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Lapatinib and Whole Brain Radiotherapy for Patients With Brain Metastases From Lung and Breast Tumors. A Phase II Study of the Hellenic Cooperative Oncology Group (HeCOG).

Phase 2
18 Years
Open (Enrolling)
Brain Metastases, Lung Tumors, Breast Tumors

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Trial Information

Lapatinib and Whole Brain Radiotherapy for Patients With Brain Metastases From Lung and Breast Tumors. A Phase II Study of the Hellenic Cooperative Oncology Group (HeCOG).

Patients with breast or lung cancer who have developed brain metastases will be treated with
WBRT (30Gy in 10 fractions) and lapatinib 1250mg once daily, followed by lapatinib treatment
1500mg once daily for a total duration of 6 weeks. At the 6 weeks timepoint, radiological
assessment with brain MRI will take place to evaluate the response of the patients.
Subsequent to the 6 weeks treatment period with lapatinib, the patients may discontinue
lapatinib as monotherapy and the physicians can proceed with any therapy, according to their
discretion. The patients will be followed-up every 12 weeks for disease progression and

Inclusion Criteria:

1. Signed written informed consent;

2. Age >=18 years old;

3. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2;

4. Life expectancy of at least 12 weeks;

5. Subjects must have histologically or cytologically confirmed invasive lung or breast
cancer, with Stage IV disease;

6. Epidermal growth factor receptor (ErbB1/EGFR) overexpressing primary tumour, defined
as 2+/3+ staining by immunohistochemistry (IHC) is mandatory to assess the patient
population, but it is not a requirement for study entry.

7. At least one measurable lesion in the brain, defined as any lesion >= 10mm in longest
dimension on T1-weighted, gadolinium-enhanced MRI;

8. Cardiac ejection fraction within institutional range of normal as measured by
echocardiogram. Multigated acquisition scan (MUGA) scans will be accepted in cases
where an echocardiogram cannot be performed or is inconclusive;

9. At least 3 weeks since last chemotherapy, immunotherapy, biologic therapy, or
hormonal therapy for cancer, and sufficiently recovered or stabilized from side
effects associated with prior therapy. Concurrent treatment with bisphosphonates is

10. At least 3 weeks since major surgical procedures;

11. Able to swallow and retain oral medications;

12. Female subjects with child bearing potential or male subjects able to father a child
must be completely abstinent from intercourse or use acceptable methods for birth
control during the course of the study;

13. Subjects must complete all screening assessments as outlined in the protocol;

14. Subjects must have normal organ and marrow function as defined below:

SYSTEM LABORATORY VALUES Hematologic Absolute neutrophil count (ANC) 1.0 x 109/L
Hemoglobin >= 9 g/dL (after transfusion if needed) Platelets >= 50 x 109/L Hepatic Albumin
>= 2.5 g/dL Serum bilirubin <= 1.5x ULN unless due to Gilbert's syndrome Aspartate
aminotransferase (AST) and Alaninine Aminotransferase (ALT) <= 5x upper limit of normal
(ULN) if documented liver metastases <= 3x ULN without liver metastases Renal Serum
Creatinine <= 2.0 mg/dL or Calculated Creatinine Clearance* >= 25 mL/min*Calculated by the
Cockcroft and Gault Method

Exclusion Criteria:

1. Subjects are suitable for brain surgery or stereotactic radiosurgery (SRS);

2. Subjects who have had prior cranial radiotherapy. Prior radiotherapy for lesions
outside CNS is allowed.

3. Subjects who have had chemotherapy or radiotherapy within 2 weeks prior to entering
the study or who have unresolved or unstable, serious toxicity from prior
administration of another investigational drug and/or of prior cancer treatment;

4. Concurrent treatment with an investigational agent or participation in another
treatment clinical trial;

5. Subjects receiving concurrent chemotherapy, radiation therapy, immunotherapy,
biologic therapy (including an ErbB1 and/or ErbB2 inhibitor), or hormonal therapy for
treatment of their non-CNS cancer. Concurrent treatment with bisphosphonates is

6. Subjects with leptomeningeal carcinomatosis as the only site of CNS involvement;

7. History of allergic reactions attributed to compounds of similar chemical composition
(quinazolines) to lapatinib;

8. Concurrent treatment with medications that are either inducers or inhibitors of
CYP3A4 is prohibited. (For important exceptions, refer to Section Prohibited

9. Malabsorption Syndrome, disease significantly affecting gastrointestinal function, or
resection of the stomach or small bowel. Subjects with active, uncontrolled
ulcerative colitis are also excluded;

10. Any underlying liver or biliary disease (except for patients with Gilbert syndrome,
asymptomatic cholelithiasis, liver metastases or stable chronic liver disease
according to the physician)

11. Other known contraindication to MRI, such as a cardiac pacemaker, implanted cardiac
defibrillator, brain aneurysm clips, cochlear implant, ocular foreign body, or

12. Concurrent disease or condition that would make the subject inappropriate for study
participation or any serious medical or psychiatric disorder that would interfere
with the subject's safety;

13. Dementia, altered mental status, or any psychiatric condition that would prohibit the
understanding or rendering of informed consent;

14. Pre-existing severe cerebral vascular disease, such as stroke involving a major
vessel, CNS vasculitis, or malignant hypertension;

15. Active cardiac disease, defined as one or more of the following:

- History of uncontrolled or symptomatic angina

- History of arrhythmias requiring medications, or clinically significant, with
the exception of asymptomatic atrial fibrillation requiring anticoagulation

- Myocardial infarction < 6 months from study entry

- Uncontrolled or symptomatic congestive heart failure

- Ejection fraction below the institutional normal limit

- Any other cardiac condition, which in the opinion of the treating physician,
would make this protocol unreasonably hazardous for the patient

16. Uncontrolled infection;

17. History of other malignancy, except for curatively treated basal cell carcinoma or
squamous cell carcinoma of the skin, or carcinoma in situ of the cervix. Subjects
with other malignancies who have been disease-free for at least 5 years are eligible;

18. Pregnant or lactating females.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response rate in brain as assessed by volumetric analysis of brain Mangnetic Resonance Imaging (MRI).

Outcome Time Frame:

At the 6 weeks timepoint, radiological assessment with brain MRI will take place to evaluate the response of the patients

Safety Issue:


Principal Investigator

Christos Christodoulou, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Metropolitan Hospital, 2nd Dept of Medical Oncology


Greece:National Ethics Committee

Study ID:

HE 42/09



Start Date:

October 2010

Completion Date:

April 2014

Related Keywords:

  • Brain Metastases
  • Lung Tumors
  • Breast Tumors
  • Brain metastases from lung and breast tumors
  • Breast Neoplasms
  • Lung Neoplasms
  • Neoplasm Metastasis
  • Neoplasms, Second Primary
  • Brain Neoplasms