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

NCT02735798 | Withdrawn Early Phase 1 DMC

• 1 other identifier: 15952
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• MM-302 drug penetration into the brain

  by Positron emission tomography-magnetic resonance (MR/PET) imaging

  3 hours

Secondary Outcomes (9)

• Adverse event

  1 year

• Overall response rate

  1 year

• Overall response rate

  1 year

• Progession-free survival

  1 year

• Progession-free survival

  1 year

Study Arms (1)

Single Arm Study - Arm 1

EXPERIMENTAL

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; Drug: Trastuzumab

Interventions

MM-302 DRUG

Also known as: MM-302 brain study

Single Arm Study - Arm 1

Trastuzumab DRUG

Also known as: Herceptin

Single Arm Study - Arm 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Pamela Munster: lead

MeSH Terms

Conditions

Brain Neoplasms

Interventions

gancotamab; Trastuzumab

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 1, 2016
• First Posted: April 13, 2016
• Study Start: April 1, 2016
• Primary Completion: June 1, 2017
• Study Completion: June 1, 2018
• Last Updated: May 4, 2017

Record last verified: 2017-05