Tolerability of the Combination of Lapatinib and Trastuzumab in Adults Age 60 or Older With HER2 Positive Locally Advanced or Metastatic Breast Cancer
Condition: Breast Neoplasms; HER2/Neu Positive; Geriatric Health Services
MeSH terms: Breast Neoplasms
Intervention: Lapatinib; Trastuzumab; laboratory biomarker analysis; pharmacological study
Intervention description: 250 mg tablets; Intravenous injection
Intervention MeSH terms: Trastuzumab; Lapatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 40.0
Sex: All
Minimum age: 60 Years
Healthy volunteers: No
Keywords: Breast Neoplasms; HER2 protein, human; Geriatric Health Services; Antineoplastic Agents, Combined; Geriatric Assessment; Pharmacokinetics; Toxicity; Patient Adherence

Summary:

      This phase II trial studies the side effects and how well lapatinib ditosylate and
      trastuzumab work in treating older patients with human epidermal growth factor receptor 2
      (HER2)-positive breast cancer that has spread from where it started to nearby tissue or lymph
      nodes (locally advanced) or to other parts of the body (metastatic). Lapatinib ditosylate may
      stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
      Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some
      block the ability of tumor to grow and spread. Others find tumor cells and help kill them or
      tumor cancer-killing substances to them. Giving lapatinib ditosylate together with
      trastuzumab may kill more tumor cells.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Locally advanced or metastatic Her2/Neu positive breast cancer (defined as
             immunohistochemistry [IHC] 3+ or a fluorescence in situ hybridization [FISH] ratio of
             >= 2.0); this may be on either a primary tumor or a metastatic site, and there is no
             time limit from the time the specimen was obtained; locally advanced breast cancer
             (LABC) includes breast cancers with advanced primary tumors, i.e., large diameter (at
             least 5 cm) or those with skin and/or chest wall involvement, and advanced regional
             lymph node involvement; it also includes a rare subgroup, inflammatory breast cancer;
             in the 2010 American Joint Committee on Cancer and the International Union for Cancer
             Control (AJCC-UICC) TNM breast cancer staging system, locally advanced breast cancer
             (LABC) includes patients with stage III disease; this comprises:

               -  Advanced primary tumors (tumors > 5 cm in greatest dimension [T3]; direct
                  extension to the chest wall and/or to the skin [T4]: ulceration, skin nodules,
                  and/or edema (including peau d'orange) confined to the same breast, inflammatory
                  breast cancer [IBC, T4d])

               -  Advanced regional lymph nodes (ipsilateral level I, II axillary lymph nodes that
                  are clinically fixed or matted or clinically detected internal mammary lymph
                  nodes in the absence of axillary lymph node metastases [N2], ipsilateral
                  infraclavicular [level III axillary] lymph nodes, ipsilateral internal mammary
                  lymph node[s] with axillary lymph nodes, or ipsilateral supraclavicular lymph
                  nodes [N3])

          -  Both measurable and non-measurable disease are allowed

          -  Life expectancy of greater than 12 weeks

          -  Women of child-bearing potential and sexually active men must agree to use adequate
             contraception prior to study entry for six months following duration of study
             participation

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky
             performance status >= 60%)

          -  Hemoglobin >= 10 g/dL (after transfusion if necessary)

          -  Absolute neutrophil count >= 1,500/mcL

          -  Platelets >= 100,000/mcL

          -  Total bilirubin within normal institutional limits

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/aspartate aminotransferase (ALT) (serum glutamate pyruvate transaminase
             [SGPT]) =< 2.5 X institutional upper limit of normal

          -  Creatinine clearance >= 30 mL/min as measured using either the Cockcroft-Gault method
             or 24-hour creatinine clearance

          -  The above tests must be obtained within 14 days of study treatment

          -  Cardiac ejection fraction >= 50% as measured by echocardiogram or multiple gated
             acquisition scan (MUGA) scan

          -  The ability to swallow and retain oral medication

          -  Prior treatment with lapatinib or trastuzumab are allowed, provided that the agents
             have never been given in combination

          -  Any number of prior cancer treatments, including investigational agents, chemotherapy,
             hormone therapy, or targeted therapy are allowed

          -  All patients must have the ability to understand and the willingness to sign a written
             informed consent

        Exclusion Criteria:

          -  Concurrent investigational treatment, chemotherapy, or targeted therapy; prior
             chemotherapy, hormonal therapy, targeted therapy, and investigational agents are
             allowed but all toxicities grade >= 2 must have resolved by the time of study
             commencement (except alopecia)

          -  Unstable or symptomatic brain metastases (however, patients with stable or treated
             brain metastases who do not require steroids at doses above those permitted for
             control of symptoms may be enrolled)

          -  History of allergic reactions attributed to compounds of similar chemical or
             biological composition to lapatinib or trastuzumab; however, patients with a history
             of infusion reaction to trastuzumab which was controlled with premedication on
             subsequent infusions without a recurring infusion reaction are eligible

          -  Concomitant medications listed are prohibited; inhibitors or inducers of cytochrome
             P450 3A4 (CYP3A4) not listed can be used with caution

          -  Ongoing or active infection (including human immunodeficiency virus [HIV]) or
             psychiatric illness/social situations that would limit compliance with study
             requirements

          -  Inability to take oral medication

          -  Malabsorption syndrome, (prior surgical procedures affecting absorption), or
             inflammatory gastrointestinal (GI) disease (e.g., Crohn's, ulcerative colitis) which
             in the opinion of the study coordinator is likely to limit normal absorption of the
             drug

          -  Current active hepatic or biliary disease (with the exception of patients with
             Gilbert's syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver
             disease per investigator assessment)

          -  Active cardiac disease, defined as (but not limited to):

               -  History of documented congestive heart failure (CHF) or systolic dysfunction
                  (left ventricular ejection fraction [LVEF] < 50%)

               -  High-risk uncontrolled arrhythmias (ventricular tachycardia, high-grade
                  atrio-ventricular [AV]-block, supraventricular tachycardias which are not
                  adequately rate-controlled)

               -  Angina pectoris requiring antianginal medications

               -  Evidence of transmural infarction on electrocardiogram (ECG)

               -  Clinically significant valvular heart disease

               -  Poorly controlled hypertension (e.g. systolic > 180 mm HG or diastolic > 100 mm
                  Hg)

               -  Any other cardiac condition, which in the opinion of the treating physician would
                  make this protocol unreasonably hazardous for the patient

          -  Subjects who, in the opinion of the investigator, may not be able to comply with the
             safety monitoring requirements of the study are not eligible