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Trial of RAD001 in Triple Negative Metastatic Breast Cancer

Sponsor
Milton S. Hershey Medical Center (Other)
Overall Status
Terminated
CT.gov ID
NCT00827567
Collaborator
Novartis (Industry)
6
Enrollment
1
Location
1
Arm
22
Duration (Months)
0.3
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: RAD 001
 Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
6 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II Trial of RAD001 in Triple Negative Metastatic Breast Cancer
Study Start Date :
Apr 1, 2009
Actual Primary Completion Date :
Feb 1, 2011
Actual Study Completion Date :
Feb 1, 2011

Arms and Interventions

Arm Intervention/Treatment
Experimental: RAD 001

RAD001-10 mg by mouth once everyday

Drug: RAD 001
RAD 001-10 mg by mouth once everyday
Other Names:
  • Everolimus

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Penn State Milton S. Hershey Medical Center Hershey Pennsylvania United States 17033

    Sponsors and Collaborators

    • Milton S. Hershey Medical Center
    • Novartis

    Investigators

    • Principal Investigator: Allan Lipton, MD, Penn State Milton S. Hershey

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Allan Lipton, Professor of Medicine, Milton S. Hershey Medical Center
    ClinicalTrials.gov Identifier:
    NCT00827567
    Other Study ID Numbers:
    • RAD001JUS48T
    First Posted:
    Jan 22, 2009
    Last Update Posted:
    Jan 13, 2014
    Last Verified:
    Dec 1, 2013
    Keywords provided by Allan Lipton, Professor of Medicine, Milton S. Hershey Medical Center
    Breast cancer
    metastatic breast
    triple negative
    ER/PR negative
    Her2 Neu negative
    Additional relevant MeSH terms:
    Breast Neoplasms
    Everolimus

    Study Results

    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 Detail 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.
    Arm/Group Title RAD 001
    Arm/Group Description RAD001-10 mg by mouth once everyday
    Period Title: Overall Study
    STARTED 4
    COMPLETED 0
    NOT COMPLETED 4

    Baseline Characteristics

    Arm/Group Title RAD 001
    Arm/Group Description RAD001-10 mg by mouth once everyday
    Overall Participants 4
    Age (Count of Participants)
    <=18 years
    0
    0%
    Between 18 and 65 years
    3
    75%
    >=65 years
    1
    25%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    58.5
    (7.65)
    Sex: Female, Male (Count of Participants)
    Female
    4
    100%
    Male
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    4
    100%

    Outcome Measures

    1. Primary Outcome
    Title Time to Progression(TTP)
    Description 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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title RAD 001
    Arm/Group Description RAD001-10 mg by mouth once everyday
    Measure Participants 0

    Adverse Events

    Time Frame Weekly for 4 weeks, then monthly until disease progression
    Adverse Event Reporting Description
    Arm/Group Title RAD 001
    Arm/Group Description RAD001-10 mg by mouth once everyday
    All Cause Mortality
    RAD 001
    Affected / at Risk (%) # Events
    Total / (NaN)
    Serious Adverse Events
    RAD 001
    Affected / at Risk (%) # Events
    Total 0/4 (0%)
    Other (Not Including Serious) Adverse Events
    RAD 001
    Affected / at Risk (%) # Events
    Total 2/4 (50%)
    Blood and lymphatic system disorders
    Anemia 2/4 (50%) 3
    Thrombocytopenia 1/4 (25%) 1

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Allan Lipton, MD
    Organization Penn State
    Phone 717-531-5960
    Email alipton@psu.edu
    Responsible Party:
    Allan Lipton, Professor of Medicine, Milton S. Hershey Medical Center
    ClinicalTrials.gov Identifier:
    NCT00827567
    Other Study ID Numbers:
    • RAD001JUS48T
    First Posted:
    Jan 22, 2009
    Last Update Posted:
    Jan 13, 2014
    Last Verified:
    Dec 1, 2013