-PTS: Personalized Treatment Strategy (Immuno-oncology)
For patients with monclonal antibiodies available, initial therapy was tailored based on biomarker profile as follows:
Immuno-oncology included PD-L1 IHC combined positivity score >10, high microsatellite instability, tumor mutation burden >15 mutations per megabase, and/or Epstein-Barr virus positive. These patients received standard cytotherapy plus Nivolumab.
干预措施: Standard cytotherapy (Drug)
ITT-PTS: Personalized Treatment Strategy (HER2 amplified)
HER2 amplified. These patients received standard cytotherapy plus Trastuzumab.
干预措施: Trastuzumab (Drug)
ITT-PTS: Personalized Treatment Strategy (HER2 amplified)
HER2 amplified. These patients received standard cytotherapy plus Trastuzumab.
干预措施: Standard cytotherapy (Drug)
ITT-PTS: Personalized Treatment Strategy (EFGR amplified)
EGFR amplified. These patients received ABT-806.
干预措施: ABT-806 (Drug)
ITT-PTS: Personalized Treatment Strategy (EFGR amplified)
EGFR amplified. These patients received ABT-806.
干预措施: Standard cytotherapy (Drug)
ITT-PTS: Personalized Treatment Strategy (FGFR2 amplified)
FGFR2 amplified. These patients received standard cytotherapy plus Bemarituzumab.
干预措施: Bemarituzumab (Drug)
ITT-PTS: Personalized Treatment Strategy (FGFR2 amplified)
FGFR2 amplified. These patients received standard cytotherapy plus Bemarituzumab.
干预措施: Standard cytotherapy (Drug)
ITT-PTS: Personalized Treatment Strategy (MAPK/PIK3CA aberrant)
MAPK/PIK3CA aberrant. These patients received standard cytotherapy plus Ramucirumab.
干预措施: Ramucirumab (Drug)
ITT-PTS: Personalized Treatment Strategy (MAPK/PIK3CA aberrant)
MAPK/PIK3CA aberrant. These patients received standard cytotherapy plus Ramucirumab.
干预措施: Standard cytotherapy (Drug)
ITT-PTS: Personalized Treatment Strategy (EGFR expressing)
EGFR expressing. These patients received standard cytotherapy plus ABT 806.
干预措施: ABT-806 (Drug)
ITT-PTS: Personalized Treatment Strategy (EGFR expressing)
EGFR expressing. These patients received standard cytotherapy plus ABT 806.
干预措施: Standard cytotherapy (Drug)
ITT-PTS: Personalized Treatment Strategy (All negative)
All negative. These patients received standard cytotherapy plus Ramucirumab.
干预措施: Ramucirumab (Drug)
ITT-PTS: Personalized Treatment Strategy (All negative)
All negative. These patients received standard cytotherapy plus Ramucirumab.
干预措施: Standard cytotherapy (Drug)
Non-ITT: Standard Therapy
Patients without monoclonal antibodies available received standard cytotherapy.
干预措施: Standard cytotherapy (Drug)
结局指标
主要结局
Overall Survival
时间窗: Up to 60 months
Time from enrollment to death from any cause.
次要结局
- Completion of Biopsy and Successful, Molecularly-based Treatment Assignment(Up to 1 month)
- Adverse Event From Serial Biopsy for Second-line Treatment(Up to 60 Months)
- Completion of Serial Biopsy for Second Line Therapy and Successful, Molecularly-based Treatment Assignment(Up to 60 months)
- Number of Biopsies Leading to an Adverse Event(1 Month)
- Adverse Event From Serial Biopsy for Third-line Treatment(Up to 60 months)
- Completion of Serial Biopsy for Third Line Therapy and Successful, Molecularly-based Treatment Assignment(Up to 60 months)