Lapatinib and WBRT for Patients With Brain Metastases From Lung or Breast Tumors

NCT01218529 | Completed Phase 2

• 2 other identifiers: HE 42/092009-013128-22
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 13

Brief Summary

This phase II open-label study will be performed to evaluate the response rate of brain metastases from lung and breast tumors under treatment with WBRT and lapatinib.

Conditions

Brain Metastases; Lung Tumors; Breast Tumors

Keywords

Brain metastases from lung and breast tumors

Outcome Measures

Primary Outcomes (1)

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

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

Secondary Outcomes (4)

• Response rate for systemic disease

  At 6 weeks

• Time To Progression in brain and/or non-Central Nervous System (CNS)

  At the 6 weeks timepoint, radiological assessment with brain MRI will take place to evaluate the response of the patients.The patients will be followed-up every 12 weeks for disease progression and survival.

• Safety and tolerability of proposed schema. Adverse Events (AEs) of all participants will be recorded and assessed upon signature of the informed consent form, until 30 days after the last administration of study treatment.

  10 weeks (6 weeks therapy + 4 weeks follow-up period for AEs)

• To explore the 20% volumetric reduction of brain metastatic lesions as a meaningful threshold of CNS response.

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

Study Arms (1)

Whole Brain Radiation Therapy (WBRT) + lapatinib

EXPERIMENTAL

Whole Brain Radiation Therapy (30Gy in 10 fractions) and lapatinib 1250mg once daily for 2 weeks followed by lapatinib treatment 1500mg once daily for 4 weeks.

Drug: Lapatinib

Interventions

Lapatinib DRUG

Co-administration of lapatinib 1250mg once daily during the WBRT period (2 weeks)and then monotherapy with lapatinib 1500mg once daily for 4 weeks.

Whole Brain Radiation Therapy (WBRT) + lapatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent;
• Age \>=18 years old;
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2;
• Life expectancy of at least 12 weeks;
• Subjects must have histologically or cytologically confirmed invasive lung or breast cancer, with Stage IV disease;
• 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.
• At least one measurable lesion in the brain, defined as any lesion \>= 10mm in longest dimension on T1-weighted, gadolinium-enhanced MRI;
• 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;
• 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 permitted;
• At least 3 weeks since major surgical procedures;
• Able to swallow and retain oral medications;
• 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;
• Subjects must complete all screening assessments as outlined in the protocol;
• 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

You may not qualify if:

• Subjects are suitable for brain surgery or stereotactic radiosurgery (SRS);
• Subjects who have had prior cranial radiotherapy. Prior radiotherapy for lesions outside CNS is allowed.
• 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;
• Concurrent treatment with an investigational agent or participation in another treatment clinical trial;
• 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 allowed;
• Subjects with leptomeningeal carcinomatosis as the only site of CNS involvement;
• History of allergic reactions attributed to compounds of similar chemical composition (quinazolines) to lapatinib;
• Concurrent treatment with medications that are either inducers or inhibitors of CYP3A4 is prohibited. (For important exceptions, refer to Section Prohibited Medications);
• Malabsorption Syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Subjects with active, uncontrolled ulcerative colitis are also excluded;
• 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)
• Other known contraindication to MRI, such as a cardiac pacemaker, implanted cardiac defibrillator, brain aneurysm clips, cochlear implant, ocular foreign body, or shrapnel;
• 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;
• Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent;
• Pre-existing severe cerebral vascular disease, such as stroke involving a major vessel, CNS vasculitis, or malignant hypertension;
• Active cardiac disease, defined as one or more of the following:

Sponsors & Collaborators

• Hellenic Cooperative Oncology Group: lead

Study Sites (13)

General Hospital of Athens 'Hippokratio', 2nd Dept of Internal Medicine

Athens, 11527, Greece

Location

Sotiria General Hospital, 3rd Dept of Medicine, Oncology Unit

Athens, 11527, Greece

Location

General Peripheral Hospital of Athens "Alexandra"

Athens, 11528, Greece

Location

Agii Anargiri Cancer Hospital, 3rd Dept of Medical Oncology

Athens, 14564, Greece

Location

Hygeia Hospital, 1st Dept of Medical Oncology

Athens, 15123, Greece

Location

Hygeia Hospital, 2nd Dept of Medical Oncology

Athens, 15123, Greece

Location

Metropolitan Hospital, 1st Dept of Medical Oncology

Athens, 18547, Greece

Location

Metropolitan Hospital, 2nd Dept of Medical Oncology

Athens, 18547, Greece

Location

Chania General Hospital, Oncology Section

Chania, 73100, Greece

Location

Ioannina University Hospital, Dept of Medical Oncology

Ioannina, 45110, Greece

Location

University Hospital of Larissa, Dept of Internal Medicine, Oncology Section

Larissa, 44110, Greece

Location

Rio University Hospital, Dept of Medical Oncology

Pátrai, 26500, Greece

Location

Papageorgiou General Hospital, Dept of Medical Oncology

Thessaloniki, 56429, Greece

Location

MeSH Terms

Conditions

Brain Neoplasms; Lung Neoplasms; Breast Neoplasms

Interventions

Lapatinib

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Christos Christodoulou, MD

  Metropolitan Hospital, 2nd Dept of Medical Oncology

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2010
• First Posted: October 11, 2010
• Study Start: October 1, 2010
• Primary Completion: August 1, 2014
• Study Completion: December 1, 2014
• Last Updated: December 31, 2014

Record last verified: 2014-12

Locations

GR (13)