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A Trial of LEE011 in Patients With Advanced Solid Tumors or Lymphoma.

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: NCT01237236
Recruitment Status : Completed
First Posted : November 9, 2010
Last Update Posted : August 23, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE November 5, 2010
First Posted Date  ICMJE November 9, 2010
Last Update Posted Date August 23, 2018
Actual Study Start Date  ICMJE December 21, 2010
Actual Primary Completion Date March 9, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 8, 2010)
Primary Outcome Measures: Maximum tolerated dose of LEE011 when administered orally once daily, as assessed by Frequency of DLTs as a function of LEE011 dose [ Time Frame: 12 month ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01237236 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 13, 2013)
  • Safety and tolerability of LEE011, as assessed by grade and frequency of Adverse events, serious adverse events, and changes in lab values, vital signs and ECGs. [ Time Frame: 18 months ]
  • The pharmacokinetics (PK) of LEE011 (AUC inf, Cmax, Tmax, T1/2) [ Time Frame: 18 months ]
  • Any pharmacodynamic activity of LEE011 treatment, as assessed by changes from baseline in biomarkers associated with the pharmacologic activity of LEE011 [ Time Frame: 18 months ]
  • Antitumor activity that may be associated with LEE011 treatment, as assessed by CT/MRI Response Evaluation Criteria for Solid Tumors (RECIST) Criteria v1.0 or Cheson Criteria 2007 for lymphomas. [ Time Frame: 18 months ]
  • Relationship between QTc prolongation and exposure to LEE011 and/or any of its relevant metabolites. [ Time Frame: 18 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: November 8, 2010)
  • Safety and tolerability of LEE011, as assessed by grade and frequency of Adverse events, serious adverse events, and changes in lab values, vital signs and ECGs. [ Time Frame: 18 months ]
  • The pharmacokinetics (PK) of LEE011 (AUC inf, Cmax, Tmax, T1/2) [ Time Frame: 18 months ]
  • Any pharmacodynamic activity of LEE011 treatment, as assessed by changes from baseline in biomarkers associated with the pharmacologic activity of LEE011 [ Time Frame: 18 months ]
  • Antitumor activity that may be associated with LEE011 treatment, as assessed by CT/MRI Response Evaluation Criteria for Solid Tumors (RECIST) Criteria v1.0 or Cheson Criteria 2007 for lymphomas. [ Time Frame: 18 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Trial of LEE011 in Patients With Advanced Solid Tumors or Lymphoma.
Official Title  ICMJE A phase1 Multi-center, Open Label, Dose-escalation Study of Oral LEE011 in Patients With Advanced Solid Tumors or Lymphoma
Brief Summary

LEE011 is a new oral drug designed to inhibit the activity of an enzyme known as CDK4/6. CDK4/6 is involved in the process that allows both normal and cancer cells to divide and multiply. Cancer cells are often driven to divide and multiply by abnormalities that increase the activity of CDK4. Hence there is hope that blocking the activity of CDK4 may slow the growth of some cancers. LEE011 has shown anti-cancer activity in several different tumor models in animals.

Because CDK4 is important in both normal and cancerous cells, LEE011 is expected to decrease the ability of the bone marrow to make white blood cells, platelets, and red blood cells. Although these effects are expected to be reversible, they can increase the risk of infection, bleeding and fatigue.

The primary purpose of this study is to find the highest dose of LEE011 that can be safely given to adult patients with advanced solid tumors or lymphomas for which no further effective standard treatment is available. It will provide information about the side effects that may occur following treatment. The study will also possibly provide early evidence for LEE011's anti-tumor activity.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Advanced Solid Tumor
  • Lymphomas
Intervention  ICMJE Drug: LEE011
Study Arms  ICMJE Experimental: LEE011
Intervention: Drug: LEE011
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 9, 2017)
156
Original Estimated Enrollment  ICMJE
 (submitted: November 8, 2010)
60
Actual Study Completion Date  ICMJE March 9, 2017
Actual Primary Completion Date March 9, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Patients aged ≥18 years with a histologically or cytologically confirmed diagnosis of a solid tumor or lymphoma for which no further effective standard treatment is available
  2. Patients must have an ECOG performance status of 0 - 1
  3. Patients enrolled in the dose expansion phase must have at least one measurable lesion as defined by RECIST criteria for solid tumors or Measurable nodal disease at baseline as defined by Cheson criteria for Lymphoma.
  4. A sufficient interval must have elapsed between the last dose of prior anti-cancer therapy (including cytotoxic and biological therapies and major surgery) and enrollment in this study, to allow the effects of prior therapy to have abated:

    • Cytotoxic chemotherapy: ≥ the duration of the cycle of the most recent treatment regimen (a minimum of 2 weeks for all regimens, except 6 weeks for nitrosoureas and mitomycin-C).
    • Biologic therapy (e.g., antibodies): ≥ 4 weeks.
  5. Patients must have adequate organ function, as defined by the following parameters:

    • Bone marrow: Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L, Hemoglobin (Hgb) ≥ 9 g/dL, Platelets ≥ 100 x 109/L
    • Hepatic function: Serum total bilirubin ≤ 1.5 x ULN (upper limit of normal); AST (SGOT) and ALT (SGPT) ≤ 3 x ULN, except in patients with tumor involvement of the liver who must have AST and ALT ≤ 5 x ULN
    • Renal function: Serum creatinine ≤ 1.5 x ULN or 24-hour clearance ≥ 40 ml/min, Serum potassium, magnesium and calcium must be within normal limits

Exclusion Criteria:

  1. Patients with primary central nervous system tumors or brain metastases. However, if radiation therapy and/or surgery has been completed and serial evaluation by CT (with contrast enhancement) or MRI over a minimum of 3 months demonstrates the disease to be stable and if the patient remains asymptomatic, then the patient may be enrolled. Such patients must have no need for treatment with steroids or anti-epileptic medications.
  2. Impairment of gastro-intestinal (GI) function or GI disease that may significantly alter the absorption of LEE011 such as patients with a history of GI surgery which may result in intestinal blind loops and patients with clinically significant gastroparesis, unresolved nausea, vomiting, or diarrhea of CTCAE grade > 1
  3. Prior hematopoietic stem cell or bone marrow transplantation
  4. Impaired cardiac function or clinically significant cardiac diseases, including any of the following:

    • LVEF <45% as determined by MUGA or echo
    • Complete left bundle branch block
    • Obligate use of a cardiac pacemaker or implantable cardioverter defibrillator
    • Congenital long QT syndrome or family history of unexpected sudden cardiac death
    • History or presence of ventricular tachyarrhythmia
    • Presence of unstable atrial fibrillation (ventricular response > 100 bpm
    • Clinically significant resting bradycardia
    • QTcF >450 ms for males and >470 ms for females on screening ECG
    • Right bundle branch block and left anterior hemiblock (bifascicular block)
    • Angina pectoris ≤ 3 months prior to dosing with study drug
    • Acute MI ≤ 3 months prior to dosing with study drug
    • Other clinically significant heart disease
  5. Acute myocardial infarction or angina pectoris ≤ 3 months prior to starting study drug
  6. Patients with concurrent severe and/or uncontrolled concurrent medical conditions that could compromise participation in the study (e.g. uncontrolled hypertension and/or diabetes mellitus, clinically significant pulmonary disease, clinically significant neurological disorder, active or uncontrolled infection).

Known diagnosis of HIV or hepatitis C

Other protocol-defined inclusion/exclusion criteria may apply

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   Netherlands,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01237236
Other Study ID Numbers  ICMJE CLEE011X2101
2009-017017-30 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP