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Study of the Safety and Pharmacokinetics of XL147 (SAR245408) in Adults With 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. Identifier: NCT00486135
Recruitment Status : Completed
First Posted : June 13, 2007
Last Update Posted : February 1, 2013
Information provided by (Responsible Party):

Brief Summary:
The purpose of this study is to evaluate the safety and tolerability of XL147 in subjects with solid tumors or lymphoma. Both a capsule and a tablet formulation will be evaluated. XL147 is a new chemical entity that inhibits PI3 Kinase. Inactivation of PI3K has been shown to inhibit growth and induce apoptosis (programmed cell death) in tumor cells.

Condition or disease Intervention/treatment Phase
Cancer Lymphoma Drug: XL147 (SAR245408) Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 118 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Dose-Escalation Study of the Safety and Pharmacokinetics of XL147 Administered Orally Daily to Subjects With Solid Tumors or Lymphoma
Study Start Date : June 2007
Actual Primary Completion Date : October 2012
Actual Study Completion Date : October 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: 1
Daily dosing for 21 days/7 days off
Drug: XL147 (SAR245408)
Gelatin capsules supplied in 25-mg and 100-mg dosage strengths

Experimental: 2
Continuous daily dosing
Drug: XL147 (SAR245408)
Gelatin capsules supplied in 25-mg and 100-mg dosage strengths

Experimental: 3
Continuous daily dosing
Drug: XL147 (SAR245408)
Tablets supplied as 100-mg, 150-mg, and 200-mg dosage strengths

Primary Outcome Measures :
  1. Safety, tolerability, and maximum tolerated dose of oral administration of two formulations of XL147 in two treatment schedules [ Time Frame: Assessed at each visit/periodic visits ]
  2. Safety and tolerability of oral dosing with XL147 capsules in subjects with lymphoma, and of XL147 capsules and tablets in subjects with solid tumors [ Time Frame: Assessed at periodic study visits ]

Secondary Outcome Measures :
  1. Plasma pharmacokinetics of daily oral administration of XL147 in two treatment schedules [ Time Frame: Assessed during periodic visits ]
  2. Pharmacodynamic effects of XL147 on tumor tissue when administered at the maximum tolerated dose in two treatment schedules [ Time Frame: Assessed during periodic visits after MTD is determined ]
  3. Plasma pharmacokinetics of XL147 capsule and tablet formulations [ Time Frame: Assessed during periodic visits after the preliminary MTD for the continuous daily dosing schedule is determined ]

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.

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

Inclusion Criteria:

  1. The subject has a histologically confirmed solid tumor that is metastatic or unresectable, and for which standard curative or palliative measures do not exist or are no longer effective, and there are no known therapies to prolong survival. An expanded cohort will be enrolled; NSCLC subjects enrolled must have a diagnosis of relapsed or refractory NSCLC (Stage IIIB or IV) and have received at least two prior regimens including one platinum-based chemotherapy regimen.
  2. The subject has a histologically confirmed diagnosis of lymphoma which is relapsed or refractory to standard therapy.
  3. For subjects with solid tumors, the subject has disease that is assessable by tumor marker, physical, or radiologic means. There are separate criteria that apply to subjects with lymphoma.
  4. Subjects with indolent lymphoma must have documented disease status within 12 months prior to study entry.
  5. The subject is ≥18 years old.
  6. The subject's weight is ≥40 kg.
  7. The subject has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
  8. The subject has adequate organ and marrow function, and a fasting plasma glucose (FPG) <160 mg/dL and HbA1c of <8% at screening.
  9. For the subjects with solid tumors who are to be enrolled into the expanded MTD cohort and tumor genetic alteration subjects:

    1. tumor tissue amenable to serial biopsy, and
    2. additional informed consent.
  10. The subject is capable of understanding and complying with the protocol and has signed the informed consent document.
  11. Sexually active subjects (male and female) must use medically acceptable methods of contraception during the course of the study and for 3 months following discontinuation of study drug.
  12. Female subjects of childbearing potential must have a negative serum pregnancy test at screening.
  13. At least ten 4-10 micron tissue sections, archival or fresh, or a tissue block, of the subject's tumor should be identified and designated for shipment to the sponsor where allowed by local regulatory bodies. For subjects with lymphoma, tissue from an excisional or core biopsy or, in case of marrow involvement, a bone marrow aspirate/biopsy is acceptable.

Exclusion Criteria:

  1. The subject has previously been treated with a selective PI3K inhibitor.
  2. Additional restrictions on prior treatment apply.
  3. For lymphoma subjects: known central nervous system involvement, autoimmune disease requiring immunosuppressive therapy, systemic treatment with prednisone >20mg/day or equivalent within 2 weeks prior to first dose of XL147, autologous stem cell transplantation within 12 weeks prior to first dose, history of any allogeneic transplantation.
  4. The subject has not recovered from toxicity due to all prior therapies.
  5. The subject has a primary brain tumor. Subjects with brain metastasis are considered eligible if the subject has not received radiation therapy for brain metastasis within 2 weeks of enrollment and has been on a stable dose of steroids for 2 or more weeks.
  6. The subject is currently receiving anticoagulation with therapeutic doses of warfarin (low-dose warfarin is permitted).
  7. The subject has prothrombin time/partial thromboplastin time (PT/PTT) or International Normalized Ratio (INR) test results at screening that are above 1.3x the laboratory upper limit of normal.
  8. The subject has an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
  9. The subject has psychiatric illness/social situation(s) that would limit compliance with study requirements.
  10. The subject is pregnant or breastfeeding.
  11. The subject is known to be positive for the human immunodeficiency virus (HIV).
  12. The subject has a previously identified allergy or hypersensitivity to components of the XL147 formulation.
  13. The subject has a baseline corrected QT interval (QTc) >460 ms.
  14. The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee.

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 identifier (NCT number): NCT00486135

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United States, Georgia
Investigational Site Number 1241
Augusta, Georgia, United States, 30912
United States, Massachusetts
Investigational Site Number 1503
Boston, Massachusetts, United States, 02115
United States, Texas
Investigational Site Number 1401
Dallas, Texas, United States, 75230
Investigational Site Number 3412
Barcelona, Spain, 08035
Sponsors and Collaborators
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Study Director: Clinical Sciences & Operations Sanofi
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Sanofi Identifier: NCT00486135    
Other Study ID Numbers: TED11433
XL147-001 ( Other Identifier: Other study code )
First Posted: June 13, 2007    Key Record Dates
Last Update Posted: February 1, 2013
Last Verified: January 2013
Keywords provided by Sanofi:
Solid tumors
Additional relevant MeSH terms:
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Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases