A Pilot Study of 64-Cu Labeled Brain PET/MRI for MM-302, a Novel HER2 Targeting Agent, in Advanced HER2+ Cancer With Brain Metastases
试验速览
- 阶段
- 早期 1 期
- 状态
- 撤回
- 主要终点
- MM-302 drug penetration into the brain
研究概览
简要总结
This is a single arm pilot study of 64Cu-MM-302 and unlabeled MM-302 in combination with trastuzumab in 10 patients with advanced HER2+ cancer with new or progressive brain metastases. Patients will receive standard imaging at baseline, including FDG-PET/CT plus MR brain imaging. Patients will subsequently start protocol therapy with MM-302 and trastuzumab given on day 1 of an every 21-day dosing cycle, at the recommended phase 2 dose of 30 mg/m2. Patients will receive 64Cu-labeled MM-302 (3-5 mg/m2 doxorubicin) three hours after unlabeled dose of MM-302. Integrated MR/PET imaging of the brain and whole body will be performed at two time points following 64Cu-labeled MM-302 administration: (1) within 3 hours (+/- 1 hour) of labeled drug injection, and (2) 24 hours (+/- 6 hours) post-injection. Patients will continue to receive subsequent doses of unlabeled MM-302 plus trastuzumab every 3 weeks until clinical or radiographic disease progression (either in the brain or systemically) or unacceptable toxicity, whichever occurs soonest. MR brain imaging and FDG-PET/CT scans will be performed every 9 weeks to monitor for treatment response and disease progression.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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 advanced solid tumor malignancy with documented HER2 overexpression or gene amplification on prior archival tumor tissue by CLIA-certified laboratory
- •New or progressive brain metastases with at least one metastasis measuring ≥ 1 cm in longest diameter on MR imaging
- •Patients may have extra-cranial metastatic disease but this is not required for study entry
- •Neurologically stable as defined by ALL of the following:
- •Stable or decreasing dose of steroids and anti-convulsants for at least 14 days prior to study entry
- •No clinically significant mass effect, midline shift, or impending herniation on baseline brain imaging
- •No significant focal neurologic signs and/or symptoms which would necessitate radiation therapy or surgical decompression in the judgment of the treating clinician
- •Prior radiation therapy for treatment of brain metastases completed at least 4 weeks prior to study entry
- •Prior radiation therapy for brain metastases allowed but must have been at least 4 weeks prior to study entry and follow up imaging is not consistent with pseudoprogression in the judgment of treating clinician
- •Patients must be ambulatory with ECOG performance status of 0 -
- •Adequate organ function, including absolute neutrophil count (ANC) ≥1500 cells/uL, hemoglobin ≥9.0 gm/dL, platelets ≥100,000 cells/uL, estimated creatinine clearance ≥50 mL/min (by the Cockcroft Gault equation), bilirubin <1.5x ULN (unless Gilbert's is suspected), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <1.5x ULN (< 3x ULN if known liver metastases).
- •Ejection fraction as assessed by MUGA or echocardiogram > 50%
- •Prior cumulative doxorubicin exposure < 300 mg/m2 (or epirubicin equivalent)
- •Last dose of prior systemic anti-cancer therapy administered at least 5 half-lives or 4 weeks prior to study entry, whichever is shorter
- •No contra-indications to MRI (e.g. pacemaker, aneurysm clips, severe claustrophobia)
- •Patients will sign a study-specific IRB-approved consent prior to study entry. Patients must be able and willing to consent and undergo study procedures.
- •Age ≥18 years old
排除标准
- •Prior treatment with MM-302
- •Patients with any class of New York Heart Association (NYHA) CHF or heart failure with preserved ejection fraction (HFPEF)
- •Patients with a history of known coronary artery disease or a myocardial infarction within the last 12 months
- •Patients with persistently uncontrolled hypertension (systolic BP > 160 mm Hg or diastolic BP > 100 mm Hg) despite optimal medical therapy
- •Patients with known unstable angina pectoris
- •Patients with a known history of serious cardiac arrhythmias requiring treatment (exception: controlled atrial fibrillation, paroxysmal supraventricular tachycardia)
- •Patients with a prolonged QTc interval (≥ 450 ms)
- •Patients who previously discontinued trastuzumab due to unacceptable cardiac toxicity
- •Patients with a history of LVEF decline to below 50% during or after prior trastuzumab/lapatinib or other HER2 directed therapy.
- •Current dyspnea at rest due to complications of advanced malignancy or other disease that requires continuous oxygen therapy.
- •Any serious and/or unstable pre-existing medical, psychiatric, or other medical condition that could interfere with subject's safety, provision of informed consent, or compliance with study procedures
- •Presence of leptomeningeal disease in the absence of parenchymal brain metastases
研究组 & 干预措施
Single Arm Study - Arm 1
10 patients will receive standard imaging at baseline, incl. FDG-PET/CT plus MR brain imaging. Patients will subsequently start protocol therapy with MM-302 and trastuzumab given on day 1 of an every 21-day dosing cycle, at recommended phase 2 dose of 30 mg/m2. Patients will receive 64Cu-labeled MM-302 (3-5 mg/m2 doxorubicin) 3 hours after unlabeled dose of MM-302. Integrated MR/PET imaging of brain and whole body will be performed at 2 time points following 64Cu-labeled MM-302 administration: (1) within 3 hours (+/- 1 hour) of labeled drug injection, and (2) 24 hours (+/- 6 hours) post-injection. Patients will continue to receive doses of unlabeled MM-302 plus trastuzumab every 3 weeks until clinical or radiographic disease progression (in brain or systemically) or unacceptable toxicity, whichever occurs soonest. MRI and FDG-PET/CT scans will be performed every 9 weeks to monitor for treatment response and disease progression.
干预措施: MM-302 (Drug)
Single Arm Study - Arm 1
10 patients will receive standard imaging at baseline, incl. FDG-PET/CT plus MR brain imaging. Patients will subsequently start protocol therapy with MM-302 and trastuzumab given on day 1 of an every 21-day dosing cycle, at recommended phase 2 dose of 30 mg/m2. Patients will receive 64Cu-labeled MM-302 (3-5 mg/m2 doxorubicin) 3 hours after unlabeled dose of MM-302. Integrated MR/PET imaging of brain and whole body will be performed at 2 time points following 64Cu-labeled MM-302 administration: (1) within 3 hours (+/- 1 hour) of labeled drug injection, and (2) 24 hours (+/- 6 hours) post-injection. Patients will continue to receive doses of unlabeled MM-302 plus trastuzumab every 3 weeks until clinical or radiographic disease progression (in brain or systemically) or unacceptable toxicity, whichever occurs soonest. MRI and FDG-PET/CT scans will be performed every 9 weeks to monitor for treatment response and disease progression.
干预措施: Trastuzumab (Drug)
结局指标
主要结局
MM-302 drug penetration into the brain
时间窗: 3 hours
by Positron emission tomography-magnetic resonance (MR/PET) imaging
次要结局
- Adverse event(1 year)
- Overall response rate(1 year)
- Progession-free survival(1 year)
- CNS response rate(1 year)
- Systemic response rate(1 year)
- Adverse Event(1 year)
研究者
Pamela Munster
Professor
University of California, San Francisco