LDE225 in Treating Patients With Stage II-III Estrogen Receptor- and HER2-Negative Breast Cancer

NCT01757327 | Withdrawn Phase 2

• 1 other identifier: 201310007
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This randomized phase II trial studies the effects of erismodegib (LDE225) on disseminated tumor cells (DTCs) in patients with stage III-III estrogen receptor (ER)-negative and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. The presence of DTCs after completing treatment for breast cancer may be linked to recurrence of the disease. LDE225 may eliminate DTCs in bone marrow and reduce the risk of recurrence.

Conditions

Breast Neoplasms

Outcome Measures

Primary Outcomes (1)

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

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

  at 6 months

Secondary Outcomes (7)

• Disease-free survival (DFS)

  2 years from initiation of study treatment

• Overall Survival (OS)

  2 years from initiation of study treatment

• Ptch1 expression after treatment with LDE225 or placebo

  At 6 months

• Incidence of toxicities associated with LDE225 or placebo treatment

  For 30 days following the last day of study treatment; up to 25 months

• Time to recurrence and death in DTC-negative patients and DTC-positive patients

  2 years from initiation of study treatment

Study Arms (2)

Arm I (erismodegib [LDE225])

EXPERIMENTAL

400 mg daily and treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Erismodegib

Arm II (placebo)

PLACEBO COMPARATOR

Patients receive placebo PO daily and treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Placebo

Interventions

Erismodegib DRUG

Also known as: Smoothened antagonist LDE225, Sonidegib

Arm I (erismodegib [LDE225])

Placebo DRUG

Also known as: PLCB

Arm II (placebo)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Washington University School of Medicine: lead

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Breast Neoplasms

Interventions

sonidegib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Cynthia Ma, M.D., Ph.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

• Rebecca Aft, M.D., Ph.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2012
• First Posted: December 28, 2012
• Study Start: April 1, 2014
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2019
• Last Updated: April 27, 2015

Record last verified: 2015-04