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

Advanced Solid Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02735798
• Other study ID #: 15952
• Status: Withdrawn
• Phase: Early Phase 1
• First received: April 1, 2016
• Last updated: May 2, 2017
• Start date: April 2016
• Est. completion date: June 2018

Study information

• Verified date: May 2017
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: June 2018
• Est. primary completion date: June 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Brain Metastases
• Brain Neoplasms
• Documented Her2 Overexpression
• Neoplasm Metastasis
• Neurologically Stable

Intervention

Drug:
• MM-302

• Trastuzumab

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Pamela Munster

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MM-302 drug penetration into the brain	by Positron emission tomography-magnetic resonance (MR/PET) imaging	3 hours
Secondary	Adverse event	In overall cohort NCI CTCAE v.4.0	1 year
Secondary	Overall response rate	By Revised Assessment in Neuro-Oncology (RANO) criteria	1 year
Secondary	Overall response rate	By Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria	1 year
Secondary	Progession-free survival	In the central nervous system (CNS)	1 year
Secondary	Progession-free survival	Systemically	1 year
Secondary	CNS response rate	In overall cohort	1 year
Secondary	Systemic response rate	In overall cohort	1 year
Secondary	Adverse Event	Treatment with radioactive MM-302	1 year
Secondary	Adverse Event	Treatment with MM-302 and trastuzumab	1 year