Breast Cancer
Conditions
Keywords
Breast cancer, metastatic breast, triple negative, ER/PR negative, Her2 Neu negative
Brief summary
The hypothesis of this clinical research study is to discover if the study drug RAD001 can shrink or slow the growth of Estrogen Receptor/Progesterone Receptor (ER/PR) negative or Human Epidermal growth factor Receptor 2 (Her2 Neu) negative breast cancer. The safety of RAD001 will also be studied. Patients physical state, symptoms, changes in the size of the tumor, and laboratory findings obtained while on-study will help the research team decide if RAD001 is safe and effective.
Detailed description
RAD001 is an orally administered cell cycle inhibitor with antitumor activity. RAD001, like Rapamycin, binds with high affinity to an intracellular immunophilin, FKBP12 and this complex specifically interacts with the mammalian target of rapamycin (mTOR) protein kinase, inhibiting downstream events such as the initiation of mRNA translation. RAD001 inhibits the growth of a wide range of histologically diverse tumor cells. RAD001 is being developed as a cytostatic agent to delay the time to tumor recurrence/progression or to increase survival in patients with various malignancies. The compound has good tolerability, a partially discovered mechanism of action. RAD001 has the ability to arrest cells in the G1 phase, and the ability to induce apoptosis. RAD001 is being investigated as an anticancer agent based on its potential to act directly on the tumor cells by inhibiting tumor cell growth and proliferation through possible inhibition of the PI3/AKT/MTOR pathway. RAD001 was shown to have activity in human tumor cell lines originating from lung, breast, prostate, colon, kidney, melanoma and glioblastoma. RAD001 was also shown to have activity in human pancreatic neuroendocrine cells, where induction of apoptosis was reported, as well as in acute myeloid leukemia cells, adult T-cell leukemia cells, diffuse large B cell lymphoma cells, pancreatic tumor cells, ovarian cancer cells, and hepatocellular carcinoma cells.
Interventions
DRUGRAD 001
RAD 001-10 mg by mouth once everyday
Sponsors
Novartis
Milton S. Hershey Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Eastern Cooperative Group (ECOG) performance status ≤ 2 * Age ≥ 18 years * At least one measurable site of disease according to RECIST criteria that has not been previously irradiated. If the patient has had previous radiation to the marker lesion(s), there must be evidence of disease progression since the radiation * Adequate bone marrow function as shown by: Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L, Platelets (PLT)≥ 100 x 109/L, Hemoglobin (HGB) ≥9 g/dL * Adequate liver function as shown by:Serum bilirubin ≤ 1.5 x upper limits of normal (ULN), Prothrombin Time (INR) ≤ 1.3 (or ≤ 3 on anticoagulants), Liver function teats ≤ 2.5x ULN (≤ 5x ULN in patients with liver metastases) * Adequate renal function: serum creatinine ≤ 1.5 x ULN * Controlled diabetes as defined by fasting serum glucose ≤1.5 x ULN * Fasting serum cholesterol ≤300 mg/dL or ≤7.75 mmol/L AND fasting triglycerides ≤ 2.5 x ULN.
Exclusion criteria
* Currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks of the start of study drug (including chemotherapy, antibody based therapy, etc.) * Palliative radiation therapy only allowed to localized areas (ie: painful rib lesion), at the discretion of the PI and treating radiation oncologist * Major surgery/significant traumatic injury within 4 weeks of start of study drug. * Not recovered from the side effects of any major surgery (defined as requiring general anesthesia) to Grade I or patients that may require major surgery during the course of the study. * Prior treatment with any investigational drug within the preceding 4 weeks * Receiving chronic immunosuppressive agents, except corticosteroids with a daily dosage equivalent to prednisone ≤ 20 milligrams (mg). However, patients receiving corticosteroids must have been on a stable dosage regimen for a minimum of 4 weeks prior to the first treatment with RAD001. Topical or inhaled corticosteroids are allowed. * May not receive immunization with attenuated live vaccines within one week of study entry or during study period. * Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases * Other malignancies within the past 3 years, except for adequately treated carcinoma of the cervix and basal or squamous cell carcinomas of the skin. * Severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: Congestive heart failure: New York Heart Association Class III/IV, Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease. * Impaired lung function (PFT screen at baseline) as defined as spirometry and DLCO that is 50% of the normal predicted value and/or 02 saturation that is 88% or less at rest on room air. * Uncontrolled diabetes as defined by fasting serum glucose ≥1.5 x ULN. Glucose control should be achieved before starting a patient on RAD001. * Active (acute or chronic) or uncontrolled severe infections * Liver disease(cirrhosis, chronic active hepatitis or chronic persistent hepatitis) * Known history of Human Immunodeficiency Virus (HIV) seropositivity * Impairment of gastrointestinal function/disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection) * Active, bleeding diathesis * Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. * Prior treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus). * Known hypersensitivity to RAD001 (everolimus) or other rapamycin drugs (sirolimus, temsirolimus) or to its excipients
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression(TTP) | Each patient assessed at 8 weeks from start of study drug | Progression is defined by RESIST criteria as any new lesion or the sum of target lesions increasing by 20% over baseline |
Countries
United States
Participant flow
Recruitment details
Recruitment period 4/13/2009 through 2/25/2011. Protocol dated 3/6/2009 & consent dated 4/8/2009 for the 4/13/2009 approval.Patients were seen at Penn State Cancer Institute Outpatient Unit.
Pre-assignment details
Two of the patients that were screen failures had cholesterol levels higher than inclusion criteria as this drug may increase cholesterol levels they were not eligible.
Participants by arm
| Arm | Count |
|---|---|
| RAD 001 RAD001-10 mg by mouth once everyday | 4 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Progression of Disease/Screen Failure | 4 |
Baseline characteristics
| Characteristic | RAD 001 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants |
| Age, Continuous | 58.5 years STANDARD_DEVIATION 7.65 |
| Region of Enrollment United States | 4 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 4 |
| serious Total, serious adverse events | 0 / 4 |
Outcome results
Primary
Time to Progression(TTP)
Progression is defined by RESIST criteria as any new lesion or the sum of target lesions increasing by 20% over baseline
Time frame: Each patient assessed at 8 weeks from start of study drug