Triple Negative Breast Cancer (advanced breast cancer that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective) MedDRA version: 16.0 Level: LLT Classification code 10072737 Term: Advanced breast cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: MK-8109
Product Code: MK-8109
Pharmaceutical Form: Powder for solution for injection
CAS Number: 74209-03-1
Current Sponso
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Female subjects must have histologically or cytologically confirmed ER-, PR-, HER2 – advanced breast cancer that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective - Have developed progressive disease following at least 1 (and not more than 4) prior chemotherapeutic regimens for breast cancer, which was administered for treatment of locally recurrent and/or metastatic disease - At least 1 regimen must have included a taxane (e.g. paclitaxel or docetaxel) in any combination or order. Prior taxane may have been administered as adjuvant and/or neoadjuvant therapy. - Subject is = 18 years of age on day of signing informed consent - Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 - Have at least a single (RECIST 1.1 defined) measurable lesion - All tumor target lesions characterized as FR(100%) using etarfolatide screened assessed by central core facility. 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 68 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 34
Exclusion criteria
Exclusion criteria: Has had chemotherapy, radiotherapy, or biological therapy (including monoclonal antibodies) within 4 weeks prior to drug administration or who has not recovered (=Grade 1 or baseline) from adverse events due to agents administered more than 4 weeks earlier. - Is currently participating or has participated in a study with an investigational compound or device within 28 days of initial dosing on this study. - Has received more than 4 prior cytotoxic regimens for metastatic disease. - Has a primary central nervous system (CNS) tumor. - Has active CNS metastases and/or carcinomatous meningitis. However, subjects with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for 1 month prior to entry as defined as: (1) no evidence of new or enlarging CNS metastasis (2) off steroids or on a stable dose of steroids for at least 2 weeks. - Has had prior therapy with vinorelbine (Navelbine®) or vinca-containing compounds. - Has known hypersensitivity to the components of the study therapy or its analogs. This includes paclitaxel, docetaxel, other taxane therapies, drugs formulated with polyoxyethylated castor oil (Cremphor EL), vinlastine, or other vinca-derived therapies. - Has pre-existing neuropathy > Grade 2. Subjects with residual drug-induced neuropathy of =2 will be eligible if it has stable, and not worsening, for at least 30 days. - Has a bowel occlusion or subocclusion. - Has had prior abdominal or pelvis radiation therapy or radiation therapy to > 10% of the bone marrow at any time in the past or prior radiation therapy within the last three years to the breast/sternum, dermal lesions, head, or neck. - Requires anti-folate therapy for the management of co-morbid conditions (e.g., rheumatoid arthritis). - Has symptomatic ascites or pleural effusion. A subject who is clinically stable following treatment for these conditions is eligible for the study however. - Has had a prior stem cell or bone marrow transplant
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the progression-free survival of vintafolide monotherapy relative to paclitaxel and the progression-free survival of vintafolide + paclitaxel combination therapy relative to paclitaxel in subjects with advanced triple negative breast cancer whose target lesions are 100% positive for folate receptor expression using etarfolatide scans.; Secondary Objective: 1. To assess the frequency of triple negative breast cancer subjects whose target tumors express FR(100%) versus FR(10-90%) versus FR(0%) using etarfolatide scans. 2. To determine the correlation between FOLR1 mRNA expression in tumors in subjects with advanced triple negative breast cancer and subject etarfolatide target lesion scores (FR[100%], FR[10-90%], FR[0%]) measured by etarfolatide. 3. To compare the clinical activity of vintafolide monotherapy versus paclitaxel and the clinical activity of vintafolide + paclitaxel combination therapy versus paclitaxel in subjects with advanced triple negative breast cancer as measured by Overall Response Rate, Clinical Benefit Rate, and Overall Survival. 4. To assess the safety and tolerability of vintafolide monotherapy versus the combination of vintafolide and paclitaxel versus paclitaxel monotherapy in subjects with advanced triple negative breast cancer. ;Primary end point(s): The primary analysis will be to evaluate PFS which is generally accepted as an endpoint (or the closely related time to progression [TTP] endpoint) for clinical trials in patients with breast cancer. ;Timepoint(s) of evaluation of this end point: PFS will be assessed throughout the study and measured as the time from randomization to the time of disease progression or death. Patients will receive imaging assessments at 8 week intervals throughout the study to assess response. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Overall Response Rate (ORR): Disease response will be assessed throughout the study by anatomic imaging evaluation and physical exam of visible/palpable tumor. Overall tumor response will be assessed using Enhanced RECIST 1.1 at the designated time points. The portion of patients with tumor size reduction predefined by RECIST 1.1, including patients with complete response (CR) and partial response (PR), will be evaluated. 2. Clinical Benefit Rate (CBR): Disease control rates (DCR), which include stable disase (SD) as a response measure offer additional advantages over ORRs, since they are also associated with overall survival (OS) in breast cancer. During clinical development of Eribulin, SD lasting > 6 months was used to assess CBR as CR + PR + SD (=6 months). Since the same criteria were used to assess vintafolide activity in initial monotherapy trials in ovarian cancer, the CBR for this trial will be defined as CR + PR + SD (=6 months). 3.Overall Survival (OS): OS data defined as the time from randomization until death from any cause will be collected as a universally accepted direct measure of benefit. 4. Safety: The study will use standard endpoints that allow one to see results in context for comparison with large historical databases. Safety and tolerability of vintafolide in multiple indications will be assessed in advanced cancer subjects. Monitoring will include complete blood counts, serum chemistry, vital signs, physical exam, ECGs, and ECOG performance status. 5. Pharmackokinetic Endpoints: For the initial dose of vintafolide and paclitaxel for each subject, plasma concentration-time profiles will be determined following IV administration. The following PK parameters will be determined for vintafolide and paclitaxel: maximum observed plasma concentration (Cmax); area under the plasma concentration-time curve (AUC); and if feasible, half-life (t1/2); total | — |
Countries
Denmark, Spain, Sweden
Contacts
Public ContactGlobal Clinical Trials Operations
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Outcome results
None listed