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| ID | Type | Description | Link |
|---|---|---|---|
| XL147-001 | Other Identifier | Other study code |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental | Daily dosing for 21 days/7 days off |
|
| 2 | Experimental | Continuous daily dosing |
|
| 3 | Experimental | Continuous daily dosing |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| XL147 (SAR245408) | Drug | Gelatin capsules supplied in 25-mg and 100-mg dosage strengths |
|
| Measure | Description | Time Frame |
|---|---|---|
| Safety, tolerability, and maximum tolerated dose of oral administration of two formulations of XL147 in two treatment schedules | Assessed at each visit/periodic visits | |
| Safety and tolerability of oral dosing with XL147 capsules in subjects with lymphoma, and of XL147 capsules and tablets in subjects with solid tumors | Assessed at periodic study visits |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma pharmacokinetics of daily oral administration of XL147 in two treatment schedules | Assessed during periodic visits | |
| Pharmacodynamic effects of XL147 on tumor tissue when administered at the maximum tolerated dose in two treatment schedules | Assessed during periodic visits after MTD is determined |
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Inclusion Criteria:
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.
The subject has a histologically confirmed diagnosis of lymphoma which is relapsed or refractory to standard therapy.
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.
Subjects with indolent lymphoma must have documented disease status within 12 months prior to study entry.
The subject is ≥18 years old.
The subject's weight is ≥40 kg.
The subject has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
The subject has adequate organ and marrow function, and a fasting plasma glucose (FPG) <160 mg/dL and HbA1c of <8% at screening.
For the subjects with solid tumors who are to be enrolled into the expanded MTD cohort and tumor genetic alteration subjects:
The subject is capable of understanding and complying with the protocol and has signed the informed consent document.
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.
Female subjects of childbearing potential must have a negative serum pregnancy test at screening.
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:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Sciences & Operations | Sanofi | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Investigational Site Number 1241 | Augusta | Georgia | 30912 | United States | ||
| Investigational Site Number 1503 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29593099 | Derived | Edelman G, Rodon J, Lager J, Castell C, Jiang J, Van Allen EM, Wagle N, Lindeman NI, Sholl LM, Shapiro GI. Phase I Trial of a Tablet Formulation of Pilaralisib, a Pan-Class I PI3K Inhibitor, in Patients with Advanced Solid Tumors. Oncologist. 2018 Apr;23(4):401-e38. doi: 10.1634/theoncologist.2017-0691. Epub 2018 Mar 28. |
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| ID | Term |
|---|---|
| D009369 | Neoplasms |
| D008223 | Lymphoma |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| C581157 | XL147 |
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| XL147 (SAR245408) | Drug | Tablets supplied as 100-mg, 150-mg, and 200-mg dosage strengths |
|
| Plasma pharmacokinetics of XL147 capsule and tablet formulations | Assessed during periodic visits after the preliminary MTD for the continuous daily dosing schedule is determined |
| Boston |
| Massachusetts |
| 02115 |
| United States |
| Investigational Site Number 1401 | Dallas | Texas | 75230 | United States |
| Investigational Site Number 3412 | Barcelona | 08035 | Spain |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |