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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

Primary Purpose

Recurrent Endometrial Cancer

Status

Unknown status

Phase

Phase 1

Locations

Study Type

Interventional

Intervention

Lapatinib and ixempra

About this trial

This is an interventional treatment trial for Recurrent Endometrial Cancer focused on measuring Lapatinib, Ixabepilone, HER-2, Endometrial Carcinoma

Eligibility Criteria

20 Years - 75 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

Histologically confirmed carcinoma or carcinosarcoma of the endometrium with evidence of persistent disease or progression after initial surgery and adjuvant chemotherapy, radiotherapy, or both, not amenable for curative salvage therapy.
ErbB2 gene amplification by FISH (ErbB2 gene copies to chromosome 17 signals) of > = 2.0; ErbB2 overexpression is defined by immunostaining >=2 for ErB2
Measurable disease, defined as ≥1 lesions that can be accurately measured in
- 1 dimensions as ≥20 mm by conventional techniques OR as ≥10 mm by spiral CT scan, MRI or PET scan (those who undergo cytoreductive salvage surgery with residual tumor ≥ 20 mm are eligible)
Those who are chemotherapy-naive be enrolled until failing one chemotherapy regimen
Prior treatments with radiation therapy for palliative management of metastatic disease is permitted provided that at least 4 weeks have elapsed since the last fraction of radiation therapy, disease progression has been documented and all treatment related adverse events are ≦ grade 2 at the time of registration.
Life expectancy ≥ 12 weeks
ECOG(Eastern Cooperative Oncology Group) performance status 0-2
Patients must have normal organ and marrow function measured within 14 days

Exclusion Criteria:

Previously unirradiated, isolated vaginal, pelvic or paraaortic lymph node, lung (which confined to one lobe that can be resected or radiated) recurrence or other potentially curable recurrence such as central pelvic recurrence for which a pelvic exenteration is feasible
Pregnant or lactating women.
Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
Prior therapy with Lapatinib or Ixabepilone.
CNS metastases.
Ongoing other concurrent investigational agents or anticancer therapy
Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, serious non- healing wound/ulcer/bone fracture, or psychiatric illness/social situations that would limit compliance with study requirements.
Patients with GI tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis).
Preexisting peripheral neuropathy≥G2

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Lapatinib (Tykerb) Plus Ixabepilone

Arm Description

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

NCT ID

NCT01454479

First Posted

September 28, 2011

Last Updated

October 18, 2011

Sponsor

Hung-Hsueh Chou

Collaborators

GlaxoSmithKline, Bristol-Myers Squibb

1. Study Identification

Unique Protocol Identification Number

NCT01454479

Brief 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

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 Type

Interventional

2. Study Status

Record Verification Date

October 2011

Overall Recruitment Status

Unknown status

Study Start Date

March 2011 (undefined)

Primary Completion Date

April 2013 (Anticipated)

Study Completion Date

April 2014 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Hung-Hsueh Chou

Collaborators

GlaxoSmithKline, Bristol-Myers Squibb

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

Detailed Description

Patients receive weekly Ixabepilone 32 mg/m2 (D1) and a 4-level of oral Lapatinib 500-1250 mg once daily continuously. The recommended duration of treatment for each patient 21 days a cycle of total 6 cycles or until disease progression, or unacceptable toxicity or patient's refusal occurred.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Recurrent Endometrial Cancer

Keywords

Lapatinib, Ixabepilone, HER-2, Endometrial Carcinoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Lapatinib (Tykerb) Plus Ixabepilone

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

Lapatinib and ixempra

Other Intervention Name(s)

Lapatinib, Ixempra

Intervention Description

Ixabepilone 40 mg/m2 Lapatinib 250 mg

Primary Outcome Measure Information:

Title

Description

Time Frame

2013/Apr

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Histologically confirmed carcinoma or carcinosarcoma of the endometrium with evidence of persistent disease or progression after initial surgery and adjuvant chemotherapy, radiotherapy, or both, not amenable for curative salvage therapy. ErbB2 gene amplification by FISH (ErbB2 gene copies to chromosome 17 signals) of > = 2.0; ErbB2 overexpression is defined by immunostaining >=2 for ErB2 Measurable disease, defined as ≥1 lesions that can be accurately measured in 1 dimensions as ≥20 mm by conventional techniques OR as ≥10 mm by spiral CT scan, MRI or PET scan (those who undergo cytoreductive salvage surgery with residual tumor ≥ 20 mm are eligible) Those who are chemotherapy-naive be enrolled until failing one chemotherapy regimen Prior treatments with radiation therapy for palliative management of metastatic disease is permitted provided that at least 4 weeks have elapsed since the last fraction of radiation therapy, disease progression has been documented and all treatment related adverse events are ≦ grade 2 at the time of registration. Life expectancy ≥ 12 weeks ECOG(Eastern Cooperative Oncology Group) performance status 0-2 Patients must have normal organ and marrow function measured within 14 days Exclusion Criteria: Previously unirradiated, isolated vaginal, pelvic or paraaortic lymph node, lung (which confined to one lobe that can be resected or radiated) recurrence or other potentially curable recurrence such as central pelvic recurrence for which a pelvic exenteration is feasible Pregnant or lactating women. Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment) Prior therapy with Lapatinib or Ixabepilone. CNS metastases. Ongoing other concurrent investigational agents or anticancer therapy Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, serious non- healing wound/ulcer/bone fracture, or psychiatric illness/social situations that would limit compliance with study requirements. Patients with GI tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis). Preexisting peripheral neuropathy≥G2

12. IPD Sharing Statement

Learn more about this trial

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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