Clinical trial NCT01304797: Safety and Pharmacokinetic Study of MM-302 in Patients With Advanced Breast Cancer
Official title: A Phase 1, Multi-Center, Open-Label, Dose-Escalation, Safety, and Pharmacokinetic Clinical Study of Intravenously Administered MM-302 Monotherapy and in Combination With Trastuzumab With or Without Cyclophosphamide in Patients With Advanced HER2 Positive Breast Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Breast Cancer
Keywords: MM302
Breast Cancer
Locally advanced/unresectable
metastatic
Lead sponsor: Merrimack Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2011-02-25
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is a Phase 1 and pharmacologic open-label dose-escalation trial using a "3+3" design. Successive cohorts of three or more patients will be treated at escalating doses until a maximum tolerated dose is identified. Once the maximum tolerated dose is identified, an Expansion Cohort will be enrolled at that dose to further characterize safety and pharmacologic endpoints. Additional arms will be enrolled to explore the combination of MM-302 with trastuzumab or trastuzumab plus cyclophosphamide in patients with advanced HER2 positive breast cancer.


Eligibility criteria: Inclusion Criteria:

* Locally advanced/unresectable or metastatic breast cancer
* Eighteen years of age or above
* Able to understand and sign an informed consent (or have a legal representative who is able to do so)
* Measurable disease according to RECIST v1.1
* ECOG Performance Score of 0 or 1
* Adequate bone marrow, hepatic, renal and cardiac function
* Willing to abstain from sexual intercourse or to use an effective form of contraception during the study and for 90 days following the last dose of MM-302

Exclusion Criteria:

* Patients for whom potentially curative anticancer therapy is available
* Active infection or fever \> 38.5°C during screening visits or on the first scheduled day of dosing
* Symptomatic CNS disease
* Known hypersensitivity to any of the components of MM-302 or who have had hypersensitivity reactions to fully human monoclonal antibodies
* Received other recent antitumor therapy
* Pregnant or breast feeding
* Patients with any other medical or psychological condition, deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results

Primary outcomes:
measure: The severity and the number of adverse events related to escalating doses of the MM-302.
timeFrame: 12 months
measure: The severity and the number of adverse events related to escalating doses of the MM-302 in combination with trastuzumab with or without cyclophosphamide
timeFrame: 12 months
Secondary outcomes:
measure: Objective response rate of MM-302
timeFrame: 12 months
measure: The pharmacokinetics of MM-302 as determined by measuring AUC, Tmax and Cmax
timeFrame: 12 months
measure: Immunogenicity of MM-302 by confirming whether MM-302 elicits an immune response or not
timeFrame: 12 months
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Indianapolis
country: United States
facility: University of Indiana
state: Indiana
city: Boston
country: United States
facility: Dana Farber Cancer Center
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Center
state: Michigan
city: St. Louis
country: United States
facility: Washington University
state: Missouri
Study officials:
References:
citation: Lee H, Shields AF, Siegel BA, Miller KD, Krop I, Ma CX, LoRusso PM, Munster PN, Campbell K, Gaddy DF, Leonard SC, Geretti E, Blocker SJ, Kirpotin DB, Moyo V, Wickham TJ, Hendriks BS. 64Cu-MM-302 Positron Emission Tomography Quantifies Variability of Enhanced Permeability and Retention of Nanoparticles in Relation to Treatment Response in Patients with Metastatic Breast Cancer. Clin Cancer Res. 2017 Aug 1;23(15):4190-4202. doi: 10.1158/1078-0432.CCR-16-3193. Epub 2017 Mar 15.