A Phase I Study of Lapatinib (Tykerb) Plus Ixabepilone (Ixempra) as 2nd-line Treatment for Patients With HER-2 Overexpressed Recurrent or Persistent Endometrial Carcinoma or Carcinosarcoma
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|ClinicalTrials.gov Identifier: NCT01454479|
Recruitment Status : Unknown
Verified October 2011 by Hung-Hsueh Chou, Chang Gung Memorial Hospital.
Recruitment status was: Enrolling by invitation
First Posted : October 19, 2011
Last Update Posted : October 19, 2011
Endometrial cancer (EC) is the 8th most common female cancer in Taiwan. Its incidence is increasing in the recent few years, around 1,200 new cases per year. The outcome of recurrent EC is disappointing, except focal recurrences that could be irradiated or removed. Chemotherapy is currently the most common salvage treatment for recurrent endometrial cancer. However, the response rate (RR) to 2nd-line treatment is approximately 0-27.3%, with short median time to progression, 2-3.9 months and low overall survival, 6.4-11 months.
Due to progress of studies on the molecular and genetic basis of cancer and cellular signaling pathways, targeted therapy has been developed for various cancer treatments. A Gynecologic Oncology Group study found 44% of advanced endometrial cancer had HER>=2+ and the ratio of HER2:chromosome 17 (CEP17) >=2. Another study showed that HER>=2+ was seen in 47% of carcinosarcoma. These evidences indicated HER2 gene amplification and HER2 overexpression occur in endometrial cancer and carcinosarcoma, especially in those of high grade and recurrence. Lapatinib (L), an oral inhibitor of both EGFR(epidermal growth factor receptor) and HER2(human epidermal growth receptor), has been shown to be an effective treatment in HER2/neu overexpressing metastatic breast cancer. Ixabepilone is a semisynthetic analog of the natural product epothilone B, and recently has been approved by US Food and Drug Administration as a treatment option in metastatic breast cancer. It was also observed that lapatinib + ixabepilone killed more breast tumor cells than trastuzumab + paclitaxel in vitro. Two GOG(Gynecologic Oncology Group) studies had reported that weekly Ixabepilone as 2nd-line chemotherapy provided a similar RR to 3-weekly regimen of 14.3% in platinum- and taxane-resistant epithelial ovarian cancer with less severe toxicities. The combination of lapatinib and ixabepilone is expected to become an effective treatment for recurrent endometrial cancer and carcinosarcoma, but the ideal dose is yet to be surveyed.
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Endometrial Cancer||Drug: Lapatinib and ixempra||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Study of Lapatinib (Tykerb) Plus Ixabepilone (Ixempra) as 2nd-line Treatment for Patients With HER-2 Overexpressed Recurrent or Persistent Endometrial Carcinoma or Carcinosarcoma|
|Study Start Date :||March 2011|
|Estimated Primary Completion Date :||April 2013|
|Estimated Study Completion Date :||April 2014|
|Experimental: Lapatinib (Tykerb) Plus Ixabepilone||
Drug: Lapatinib and ixempra
Ixabepilone 40 mg/m2 Lapatinib 250 mg
- Determine the Maximum Tolerated Dosage (MTD) of the combination of lapatinib with Ixabepilone as 2nd-line chemotherapy in patients with treatment in HER2 overexpressed recurrent or persistent endometrial cancer or carcinosarcoma [ Time Frame: 2013/Apr ]Determine the Maximum Tolerated Dosage (MTD) of the combination of lapatinib with Ixabepilone as 2nd-line chemotherapy in patients with treatment in HER2 overexpressed recurrent or persistent endometrial cancer or carcinosarcoma.