ClinicalTrials.gov
ClinicalTrials.gov Menu

LDE225 and Paclitaxel in Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01954355
Recruitment Status : Completed
First Posted : October 1, 2013
Last Update Posted : November 25, 2016
Sponsor:
Information provided by (Responsible Party):
Swiss Group for Clinical Cancer Research

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.

Condition or disease Intervention/treatment Phase
Solid Tumor Ovarian Cancer Drug: LDE225 Drug: Paclitaxel Phase 1

Detailed Description:

This is a multicenter, open label phase I dose-escalation trial of LDE225 administered once daily (OD) with Paclitaxel administered weekly for three weeks (days 1, 8, 15) in 28-day cycles in adult patients with advanced solid tumors that have progressed despite standard therapy.

The trial will consist of three parts. In Part A (dose escalation following a standard 3+3 design), patients with previously treated advanced solid tumors will receive escalating doses of LDE225 in combination with standard Paclitaxel doses, to define the MTD and the RP2D of LED225 OD that can be given in combination with standard doses of Paclitaxel. Once the MTD and RP2D is established in 6 patients, then part B will start.

Part B and C are expansion cohorts in patients with advanced platinum-resistant ovarian cancer (6 patients each) to further evaluate the safety of the combination and to assess for any preliminary antitumor activity.

In Part B, any prior taxane therapy must have been administered on a 3-week schedule. In Part C, prior taxane therapy must have been administered on weekly schedule and has to be followed by a wash-out period of at least 6 months.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: LDE225 in Combination With Paclitaxel in Patients With Advanced Solid Tumors - A Multicenter Phase I Trial
Study Start Date : September 2013
Actual Primary Completion Date : October 2015
Actual Study Completion Date : November 2016


Arm Intervention/treatment
Experimental: LDE225 & Paclitaxel

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
400, 600 and 800 mg OD

Drug: Paclitaxel
80 mg/m2 (days 1, 8, 15)
Other Name: Taxol




Primary Outcome Measures :
  1. Dose limiting toxicities (DLTs) of the combination of LDE225 with paclitaxel in patients with advanced solid tumors [ Time Frame: until up to 4 weeks after start of trial therapy ]

Secondary Outcome Measures :
  1. Frequency and severity of adverse events based on the Common Terminology Criteria for Adverse Events V.4.0 (CTCAE). [ Time Frame: expected average 3 months ]
  2. Objective tumor responses based on RECIST 1.1 criteria. [ Time Frame: expected average 3 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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).
  • Men agree not to father a child during participation in the trial and during 12 months thereafter. They agree to use effective contraception.

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01954355


Locations
Switzerland
Istituto Oncologico della Svizzera Italiana
Bellinzona, Switzerland, 6500
Kantonsspital Graubünden
Chur, Switzerland, 7000
Centre Pluridisciplinaire d`Oncologie CHUV
Lausanne, Switzerland, 1011
Kantonsspital St. Gallen
St. Gallen, Switzerland, 9007
Sponsors and Collaborators
Swiss Group for Clinical Cancer Research
Investigators
Study Chair: Anastasios Stathis, MD IOSI, Ospedale San Giovanni
Study Chair: Cristiana Sessa, Prof Dr med IOSI, Ospedale San Giovanni

Responsible Party: Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier: NCT01954355     History of Changes
Other Study ID Numbers: SAKK 65/12
CLDE225XCH01T ( Other Identifier: Novartis )
2013DR1122 ( Other Identifier: Swissmedic )
SNCTP000001101 ( Other Identifier: SNCTP )
First Posted: October 1, 2013    Key Record Dates
Last Update Posted: November 25, 2016
Last Verified: November 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Swiss Group for Clinical Cancer Research:
advanced solid tumor
ovarian cancer
LDE225
Paclitaxel
Hedgehog inhibitor

Additional relevant MeSH terms:
Ovarian Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Paclitaxel
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action