64-Cu Labeled Brain PET/MRI for MM-302 in Advanced HER2+ Cancers With Brain Mets
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Early Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. |
Drug: MM-302
Other Names:
Drug: Trastuzumab
Other Names:
|
Outcome Measures
Primary Outcome Measures
- MM-302 drug penetration into the brain [3 hours]
by Positron emission tomography-magnetic resonance (MR/PET) imaging
Secondary Outcome Measures
- Adverse event [1 year]
In overall cohort NCI CTCAE v.4.0
- Overall response rate [1 year]
By Revised Assessment in Neuro-Oncology (RANO) criteria
- Overall response rate [1 year]
By Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria
- Progession-free survival [1 year]
In the central nervous system (CNS)
- Progession-free survival [1 year]
Systemically
- CNS response rate [1 year]
In overall cohort
- Systemic response rate [1 year]
In overall cohort
- Adverse Event [1 year]
Treatment with radioactive MM-302
- Adverse Event [1 year]
Treatment with MM-302 and trastuzumab
Eligibility Criteria
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
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New or progressive brain metastases with at least one metastasis measuring ≥ 1 cm in longest diameter on MR imaging
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Patients may have extra-cranial metastatic disease but this is not required for study entry
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Neurologically stable as defined by ALL of the following:
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Stable or decreasing dose of steroids and anti-convulsants for at least 14 days prior to study entry
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No clinically significant mass effect, midline shift, or impending herniation on baseline brain imaging
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No significant focal neurologic signs and/or symptoms which would necessitate radiation therapy or surgical decompression in the judgment of the treating clinician
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Prior radiation therapy for treatment of brain metastases completed at least 4 weeks prior to study entry
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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
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Patients must be ambulatory with ECOG performance status of 0 - 1.
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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).
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Ejection fraction as assessed by MUGA or echocardiogram > 50%
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Prior cumulative doxorubicin exposure < 300 mg/m2 (or epirubicin equivalent)
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Last dose of prior systemic anti-cancer therapy administered at least 5 half-lives or 4 weeks prior to study entry, whichever is shorter
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No contra-indications to MRI (e.g. pacemaker, aneurysm clips, severe claustrophobia)
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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.
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Age ≥18 years old
Exclusion Criteria:
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Prior treatment with MM-302
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Patients with any class of New York Heart Association (NYHA) CHF or heart failure with preserved ejection fraction (HFPEF)
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Patients with a history of known coronary artery disease or a myocardial infarction within the last 12 months
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Patients with persistently uncontrolled hypertension (systolic BP > 160 mm Hg or diastolic BP > 100 mm Hg) despite optimal medical therapy
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Patients with known unstable angina pectoris
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Patients with a known history of serious cardiac arrhythmias requiring treatment (exception: controlled atrial fibrillation, paroxysmal supraventricular tachycardia)
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Patients with a prolonged QTc interval (≥ 450 ms)
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Patients who previously discontinued trastuzumab due to unacceptable cardiac toxicity
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Patients with a history of LVEF decline to below 50% during or after prior trastuzumab/lapatinib or other HER2 directed therapy.
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Current dyspnea at rest due to complications of advanced malignancy or other disease that requires continuous oxygen therapy.
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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
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Presence of leptomeningeal disease in the absence of parenchymal brain metastases
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Pamela Munster
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 15952