A RANDOMIZED, PHASE II STUDY COMPARING TRASTUZUMAB AND VINORELBINE IN COMBINATION WITH AVELUMAB OR AVELUMAB AND UTOMILUMAB (41BB/CD137 AGONIST), IN PATIENTS WITH HER2-POSITIVE METASTATIC BREAST CANCER WHO HAVE PROGRESSED ON PRIOR TRASTUZUMAB AND PERTUZUMAB: The "AVIATOR" Study
Are you eligible to participate in this study?
You may be eligible for this study if you meet the following criteria:
Conditions: HER2-positive metastatic breast cancer
Age: Between 18 - 100 Years
Gender: Male or Female
Age ≥18 years or older
Histologically confirmed breast cancer that is metastatic or unresectable loco-regionally advanced
Several other criteria will be evaluated by physician to determine eligibility.
1 Prior therapy with vinorelbine in any setting
2 Prior therapy with any anti-PD-1, anti-PD-L1, L2, anti-4-1BB (CD137), or anti-CTLA4 therapy
3Known Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
4Positive for Hepatitis B (HBsAg reactive) or Hepatitis C (HCV RNA [qualitative]).
5History of interstitial lung disease
6Active central nervous system metastases, as indicated by clinical symptoms, cerebral edema, and/or progressive growth (patients with history of CNS metastases or spinal cord compression are eligible if they are clinically stable for at least 4 weeks before first dose of investigational product and do not require high-dose steroid treatment)
7History of clinically significant or uncontrolled cardiac disease, including congestive heart failure (New York Heart Association functional classification > 3), angina, myocardial infarction or ventricular arrhythmia
8Previous severe hypersensitivity reaction to treatment with another monoclonal antibody
9Active infection requiring systemic therapy
10Chronic systemic therapy with immunosuppressive agents including corticosteroids
11Active autoimmune disease or a documented history of autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Patients with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Patients that require intermittent use of bronchodilators or local steroid injections would not be excluded from the trial. Patients with hypothyroidism stable on hormone replacement or Sjögren’s syndrome will not be excluded from the trial.
12Concurrent disease or condition that would make the patient inappropriate for trial participation or any serious medical disorder that would interfere with the patient’s safety in the opinion of the treating investigator.
13No current uncontrolled hypertension (≥180/110), unstable diabetes mellitus, dyspnea at rest, or chronic therapy with oxygen.
14Chemotherapy, radiotherapy, and/or biological cancer therapy within 3 weeks prior to the planned treatment start date
15Unresolved or unstable adverse events from prior therapy, except alopecia (has not recovered to CTCAE v.4 ≤grade 1 or baseline).
16Pregnant women or women who are lactating/breastfeeding due to the teratogenic potential of the study drugs
17Participants receiving any medications or substances that are strong inhibitors or inducers of CYP3A are ineligible. A list of medications and substances known or with the potential to interact with the CYP3A isoenzymes is provided in Appendix B. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list such as the Physicians’ Desk Reference. As part of the enrollment/informed consent procedures, the participant will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participant is considering a new over-the-counter medicine or herbal product.
18Live vaccines within 30 days prior to the first dose of trial therapy and during trial treatment.