A Study of MM-111 and Paclitaxel with or without Trastuzumab in patients with Metastatic or Locally Advanced Cancer of the Esophagus, Gastroesophageal Junction and Stomach
- Conditions
- HER2 distal esophageal, Gastroesophageal (GE) junction or gastric carcinoma.MedDRA version: 16.1Level: PTClassification code 10017758Term: Gastric cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 16.1Level: LLTClassification code 10015362Term: Esophageal cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 16.1Level: LLTClassification code 10056267Term: Gastroesophageal cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2012-003798-25-GB
- Lead Sponsor
- Merrimack Pharmaceuticals Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 180
Patients will be qualified for study participation based on the following inclusion criteria:
- Patients must have documentation of histologically or cytologically confirmed metastatic or locally advanced adenocarcinoma of the distal esophagus, GE junction or stomach
- Patients must have documentation of histologically or cytologically confirmed HER2
expression as follows:
o Traditional HER2 Group 1: Patients who are HER2 3+ by IHC OR HER 2 2+ by IHC and HER2 gene amplified by FISH or CISH
o Non-Traditional HER2 Group 2: Patients who are HER2 2+ by IHC and HER2 gene nonamplified by FISH or CISH
- For Traditional HER2 Group 1
o Patients must have received one prior systemic therapy for metastatic disease, which must be a standard fluoropyrimidine/platinum-based frontline therapy given with or without trastuzumab
- Non-Traditional HER2 Group 2
o Patients must have received one prior systemic therapy for metastatic disease which must be a standard fluoropyrimidine/platinum-based frontline therapy given without trastuzumab
- Patients must be =18 years of age
- Patients or their legal representatives must be able to understand and sign an informed consent
- Patients should have evaluable or measurable disease =1 cm per RECIST 1.1
- Patients must have ECOG PS of 0, 1, or 2
- Patients must have adequate hematologic status as evidenced by:
o Absolute neutrophil count (ANC) =1500 cells/mm3
o Platelet count =100,000 platelets/mm3
o Hemoglobin =9 g/dL
- Patients must have adequate hepatic function as evidenced by:
o Serum total bilirubin =1.5 × the upper limit of normal (ULN)
o Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase =2.5 x ULN (5 × ULN is acceptable if liver metastases are present)
- Patients must have adequate renal function as evidenced by:
o Serum creatinine =1.5 × ULN or calculated clearance 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
- Patients must be recovered from the effects of any prior surgery, radiotherapy or other
antineoplastic therapy. NCI CTCAE v.4.0 up to grade 1 is acceptable for patients with preexisting peripheral neuropathy
- 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 6 months following the last dose of assigned study drug(s)
- Patients must have an archived formalin-fixed, paraffin-embedded (FFPE) tumor tissue
sample
- Patients must be willing and able to undergo a pre-treatment biopsy (this applies to the first
30 patients in each treatment group i.e. 30 for Traditional HER2 and 30 for Non-Traditional
HER2)
Are the trial subjects under 18? no
Number of subjects for this age range: 0
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 20
Patients will be disqualified from study participation based on the following exclusion criteria:
- Patients for whom potentially curative antineoplastic therapy is available
- Patients who previously received paclitaxel or other taxane treatment in the frontline or locally advanced setting
- Patients who are pregnant or lactating
- Patients with an active infection or with an unexplained fever >38.5°C during screening visits or on the first scheduled day of dosing (at the discretion of the investigator, patients
with tumor fever may be enrolled)
- Patients with known brain metastasis
- Patients with known hypersensitivity to any of the components of MM-111 or who have had
hypersensitivity reactions to fully human monoclonal antibodies
- Patients with a known history of hypersensitivity to paclitaxel or other drugs formulated in
Cremophor® EL, unless a patient has been de-sensitized in accordance with institutional
guidelines
- Patients with a known history of hypersensitivity to trastuzumab or any of its components
(for group 1 only)
- Patients who have received other recent anti-tumor therapy. This includes the following:
o Investigational therapy administered within the 28 days prior to the first scheduled day of dosing MM-111
- Dosing within <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
- Patients in the Traditional HER2 group already receiving trastuzumab do not require a wash-out period from trastuzumab (for group 1 only)
o Any standard chemotherapy or radiation or other therapy within 14 days prior to the
first scheduled dose of MM-111
o Patients who have not recovered from clinically significant effects of any prior surgery, radiotherapy or any other antineoplastic therapies. Patients with a known peripheral neuropathy must present with a grade 1 severity or less according to NCI CTCAE 4.0
Patients with active or prior history of New York Heart Association (NYHA) congestive heart failure or left ventricular ejection fraction (LVEF) <50%
- History of myocardial infarction within 12 months of enrollment
- Uncontrolled hypertension (systolic blood pressure >180 mm Hg or diastolic blood pressure
>100 mm Hg)
- Known angina pectoris requiring medication
- Known clinically significant heart valve disease
- Known history of high-risk arrhythmias requiring medical attention (chronic stable well controlled atrial fibrillation is permissible)
- Active gastrointestinal bleeding
- Patients who have received prior maximum cumulative anthracycline doses:
o Doxorubicin or liposomal doxorubicin doses >360 mg/m2
o Mitoxantrone >120 mg/m2 and idarubicin >90 mg/m2
o Epirubicin doses higher than 720 mg/m2
o Other (e.g., liposomal doxorubicin or other anthracycline equivalent of 360 mg/m2 of doxorubicin)
o If more than 1 anthracycline has been used, the cumulative dose must not exceed the equivalent of 360mg/m2 of doxorubicin
- Patients with known human immunodeficiency virus (HIV). Patients with Hepatitis B surface antigen (carriers) may be enrolled but must receive nucleoside/nucleotide analogue or other suitable treatment for Hepatitis B per institutional guidelines
- Patients with any other medical or psychological condition, deemed by the investigator to
likely interfere with a patient’s ability to sign informed consent or cooperate and participate
in the study, or interfere with the interpretation of the study results
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method