Clinical trial NCT01757327 (phase 2, status: withdrawn)
Conditions: breast neoplasms
ICD codes: C79.81, D24.1, D24.2, D24.9, D49.3, C44.501, D48.60
Drugs: erismodegib, placebo
SMILES: [H][C@]1(C)CN(C[C@@]([H])(C)O1)C1=CC=C(NC(=O)C2=CC=CC(=C2C)C2=CC=C(OC(F)(F)F)C=C2)C=N1, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Reason stopped: 
    poor accrual
  
Eligibility criteria:

        Pre-Registration Inclusion Criteria

          -  Diagnosis of pathologic stage II or III ER, PR, and HER2 negative primary invasive
             ductal or invasive lobular breast carcinoma. ER negative is defined as an Allred score
             of 0-2. PR negative is defined as an Allred score of 0-4. HER2 negative is defined as
             an IHC score of 0-1 and/or not-amplified by FISH testing.

          -  All surgery for breast cancer (as defined by surgical excision of the cancer with a
             negative margin or mastectomy) must be complete.

          -  Undergone axillary lymph node surgery (either sentinel lymph node biopsy or axillary
             lymph node dissection) per institutional standard.

          -  Completed all (neo) adjuvant chemotherapy and radiation therapy as recommended by the
             treating physicians.

          -  Completed the most recent cancer therapy (surgery, radiation, or chemotherapy) no less
             than 3 and no more than 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 trial will not compromise
             the endpoints (primary and secondary) of the primary clinical trial. In addition,
             patients must have completed the experimental therapy no less than 4 weeks or 5 half
             lives (whichever is longer) and no more than 24 weeks 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
             sonidegib trial.

          -  At least 18 years of age.

          -  ECOG performance status ≤ 1

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

        Pre-Registration Exclusion Criteria

          -  Concurrent treatment with any other standard therapy (e.g. chemotherapy, targeted
             therapy or radiotherapy) or within 3 weeks of starting sonidegib.

          -  Treatment with investigational anti-cancer agent within 4 weeks or 5 half-lives
             whichever is longer, of initializing treatments with sonidegib.

          -  Previous treatment with systemic sonidegib or with other Hh pathway inhibitors.

          -  Diagnosis of a neuromuscular disorder (e.g., inflammatory myopathies, muscular
             dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy) or 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 sonidegib treatment. If it is essential that the
             patient stays on a statin to control hyperlipidemia, only pravastatin may be used with
             extra caution.

          -  Known to be HIV-positive on combination antiretroviral therapy because of the
             potential for pharmacokinetic interactions with sonidegib. 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.

        Registration Inclusion Criteria

          -  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.

          -  ECOG performance status ≤ 1

          -  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

               -  AST(SGOT)/ALT(SGPT) ≤ 2.5 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

          -  Able to swallow capsules.

          -  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 20 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.

        Registration Exclusion Criteria

          -  Evidence of distant metastasis present by CT scan, bone scan, or physical exam within
             one year prior to entry into the trial.

          -  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.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to sonidegib or other agents used in the study.

          -  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 sonidegib
             treatment.

          -  Diagnosis of a medical condition that would lead to lack of physical integrity of the
             upper gastrointestinal tract or known malabsorption syndrome.

          -  Taking warfarin and Coumadin derivatives because of potential interactions with
             sonidegib.

          -  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
             sonidegib. 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 sonidegib.

          -  Concurrent uncontrolled medical conditions that may interfere with participation in
             the study or potentially affect the interpretation of the study data.

          -  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)

          -  Pregnant and/or breastfeeding. Pregnant women are excluded from this study because
             sonidegib 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 sonidegib, breastfeeding should be
             discontinued if the mother is treated with sonidegib.