A phase 2 study comparing MM-302 plus trastuzumab versus Chemotherapy of Physicians Choice plus trastuzumab in HER2+ metastatic breast cancer patients.

• Conditions: ocally Advanced/Metastatic HER2-Positive Breast Cancer; MedDRA version: 18.0Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-003159-73-ES
• Lead Sponsor: Merrimack Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-06-01
• Last Update Posted: 10 July 2015

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 250

Inclusion Criteria

Disease Specific Inclusion Criteria
1. Patients must have histologically or cytologically confirmed invasive cancer of the breast
2. Patients must have documented locally advanced/metastatic disease, defined by the investigator, which is not amenable to resection with curative intent
3. Patients must have HER2-positive breast cancer as defined by ASCO/CAP 2013 guidelines (Appendix 5) that is confirmed by a Sponsor-designated central laboratory
4. Patients must have archived tissue available to submit for analysis or be willing to undergo a biopsy for HER2 evaluation
5. Patients must be candidates for systemic chemotherapy
6. Patients must have documentation of disease progression (via RECIST or clinical progression) or intolerance during or after the most recent treatment for LABC/MBC
7. Patients must have progressed on, or be intolerant to treatment with these therapies:
a. pertuzumab in the LABC/MBC setting
b. ado-trastuzumab emtansine in the LABC/MBC setting
8. Patients must have been previously treated with trastuzumab in any setting (which may have been previously administered with or without pertuzumab)
General Inclusion Criteria
9. Patients must be >= 18 years of age
10. Patients or their legal representatives must be able to understand and sign an informed consent
11. Patients must have Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1
12. Patients must agree to abstain from sexual intercourse or to use a reliable form of contraception during the study and for 6 months following the last dose of assigned study drug(s). Exceptions: women who are no longer of childbearing potential
Hematologic, Biochemical and Organ Function
13. Patients must be eligible to receive at least one of the treatments constituting CPC according to the specific package insert or local practice guidelines for the given agent
14. Patients must have adequate bone marrow reserves as evidenced by:
a. Absolute neutrophil count (ANC) >= 1,500/µL
b. Platelet count >= 100,000/µL
c. Hemoglobin >= 9 g/dL (transfusions allowed)
15. Patients must have adequate coagulation function as evidenced by
a. International normalized ratio (INR) and activated partial thromboplastin time (aPTT) <=1.5 Upper Limit of Normal (ULN; unless on therapeutic coagulants)
16. Patients must have adequate hepatic function as evidenced by:
a. Serum total bilirubin within normal limits
b. Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) up to 3x upper limit of normal
c. Serum Albumin >= 2.5 g/dL
17. Patients must have adequate renal function as evidenced by a serum creatinine <= 1.5 x upper limit of normal
18. Patients must have adequate cardiac function as evidenced by a measured left ventricular ejection fraction of >= 50% by MUGA or ECHO. Measurements by ECHO must be read as a single value and not as a range
19. Patients must be recovered to at least CTCAE (v4.0) grade 1 from any clinically relevant toxic effects of any prior surgery, radiotherapy or other therapy intended for the treatment of breast cancer. For peripheral neuropathy, up to CTCAE (v4.0) Grade 2 is acceptable for patients with pre-existing condition. Patients with any grade of alopecia and/or fatigue may be enrolled.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 160
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 90

Exclusion Criteria

Disease Specific Exclusion Criteria:
1. Patients who have previously been treated with doxorubicin, liposomal doxorubicin, epirubicin, mitoxantrone or any other anthracycline derivative
2. Subjects with central nervous system (CNS) metastases, unless they have been treated and are stable without symptoms for 4 weeks after completion of treatment and they must be off steroids for at least 4 weeks prior to enrollment
3. Evidence of active malignancy or history of other malignancy within the last five years except for appropriately treated carcinoma of the cervix, non-melanoma skin carcinoma, stage 1 uterine cancer, or cancers with a similar curative outcome as those previously mentioned
4. Patients with known hypersensitivity to any of the components of MM 302 or who have had hypersensitivity reactions to fully humanized monoclonal antibodies
5. Patients with a history of intolerance to trastuzumab (i.e. a grade 3 or 4 infusion reaction) are excluded. Patients with a history of mild infusion reaction to trastuzumab who have previously been successfully re-challenged after an infusion reaction with or without prophylactic medication are allowed
6. Patients who have received other recent antitumor therapy prior to the first scheduled day of dosing with MM-302 defined as:
a. Investigational therapy administered within the 28 days (or 5 half-lives; whichever is the longest) prior to the first scheduled day of dosing
b. Any standard anti-cancer therapy within 14 days prior to the first scheduled day of dosing (excluding trastuzumab)
Cardiac Exclusion Criteria:
7. Patients with any class of NYHA congestive heart failure (CHF), heart failure with preserved ejection fraction (HFPEF)
8. Patients with a history of known coronary artery disease or a myocardial infarction within the last 12 months
9. Patients with hypertension (systolic BP > 150 mm Hg or diastolic BP > 100 mm Hg) that is not controlled by adequate standard anti-hypertensive treatment
10. Patients with known unstable angina pectoris
11. Patients with a known history of serious cardiac arrhythmias requiring treatment (exception: atrial fibrillation and paroxysmal supraventricular tachycardia)
12. Patients with a prolonged QTc interval (>= 450 ms)
13. Patients who previously discontinued trastuzumab due to unacceptable cardiac toxicity or infusion related reactions
14. Patients with a history of LVEF decline to below 50% during or after prior trastuzumab/lapatinib or other HER2 directed therapy
15. Patients with current dyspnea at rest due to complications of advanced malignancy or other disease that requires continuous oxygen therapy
General Exclusion Criteria:
16. Patients who are pregnant or breast feeding
17. Patients with an active infection or with an unexplained fever > 38.5°C during screening visits (at the discretion of the investigator, patients with tumor fever may be enrolled)
18. Patients with a history of allogeneic transplant (patients with a history of autologous bone marrow or stem cell transplant may be enrolled)
19. Patients with any other medical or social 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified