LDE225 and Paclitaxel in Solid Tumors

NCT01954355 | Completed Phase 1

• 4 other identifiers: SAKK 65/12CLDE225XCH01T2013DR1122SNCTP000001101
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 4

Brief Summary

The primary aim of this trial is to establish the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D) of LDE225 given in combination with standard doses of paclitaxel in patients with advanced solid tumors. In addition, the preliminary anti-tumor activity of this combination will be assessed, in particular in ovarian cancer.

Conditions

Solid Tumor; Ovarian Cancer

Keywords

advanced solid tumor; ovarian cancer; LDE225; Paclitaxel; Hedgehog inhibitor

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicities (DLTs) of the combination of LDE225 with paclitaxel in patients with advanced solid tumors

  until up to 4 weeks after start of trial therapy

Secondary Outcomes (2)

• Frequency and severity of adverse events based on the Common Terminology Criteria for Adverse Events V.4.0 (CTCAE).

  expected average 3 months

• Objective tumor responses based on RECIST 1.1 criteria.

  expected average 3 months

Study Arms (1)

LDE225 & Paclitaxel

EXPERIMENTAL

Phase I, Part A: LDE225: dose escalation in cohorts of 3-6 patients (days 1-28) and Paclitaxel 80 mg/m2 (days 1, 8, 15) Phase I, Part B and C: LDE225: RP2D established in Part A (days 1-28) and Paclitaxel 80 mg/m2 (days 1, 8, 15)

Drug: LDE225; Drug: Paclitaxel

Interventions

LDE225 DRUG

400, 600 and 800 mg OD

LDE225 & Paclitaxel

Paclitaxel DRUG

80 mg/m2 (days 1, 8, 15)

Also known as: Taxol

LDE225 & Paclitaxel

Eligibility Criteria

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

You may qualify if:

• Patient must give written informed consent before registration.
• For Part A: Histologically or cytologically confirmed diagnosis of advanced solid tumors that have progressed despite standard therapy. No more than two prior lines of chemotherapy for advanced disease.
• For Part B: Histologically or cytologically confirmed diagnosis of advanced ovarian cancer. Prior chemotherapy must have contained a platinum and a taxane at some point. Any prior taxane therapy must have been administered on a 3-week schedule. A maximum of 2 prior chemotherapy lines for advanced disease will be permitted. Patients must be refractory (PD during chemotherapy) or resistant (PD within 6 months of completing chemotherapy) to their last platinum-containing chemotherapy regimen.
• For Part C: Histologically or cytologically confirmed diagnosis of advanced ovarian cancer. Prior chemotherapy must have contained a platinum and a taxane at some point. Prior taxane therapy must have been administered on weekly schedule and must be followed by a wash-out period of at least 6 months. A maximum of 2 prior chemotherapy lines for advanced disease will be permitted. Patients must be refractory (PD during chemotherapy) or resistant (PD within 6 months of completing chemotherapy) to their last platinum-containing chemotherapy regimen.
• For Parts B and C, patients must have measurable disease according to RECIST v1.1 Radiological evaluations to be performed within 4 weeks before registration.
• WHO performance status 0-1
• Age ≥ 18 years
• Hematological values: ANC ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L, Hemoglobin ≥ 100 g/L
• Adequate hepatic function: bilirubin ≤ 1.5 x ULN, AST and ALT ≤ 2.5 x ULN or ≤ 5.0 x ULN if liver metastases are present
• Creatine phosphokinase (CPK) ≤ ULN
• Albumin ≥ 30g/L
• Adequate renal function (calculated creatinine clearance \> 50 mL/min, according to the formula of Cockcroft-Gault, see Appendix 3)
• Archived tumor tissue must be available.
• Women are not breastfeeding.
• Women of child-bearing potential are using effective contraception, are not pregnant and agree not to become pregnant during participation in the trial and during the 12 months thereafter. They are required to have a negative serum pregnancy test before registration (within 7 days).

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the trial or those who prior to the first dose of combination have not recovered to ≤ CTCAE Grade 1 from adverse events due to agents administered more than 4 weeks earlier
• Symptomatic brain metastases
• Prior therapy with a Hedgehog inhibitor
• Known or prior hypersensitivity to taxanes or drugs containing Cremophor in spite of premedication
• Positive HIV test
• Positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test
• Impairment of gastrointestinal (GI) function or GI disease (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
• Impaired cardiac function or clinically significant heart disease
• Patients who are receiving treatment with medications that are known to be strong inhibitors or inducers of CYP3A4/5 or drugs metabolized by CYP2B6 or CYP2C9 that cannot be discontinued
• Patients who are currently receiving treatment with warfarin sodium (Coumadin)
• Patients who are currently receiving immunosuppressive treatment and in whom the treatment cannot be discontinued prior to starting trial drug.
• Patients receiving medications that are recognized to cause rhabdomyolysis, such as HMG CoA reductase inhibitors (statins) clofibrate, gemfibrozil, and that cannot be stopped at least 2 weeks prior to the initiation of LDE225 treatment
• Patients who have undergone major surgery ≤ 2 weeks prior to starting trial drug or who have not recovered from such therapy
• Psychiatric disorder precluding understanding of information on trial related topics, giving informed consent, or interfering with compliance for oral drug intake.

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (4)

Istituto Oncologico della Svizzera Italiana

Bellinzona, 6500, Switzerland

Location

Kantonsspital Graubünden

Chur, 7000, Switzerland

Location

Centre Pluridisciplinaire d'Oncologie CHUV

Lausanne, 1011, Switzerland

Location

Kantonsspital St. Gallen

Sankt Gallen, 9007, Switzerland

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

• Anastasios Stathis, MD

  IOSI, Ospedale San Giovanni

  STUDY CHAIR

• Cristiana Sessa, Prof Dr med

  IOSI, Ospedale San Giovanni

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2013
• First Posted: October 1, 2013
• Study Start: September 1, 2013
• Primary Completion: October 1, 2015
• Study Completion: November 1, 2016
• Last Updated: December 6, 2019

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share

Locations

CH (4)