64-cu labeled brain pet/mri for mm-302 in advanced her2+ cancers with brain mets

Conditions: Brain Metastases; Documented Her2 Overexpression; Advanced Solid Tumor; Neurologically Stable

Summary: 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.


Eligibility criteria:
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