Phase IB Trial of LDE225 and Paclitaxel in Recurrent Ovarian Cancer

NCT02195973 | Completed Phase 1 DMC

• 2 other identifiers: F140214007 (UAB 1357)000505867
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to find out if a new drug, LDE225, is safe and has beneficial effects when combined with paclitaxel in women with platinum resistant ovarian cancer. Platinum resistant ovarian cancer refers to recurrent ovarian cancer that has undergone chemotherapy inclusive of a platinum compound (e.g. carboplatin or cisplatin).

Conditions

Recurrent Ovarian Cancer

Keywords

ovarian cancer; platinum resistant; LED225; Sonidegib; Paclitaxel

Outcome Measures

Primary Outcomes (2)

• Safety of weekly paclitaxel + LDE225 treatment

  Safety of weekly paclitaxel and LDE225 treatment in patients with recurrent, platinum-resistant ovarian adenocarcinoma will be monitored by physical exams, review of adverse events, and laboratory studies.

  up to 2 years

• Assessment of toxicities

  Assessment of toxicity will be performed using the National Cancer Institute Common Toxicity Criteria version 4.03.

  up to 2 years

Secondary Outcomes (1)

• Optimal dose of LDE225 with paclitaxel

  6 months

Study Arms (1)

Paclitaxel + LDE225

EXPERIMENTAL

Patients will receive intravenous paclitaxel on days 1, 8, and 15 every 28 days (3 weeks on followed by one week off). This constitutes one cycle. in addition to the paclitaxel oral LDE225 will be taken daily. Dosages of each drug will vary according to the study cohort and phase. The study consists of six cycles of treatment followed by clinic visits every 2-3 months for up to two years.

Drug: LDE225

Interventions

LDE225 DRUG

After six cycles of weekly paclitaxel and LDE225, patients with a clinically beneficial response may be continued on weekly paclitaxel alone until disease progression.

Also known as: Sonidegib (LDE225), Taxol (Paclitaxel)

Paclitaxel + LDE225

Eligibility Criteria

• Age: 19 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Recurrent epithelial ovarian, fallopian tube or primary peritoneal carcinoma Histologic confirmation of the original primary tumor is required
• Papillary serous, endometrioid, clear cell, undifferentiated and mixed histologies
• Platinum resistant or refractory disease as per standard clinical and Gynecologic Oncology Group definition. Patients have had a treatment-free interval of less than 6 months from last platinum-based treatment to recurrence or progression during platinum based therapy
• Patients must have received at least one-prior platinum based chemotherapy regimen, to include cisplatin, carboplatin or other organoplatinum compound, for treatment of primary or recurrent ovarian, fallopian tube or primary peritoneal cancer
• Patients must have received a taxane as part of their prior treatment
• Measurable disease is required. By definition, measurable disease is at least one lesion that can be accurately measured in at least one dimension with the longest dimension to be recorded. Each lesion must be ≥ 20 mm when measured by conventional techniques, including palpation, plain x-ray, CT, MRI or ≥ 10 mm when measured by spiral CT imaging
• Patients must have one target lesion to be utilized in order to assess response per RECIST criteria
• ECOG Performance statuses of 0, 1, or 2
• Adequate organ function as evidenced by:
• Hematology: WBC ≥3.0 x 10\^9/L; ANC ≥1.5 x 10\^9/L; Platelets ≥100 x 10\^9/L
• Renal function: Creatinine less than or equal to 1.5 x institutional upper limit of normal (ULN) or 24-hour clearance greater than or equal to 50 mL/min
• Hepatic function: Bilirubin ≤ 1.5 x ULN and ALT, SGOT and alkaline phosphatase ≤ 2.5 x ULN
• Plasma creatine phosphatase (CK) less than 1.5 x ULN
• Serum creatinine less than or equal to 1.5 x ULN or 24-hour clearance greater than or equal to 50 mL/min
• Signed informed consent.

You may not qualify if:

• Patients with pathology demonstrating mucinous, carcinosarcoma or low malignant potential tumor histology are excluded. In addition, non-ovarian malignancies, malignant germ cell or stromal tumors are also excluded
• Previous or concurrent malignancies at other sites within the last 5 years, with the exception of in situ carcinoma of the cervix and adequately treated basal cell carcinoma or squamous cell carcinoma of the skin. In addition, patients with prior or concomitant, based on hysterectomy, Stage IA endometrial adenocarcinoma with less than 3 mm depth on invasion, absence of lymphovascular space invasion and absence of grade 3, papillary serous or clear cell histology are allowed
• Patients with prior radiation to the abdominal cavity or pelvis are excluded
• Patients unable to take oral drugs or with lack of physical integrity of the upper gastrointestinal tract or known malabsorption syndromes
• Patients who have previously been treated with systemic sonidegib (LDE225) or with other Hh pathway inhibitors
• Serious concomitant illness including but not limited to: uncontrolled diabetes mellitus, dementia, active infection (including HIV infection) requiring IV or oral antibiotics and psychiatric illness and/or other uncontrolled medical conditions which may preclude compliance with study protocol
• Patients who have neuromuscular disorder (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy) or are on concomitant treatment with drugs that are recognized to cause rhabdomyolysis, such as HMG CoA inhibitors (statins), clofibrate and gemfibrozil, and the cannot be discontinued at least 2 weeks prior to starting sonidegib treatment. If it is essential that the patient remain on a statin to control hyperlididemia, only pravastatin may be used with extra caution
• Patients who are planning on embarking 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 whilst on sonidegib treatment
• Patients who have taken part in an experimental drug study within 4 weeks or 5 half-lives, whichever is longer, of initiating treatment with sonidegib
• Patients who are receiving other anti-neoplastic therapy (e.g. chemotherapy, targeted therapy or radiotherapy) concurrently or within 2 weeks of starting treatment with sonidegib
• Peripheral Neuropathy of NCI-CTC (National Cancer Institute-Common Toxicity Criteria) grade greater than or equal to 2
• 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 \> 470 msec on the screening ECG

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

sonidegib; Paclitaxel

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Charles A Leath, III, MD, MSPH

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: July 17, 2014
• First Posted: July 21, 2014
• Study Start: September 1, 2014
• Primary Completion: December 10, 2016
• Study Completion: September 30, 2017
• Last Updated: February 9, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)