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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2015 by City of Hope Medical Center
Sponsor:
Collaborators:
GlaxoSmithKline
Genentech, Inc.
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT01273610
First received: January 6, 2011
Last updated: April 7, 2015
Last verified: April 2015

January 6, 2011
April 7, 2015
April 2011
March 2019   (final data collection date for primary outcome 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 ] [ Designated as safety issue: Yes ]
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.
Grade 3 or higher toxicities (as defined by NCI CTCAE v.4.0) [ Time Frame: Until 30 days after last dose of treatment ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01273610 on ClinicalTrials.gov Archive Site
  • All toxicities associated with the combinations as measured by NCI CTCAE v. 4.0 [ Time Frame: Until 30 days after last dose of treatment ] [ Designated as safety issue: Yes ]
    Rates and associated 95% exact Clopper and Pearson binomial confidence intervals will be estimated.
  • Dose reductions, dose interruptions, dose discontinuations [ Time Frame: While on treatment ] [ Designated as safety issue: Yes ]
    Rates and associated 95% exact Clopper and Pearson binomial confidence intervals will be estimated.
  • Tumor response (using RECIST criteria) [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]
    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.
  • Progression-free survival [ Time Frame: From enrollment until documented disease progression or death ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: From enrollment until death from any cause ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
    AUC will be calculated and reported using standard descriptive statistics.
  • Symptomatic congestive heart failure [ Time Frame: Until 30 days after last dose of treatment ] [ Designated as safety issue: Yes ]
  • Dose reductions, dose interruptions, dose discontinuations [ Time Frame: While on treatment ] [ Designated as safety issue: Yes ]
  • Tumor response (using RECIST criteria) [ Time Frame: While receiving treatment ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: From enrollment until documented disease progression or death ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: From enrollment until death from any cause ] [ Designated as safety issue: No ]
  • Trough level of lapatinib [ Time Frame: During week 3, week 4, and week 5 of therapy ] [ Designated as safety issue: No ]
  • Percentage of doses of lapatinib received [ Time Frame: While on active therapy ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Tolerability of the Combination of Lapatinib and Trastuzumab in Adults Age 60 or Older With HER2 Positive Locally Advanced or Metastatic Breast Cancer
Tolerability of the Combination of Lapatinib and Trastuzumab in Adults Age 60 or Older With HER2 Positive Locally Advanced or Metastatic Breast Cancer

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.

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.

Interventional
Phase 2
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Breast Neoplasms
  • HER2/Neu Positive
  • Geriatric Health Services
  • Drug: Lapatinib
    250 mg tablets
    Other Names:
    • Tykerb
    • Tyverb
    • GSK572016
    • GW-572016
    • GW2016
  • Drug: Trastuzumab
    Intravenous injection
    Other Name: Herceptin
  • Other: laboratory biomarker analysis
    Other Name: Correlative studies
  • Other: pharmacological study
    Other Name: Correlative studies
Experimental: Lapatinib and trastuzumab
Patients 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.
Interventions:
  • Drug: Lapatinib
  • Drug: Trastuzumab
  • Other: laboratory biomarker analysis
  • Other: pharmacological study

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
40
Not Provided
March 2019   (final data collection date for primary outcome measure)

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 enrollment
  • 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
Both
60 Years and older
No
Contact: Arti Hurria, MD 626 256-4673 ahurria@coh.org
United States
 
NCT01273610
10112, NCI-2011-00116
Yes
City of Hope Medical Center
City of Hope Medical Center
  • GlaxoSmithKline
  • Genentech, Inc.
Principal Investigator: Arti Hurria, MD City of Hope Medical Center
City of Hope Medical Center
April 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP