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| Sponsor: | Sanofi-Aventis |
|---|---|
| Information provided by (Responsible Party): | Sanofi-Aventis |
| ClinicalTrials.gov Identifier: | NCT01042925 |
Purpose
Phase 1 of this study will evaluate the maximum tolerated dose (MTD) of XL147 when given in combination with trastuzumab (Herceptin) and in combination with trastuzumab and paclitaxel. After the MTD is established for each combination (Phase 2), subjects will be enrolled to evaluate the preliminary efficacy and safety of these combinations in metastatic HER2 positive breast cancer. Both trastuzumab and paclitaxel are used in the treatment of metastatic breast cancer (MBC), but patients can develop resistance.
The link between PI3K mutations and trastuzumab resistance has been seen in breast cancer patients. This suggests that inhibitors of the PI3K/PTEN pathway may have the potential to restore sensitivity to trastuzumab. Similarly, introduction of activated mutant forms of PI3K has been shown to transform and confer paclitaxel resistance to immortalized breast epithelial cells. XL147 is a potent and selective inhibitor of PI3K and inhibits phosphorylation of multiple downstream components of PI3K/PTEN signaling. Therefore, XL147 may have utility in the treatment of trastuzumab resistant/refractory and HER2-positive MBC when administered in combination with trastuzumab alone or with trastuzumab and paclitaxel.
| Condition | Intervention | Phase |
|---|---|---|
|
Breast Cancer Breast Neoplasms |
Drug: XL147 (SAR245408) Biological: trastuzumab Drug: paclitaxel |
Phase I Phase II |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase 1/2 Study of XL147 (SAR245408) Administered in Combination With Trastuzumab or Paclitaxel and Trastuzumab in Subjects With Metastatic Breast Cancer Who Have Progressed on a Previous Trastuzumab-Based Regimen |
| Estimated Enrollment: | 84 |
| Study Start Date: | January 2010 |
| Estimated Study Completion Date: | January 2013 |
| Estimated Primary Completion Date: | January 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Arm 1
XL147 in combination with trastuzumab
|
Drug: XL147 (SAR245408)
administered orally once daily as tablet(s)
Biological: trastuzumab
administered by IV once every 3 weeks
Other Name: Herceptin
|
|
Experimental: Arm 2
XL147 in combination with trastuzumab and paclitaxel
|
Drug: XL147 (SAR245408)
administered orally once daily as tablet(s)
Biological: trastuzumab
administered by IV once every 3 weeks
Other Name: Herceptin
Drug: paclitaxel
administered by IV once every week
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contacts and Locations| Contact: For site information, send an email with site number to | Contact-Us@sanofi-aventis.com |
| United States, Tennessee | |
| Investigational Site Number 1214 | Recruiting |
| Nashville, Tennessee, United States, 37203 | |
| Study Director: | Clinical Sciences & Operations | Sanofi-Aventis |
More Information
| Responsible Party: | Sanofi-Aventis |
| ClinicalTrials.gov Identifier: | NCT01042925 History of Changes |
| Other Study ID Numbers: | ARD11439, XL147-203 |
| Study First Received: | January 4, 2010 |
| Last Updated: | September 12, 2011 |
| Health Authority: | United States: Food and Drug Administration; France: Afssaps - French Health Products Safety Agency; Spain: Agencia Española de Medicamentos y Productos Sanitarios |
|
HER2 positive breast cancer breast cancer breast tumors human mammary carcinoma |
|
Breast Neoplasms Neoplasms Neoplasms by Site Breast Diseases Skin Diseases Paclitaxel Trastuzumab Tubulin Modulators |
Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antineoplastic Agents, Phytogenic Antineoplastic Agents Therapeutic Uses |