Lapatinib and RAD-001 for HER2 Positive Metastatic Breast Cancer
Verified December 2013 by University of Kansas
Information provided by (Responsible Party):
University of Kansas
First received: January 10, 2011
Last updated: December 30, 2013
Last verified: December 2013
By doing this study, researchers hope to learn the effectiveness of the combination of Lapatinib and RAD-001 for treating patients who have progressed on previous therapies.
Metastatic Breast Cancer
Drug: Lapatinib and RAD-001
||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||Phase II Trial of Lapatinib and RAD-001 for HER2 Positive Metastatic Breast Cancer
Primary Outcome Measures:
Secondary Outcome Measures:
- Overall benefit of combination [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
- Six-month Progression Free Survival.
- Safety and Tolerability of the combination.
- Six-month Objective CNS response rate in patients with CNS metastases.
- Six-month Clinical benefit rate of systemic disease.
- Six-month Clinical benefit rate in the CNS.
- Rate of development of Brain Metastases on six months of therapy.
| Estimated Enrollment:
| Study Start Date:
| Estimated Study Completion Date:
| Estimated Primary Completion Date:
||November 2014 (Final data collection date for primary outcome measure)
Experimental: Lapatinib and RAD-001
RAD-001 will be administered orally as a once-daily dose of 5 mg (one 5 mg tablet) continuously from study day 1 until progression of disease or unacceptable toxicity. Patients will be instructed to take RAD-001 in the morning, at the same time each day.
Lapatinib will be administered orally as a once-daily dose of 1250 mg (five 250 mg tablets) continuously from study day 1 until progression of disease or unacceptable toxicity. Patients will be instructed to take lapatinib at bedtime, at the same time each day. Lapatinib should be taken by the patient in a fasting state.
Drug: Lapatinib and RAD-001
Lapatinib will be taken orally as a once-daily dose of 1250 mg (five 250 mg tablets) continuously from study day 1 until progression of disease. Patients will take the tablet at bedtime, at the same time each day, in a fasting state.
Everolimus will be taken orally as a once-daily dose of 5 mg (one 5 mg tablet) from study day 1 until progression of disease. Patients will take the tablet at the same time each morning.
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- Females > 18 years of age
- Histologically proven adenocarcinoma of breast in primary or metastatic setting. Stage: Locally advanced (inoperable) or metastatic
- HER2 positive breast cancer (IHC 3+ or FISH ratio of > 2.0)
- ECOG Performance status 0-2
- Up to four prior chemotherapy regimens and anti-HER2 agents in metastatic setting allowed. Must have progressed on at least one HER2 targeted therapy (lapatinib or Herceptin) for metastatic breast cancer.
- Women of childbearing potential must have negative urine or serum pregnancy test within 7 days prior to administration of Everolimus. If barrier contraceptives are used, they must be continued throughout trial by both sexes. Hormonal contraceptives not acceptable as a sole method of contraception.
- Adequate kidney function: serum creatinine of < 1.5 mg/dl and/or creatinine clearance of > 60 mL/min
- Adequate hepatic function: transaminases < 2.5 x upper limit of normal (up to 5 x ULN in patients with liver metastases) and total bilirubin < 1.5 mg/dL. Adequate coagulation: INR ≤ 2.0 and PTT < 1.5 X the upper limit of institution normal range. Oral anticoagulants, eg, warfarin are CYP2C9 substrates and, as such, no interaction with Everolimus is expected. Anticoagulation with Coumadin is allowed if target INR is ≤ 2.0 and stable for > 2weeks. Anticoagulation with LMW is allowed.
- Must be informed of investigational nature of study, and must sign an informed consent
- Pretreatment lab values (must be performed within 14 days of patient registration unless otherwise specified. Other baseline studies must be performed within 30 days of registration.
- Patients will have baseline CT chest, abdomen and pelvis within 30 days of registration.
- Adequate cardiac function (LVEF ≥ 50% as measured by echocardiogram or MUGA scan).
- Fasting serum cholesterol ≤ 300 mg/dL OR ≤ 7.75 mmol/L AND fasting triglycerides ≤ 2.5 x ULN. NOTE: In case one or both of these thresholds are exceeded, patient may be included after initiation of appropriate lipid lowering medication with approval from the principal investigator.
Must have measurable or non-measurable disease by RECIST criteria (version 1.1), with radiologic scans performed within 30 days of registration. Baseline scans can include:
- CT Scan or MRI and Bone Scan OR
- PET/CT provided it is performed with both IV and oral contrast and the CT is acquired with 5mm or less slice thickness. If IV contrast administration is contraindicated, patients should have CT scan without contrast and bone scan or MRI and bone scan.
- MRI of brain will be used for baseline assessment and tumor response assessment for CNS lesions.
- Baseline imaging method(s) should be used to determine tumor response throughout course of study.
Measurable disease: lesions with clearly defined margins that can be accurately measured in at least one diameter (longest diameter to be recorded) with a minimum size of:
- 10mm by CT scan (CT scan slice thickness no greater than 5mm)
- 10mm caliper measurement by clinical exam (lesions which cannot be accurately measured with calipers should be recorded as non-measurable)
- 20mm by chest xray
- Malignant lymph nodes: to be considered pathologically enlarged and measurable. Lymph node must be > 15mm in short axis when assessed by CT scan. At baseline and in follow-up, only short axis will be measured and followed.
Non-measurable disease: all other lesions including small lesions (longest diameter < 10mm or pathological lymph nodes with > to <15 mm (short axis), and masses with margins not clearly defined. Lesions that are considered non-measurable include:
- Bone lesions
- Leptomeningeal disease
- Pleural/pericardial effusion
- Inflammatory breast disease
- Abdominal masses that are not confirmed and followed by imaging techniques
- Cystic lesion
- Lymphangitic involvement of skin or lung
The following pre-study tests should be obtained within 14 days prior to registration in accordance with good medical practice. Results of these tests do not determine eligibility and minor deviations are acceptable if they do not impact patient safety in the judgment of the treating physician:
- ANC > 1,000/mm3
- platelet count > 100,000/mm3
- hemoglobin > 9 g/dL
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01283789
|University of Kansas Medical Centner
|Kansas City, Kansas, United States, 66160 |
|Contact: Stella Baccaray, RN 913-588-2437 email@example.com |
|Sub-Investigator: Priyanka Sharma, MD |
|Sub-Investigator: Bruce Kimler, PhD |
|Sub-Investigator: Carol Fabian, MD |
|Sub-Investigator: Henry Yeh, PhD |
University of Kansas
||Qamar Khan, MD
||University of Kansas
No publications provided
||University of Kansas
History of Changes
|Other Study ID Numbers:
|Study First Received:
||January 10, 2011
||December 30, 2013
||United States: Food and Drug Administration
Keywords provided by University of Kansas:
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on July 20, 2014
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