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Phase 2
18 Years
Not Enrolling
Breast Neoplasms

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Trial Information

Inclusion Criteria:

- Patient must have been diagnosed with pathologic stage II or III ER and HER2 negative
primary invasive ductal or invasive lobular breast carcinoma, ER negative is defined
as an Allred score of 0-2. HER2 negative is defined as an IHC score of 0-1 and/or
not-amplified by FISH testing.

- Patients must have completed all surgery for their breast cancer as defined by
surgical excision of the cancer with a negative margin or mastectomy.

- Patient must have had an axillary lymph node surgery (either sentinel lymph node
biopsy or axillary lymph node dissection) per institutional standard.

- Patient must have completed all (neo) adjuvant chemotherapy and radiation therapy as
recommended by the treating physicians.

- Patient must have completed the most recent cancer therapy (surgery, radiation, or
chemotherapy) within 3 to 24 weeks prior to registration.

Note: patients who received experimental neoadjuvant or adjuvant therapy or surgical
therapy (with the exception of Hh inhibitors) through participation in clinical trial are
NOT excluded from this study as long as the other trial does not exclude patients from
enrolling into an additional adjuvant clinical trial and enrolling into this LDE225 trial
will not compromise the endpoints (primary and secondary) of the primary clinical trial. .
In addition, patients must have completed the experimental therapy within the 4 weeks or
5 half lives (whichever is longer), to 24 weeks period prior to registration. For those
patients who have enrolled into a neoadjuvant/adjuvant/surgical trial, all endpoints of
these trials will be reviewed prior to consenting the patient for the LDE225 trial.

-Patient must have the presence of bone marrow DTCs -after the completion of all intended
breast cancer therapy including surgery, (neo) adjuvant chemotherapy therapy and radiation
as indicated.

Note: Bone marrow aspiration will be performed in consented patients to evaluate DTCs
provided patients meet all eligibility criteria as described in this section.

- Patient must be ≥ 18 years of age.

- Patient must have an ECOG performance status ≤ 1.

- Patient must have normal bone marrow and organ function as defined below:

- Leukocytes ≥ 3,000/mcL

- Absolute neutrophil count ≥ 1,500/mcL

- Hemoglobin ≥ 9.0 g/dL

- Platelets ≥ 80,000/mcL

- Total bilirubin ≤ 1.5 x IULN


- Plasma creatine phosphokinase (CK) < 1.5 x ULN

- Creatinine ≤ 1.5 x ULN OR Creatinine clearance ≥ 50 mL/min/1.73 m2 for patients with
creatinine levels above institutional normal

- Patient must be able to swallow capsules.

11. Women of childbearing potential must have a negative serum pregnancy test ≤ 7
days from date of registration. Women of childbearing potential must agree to use
dual forms of adequate contraception (barrier method of birth control, non-hormonal
IUD or IUS, abstinence) prior to study entry duration of study participation and 6
months after final dose of study treatment. Should a woman become pregnant or
suspect she is pregnant while participating in this study, she must inform her
treating physician immediately.

- Patient (or legally authorized representative if applicable) must be able to
understand and willing to sign an IRB approved written informed consent document.

- Women of all races and ethnic groups are eligible for this trial.

Exclusion Criteria:

- Patient must not have evidence of distant metastasis present by CT scan, bone scan,
or physical exam within one year prior to entry into the trial.

- Patient must not have a concurrent treatment with any other standard therapy (e.g.
chemotherapy, targeted therapy or radiotherapy) or within 3 weeks of starting LDE225.

- Patients must not have taken part in an investigational anticancer agent within 4
weeks or 5 half-lives whichever is longer, of initializing treatments with LDE225.

- Patient must not have a history of other malignancy ≤ 5 years previous with the
exception of basal cell or squamous cell carcinoma of the skin which were treated
with local resection only or carcinoma in situ of the cervix.

- Patient must not have previously been treated with systemic LDE225 or with other Hh
pathway inhibitors.

- Patient must not have a neuromuscular disorder (e.g., inflammatory myopathies,
muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy) or be on
concomitant treatment with drugs that are recognized to cause rhabdomyolysis (such as
HMG CoA inhibitors (statins), clofibrate and gemfibrozil) and that cannot be
discontinued at least 2 weeks prior to starting LDE225 treatment. If it is essential
that the patient stays on a statin to control hyperlipidemia, only pravastatin may be
used with extra caution.

- Patient must not have a history of allergic reactions attributed to compounds of
similar chemical or biologic composition to LDE225 or other agents used in the study.

- Patient must not be planning to embark on a new strenuous exercise regimen after
initiation of study treatment. Muscular activities, such as strenuous exercise, that
can result in significant increases in plasma CK levels should be avoided while on
LDE225 treatment.

- Patients must be able to take oral drugs or without any medical condition that lead
to lack of physical integrity of the upper gastrointestinal tract or known
malabsorption syndromes.

- Patient must not be talking warfarin and Coumadin derivatives because of potential
interactions with LDE225.

- Patient must not be receiving treatment with medications known to be moderate or
strong inhibitors or inducers of CYP3A4/5 or drugs metabolized by CYP2B6 or CYP2C9
that have narrow therapeutic indices and that cannot be discontinued before starting
treatment with LDE225. Medications that are strong CYP3A4/5 inhibitors should be
discontinued at least 7 days and strong CYP3A4/5 inducers at least 2 weeks prior to
starting treatment with LDE225.

- Patients must not have concurrent uncontrolled medical conditions that may interfere
with their participation in the study or potentially affect the interpretation of the
study data.

- Patient must not have impaired cardiac function or clinically significant heart
disease, including any one of the following:

- Angina pectoris within 3 months

- Acute myocardial infarction within 3 months

- QTcF > 450 msec for males and > 470 msec for females on the screening ECG

- A past medication history of clinically significant ECG abnormalities or a family
history of prolonged QT-interval syndrome

- Other clinically significant heart disease (e.g., congestive heart failure,
uncontrolled hypertension, history of labile hypertension, or history of poor
compliance with an antihypertensive regimen)

- Patient must not be pregnant and/or breastfeeding. Pregnant women are excluded from
this study because LDE225 is an Hh inhibitor with the potential for teratogenic or
abortifacient effects. Because there is an unknown but potential risk for adverse
events in nursing infants secondary to treatment of the mother with LDE225,
breastfeeding should be discontinued if the mother is treated with LDE225.

- Patients must be willing to apply highly effective contraception during the study and
through the duration as defined below after the final dose of study treatment

- Patient must not be known to be HIV-positive on combination antiretroviral therapy
because of the potential for pharmacokinetic interactions with LDE225. In addition,
these patients are at increased risk of lethal infections when treated with
marrow-suppressive therapy. Appropriate studies will be undertaken in patients
receiving combination antiretroviral therapy when indicated.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Outcome Measure:

Proportion of patients who are bone marrow DTC-negative after therapy

Outcome Description:

Comparing LDE225 to placebo using a stratified Cochran-Mantel-Haenszel test for difference of proportions

Outcome Time Frame:

at 6 months

Safety Issue:


Principal Investigator

Cynthia Ma, M.D., Ph.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Washington University School of Medicine


United States: Institutional Review Board

Study ID:




Start Date:

March 2013

Completion Date:

November 2019

Related Keywords:

  • Breast Neoplasms
  • Breast Neoplasms
  • Neoplasms



Washington University School of MedicineSaint Louis, Missouri  63110