Clinical trial NCT01097460: MM-111 in Combination With Herceptin in Patients With Advanced Her2 Amplified, Heregulin Positive Breast Cancer
Official title: MM-111-02-12-02: A Phase 1 Study of MM-111 in Combination With Herceptin in Patients With Advanced, Refractory Her2 Amplified, Heregulin Positive Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Breast Neoplasms
Keywords: HER2/HER3
Bispecific Antibody
Breast Cancer
Advanced Breast Cancer
Metastatic Breast Cancer
HER2 Positive Breast Cancer
Trastuzumab
Herceptin
Lead sponsor: Merrimack Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2010-04-01
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open-label Phase 1 trial of MM-111 in combination with Herceptin.

Detailed description: Phase 1: Safety and tolerability of the MM-111 + Herceptin combination will be evaluated and the recommended Phase 2 dose will be determined.

Eligibility criteria: Inclusion Criteria:

* Patients must have histologically or cytologically confirmed advanced breast cancer that is amplified for HER2, based on archived tumor biopsy (IHC 2+ or greater)
* Patients must have histologically or cytologically confirmed advanced breast cancer that is heregulin positive based on fresh tumor tissue biopsy
* The patient's cancer must have recurred, progressed or not responded to standard chemotherapy or other standard treatment. Prior therapies may include but are not limited to Herceptin, Tykerb (lapatinib), anthracyclines, and taxanes
* Patients must be ≥ 18 years of age
* Patients or their legal representatives must be able to understand and sign an informed consent
* Patients may have measurable (per RECIST 1.1) or non-measurable tumor(s) (for Phase 1)
* Patients should have ECOG Performance Score (PS) 0, 1 or 2 (for Phase 1).
* Patients should have a life expectancy of at least 12 weeks
* Patients must have adequate bone marrow reserves
* Patients must have adequate hepatic function
* Patients must have adequate renal function
* Patients must be recovered from the effects of any prior surgery, radiotherapy or other antineoplastic therapy.
* Women of childbearing potential as well as fertile men and their partners must agree 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-111.

Exclusion Criteria:

* Patients who are pregnant or lactating
* Patients with an active infection or with an unexplained fever \> 38.5°C (101.3° F) during screening visits or on the first scheduled day of dosing.
* Patients with untreated and/or symptomatic metastatic CNS malignancies.
* Patients with known hypersensitivity to any of the components of MM-111 or who have had hypersensitivity reactions to fully human monoclonal antibodies, including Herceptin.
* Patients who have received other recent antitumor therapy including:

  * Treatment with Herceptin within the 28 days prior to the first scheduled day of dosing with MM-111
  * Investigational therapy administered within the 28 days prior to the first scheduled day of dosing MM-111 (Dosing in less than 28 days' since receiving investigational therapy is acceptable once a time interval equal to at least five half-lives of the investigational agent has passed.)
  * Any standard chemotherapy, Tykerb (lapatinib) or radiation within 14 days (and having passed the time of any actual or anticipated toxicities) prior to the first scheduled dose of MM-111
* Patients who have previously received MM-111
* Patients with NYHA Class III or IV congestive heart failure or LVEF \< 50%
* Patients with a history of allogeneic transplant
* Patients with known HIV, hepatitis B or C (if patients have previously been treated for hepatitis C and have undetectable viral loads, they can be considered eligible for the trial)
* 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: Incidence of Treatment-emergent AE's
timeFrame: 2 years
Secondary outcomes:
measure: To Determine the Recommended Phase 2 Doses of MM-111 + Herceptin in Combination
timeFrame: 2 years
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana University (IUPUI)
state: Indiana
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
Study officials:
affiliation: Massachusetts General Hospital
name: Michaela Higgins, MD
role: PRINCIPAL_INVESTIGATOR
References: