Clinical Trials /

Tolerability of the Combination of Lapatinib and Trastuzumab in Adults Age 60 or Older With HER2 Positive Locally Advanced or Metastatic Breast Cancer

NCT01273610

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Tolerability of the Combination of Lapatinib and Trastuzumab in Adults Age 60 or Older With HER2 Positive Locally Advanced or Metastatic Breast Cancer
  • Official Title: Tolerability of the Combination of Lapatinib and Trastuzumab in Adults Age 60 or Older With HER2 Positive Locally Advanced or Metastatic Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: 10112
  • SECONDARY ID: NCI-2011-00116
  • NCT ID: NCT01273610

Conditions

  • Breast Neoplasms
  • HER2/Neu Positive
  • Geriatric Health Services

Interventions

DrugSynonymsArms
LapatinibTykerb, Tyverb, GSK572016, GW-572016, GW2016Lapatinib and trastuzumab
TrastuzumabHerceptinLapatinib and trastuzumab

Purpose

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.

Detailed Description

      PRIMARY OBJECTIVES: I. To estimate the safety and tolerability of the combination of
      trastuzumab and lapatinib (lapatinib ditosylate) in adults age 60 or older with locally
      advanced or metastatic breast cancer. SECONDARY OBJECTIVES: I. To describe the full toxicity
      profile including all grades; to estimate the rate of all grades of cardiac toxicity; to
      estimate the rate of all grades of diarrhea, nausea, and vomiting. II. To describe the
      pharmacokinetic parameters of lapatinib in older adults. III. To estimate objective response
      rate and clinical benefit rate as defined by modified Response Evaluation Criteria In Solid
      Tumors (RECIST) criteria. IV. To estimate median progression-free and overall survival. V. To
      explore factors other than chronological age that can affect toxicity rates as identified
      using a cancer-specific geriatric assessment. VI. To estimate rates of adherence to lapatinib
      in older adults.

      OUTLINE: Patients receive lapatinib ditosylate orally (PO) once daily (QD) and trastuzumab
      intravenously (IV) over 30-90 minutes once weekly OR once every 3 weeks. Courses repeat every
      21 days in the absence of disease progression or unacceptable toxicity. After completion of
      study treatment, patients are followed up for 30 days and then periodically thereafter.
    

Trial Arms

NameTypeDescriptionInterventions
Lapatinib and trastuzumabExperimentalPatients receive lapatinib ditosylate PO QD and trastuzumab IV once weekly OR once every 3 weeks. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
  • Lapatinib
  • Trastuzumab

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:60 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Grade 3 or higher non-hematological toxicities and symptomatic congestive heart failure (as defined by NCI CTCAE v.4.0)
Time Frame:Until 30 days after last dose of treatment
Safety Issue:
Description:Tables will be created to summarize the toxicities and side effects for each dose schedule by dose, course, organ and severity for all patients. All serious adverse events and other serious toxicities will be described on a patient by patient basis. Numbers of cycles received and dose reductions will be tabulated by dose. Rates and associated 95% exact Clopper and Pearson binomial confidence intervals will be estimated.

Secondary Outcome Measures

Measure:All toxicities associated with the combinations as measured by NCI CTCAE v. 4.0
Time Frame:Until 30 days after last dose of treatment
Safety Issue:
Description:Rates and associated 95% exact Clopper and Pearson binomial confidence intervals will be estimated.
Measure:Dose reductions, dose interruptions, dose discontinuations
Time Frame:While on treatment
Safety Issue:
Description:Rates and associated 95% exact Clopper and Pearson binomial confidence intervals will be estimated.
Measure:Tumor response (using RECIST criteria)
Time Frame:Up to 8 years
Safety Issue:
Description:Response rate (complete response [CR] + partial response [PR]) and clinical benefit rate (CR + PR + stable disease [SD]) and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated.
Measure:Progression-free survival
Time Frame:From start of treatment until documented disease progression or death
Safety Issue:
Description:
Measure:Overall survival
Time Frame:From start of treatment until death from any cause
Safety Issue:
Description:
Measure:Pharmacokinetic parameters of lapatinib, including trough levels and area under curve (AUC)
Time Frame:Day 15 of course 1 and days 1 and 8 of course 2
Safety Issue:
Description:AUC will be calculated and reported using standard descriptive statistics.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:City of Hope Medical Center

Trial Keywords

  • Breast Neoplasms
  • HER2 protein, human
  • Geriatric Health Services
  • Antineoplastic Agents, Combined
  • Geriatric Assessment
  • Pharmacokinetics
  • Toxicity
  • Patient Adherence

Last Updated

August 18, 2017