64-Cu Labeled Brain PET/MRI for MM-302 in Advanced HER2+ Cancers With Brain Mets

This is an interventional treatment trial for Brain Metastases Read More

Inclusion Criteria:

• 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 - 1.
• 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

Exclusion Criteria:

• 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