Recurrent Endometrial CancerPhase 1NCT01454479
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
A Phase 1 study testing Lapatinib and ixempra in people with Recurrent Endometrial Cancer, run by Hung-Hsueh Chou.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 75 years, women only
- Conditions the study is for
- Recurrent Endometrial Cancer
- What is being tested?
- Lapatinib and ixempra
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- No sites listed yet
- Study dates
- Mar 2011to Apr 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 75 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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
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- 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
About this study
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.
Read the 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.
- Conditions
- Recurrent Endometrial Cancer
- Being tested
- Lapatinib and ixempra
- Keywords
- Lapatinib, Ixabepilone, HER-2, Endometrial Carcinoma
- Medical subject headings
- Endometrial Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lapatinib and ixempraDrug
Also called Lapatinib, Ixempra
Ixabepilone 40 mg/m2 Lapatinib 250 mg
| Study group | Role | What they receive |
|---|---|---|
| Lapatinib (Tykerb) Plus Ixabepilone | Experimental | Not described Receives: Drug: Lapatinib and ixempra |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
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.
Measured: 2013/Apr
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2011 (estimated)
- Study startMar 2011
- Primary completionApr 2013 (estimated)
- Study completionApr 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent Endometrial CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hung-Hsueh Chou
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline, Bristol-Myers Squibb
- Responsible party
- Sponsor-investigator, Hung-Hsueh Chou, Chang Gung Memorial Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01454479
- Sponsor's protocol ID
- 99-3771A3
- Status last verified
- Oct 2011
- First submitted
- 28 Sep 2011
- Last updated
- 19 Oct 2011
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01454479
- Acronym / sponsor ID
- 99-3771A3
- Conditions
- Recurrent Endometrial Cancer
- Keywords
- Lapatinib, Ixabepilone, HER-2, Endometrial Carcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Hung-Hsueh ChouUniversity, hospital or other
- Collaborators
- GlaxoSmithKline, Bristol-Myers Squibb
- Study start
- Mar 2011
- Primary completion
- Apr 2013 (estimated)
- Study completion
- Apr 2014 (estimated)
- First posted
- 19 Oct 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lapatinib (Tykerb) Plus Ixabepilone | Experimental | Drug: Lapatinib and ixempra |
Who may qualify
- Ages
- 20 to 75 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lapatinib and ixempraAlso: Lapatinib, IxempraIxabepilone 40 mg/m2 Lapatinib 250 mg | Drug | Lapatinib (Tykerb) Plus Ixabepilone |
Primary outcome
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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2011.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Lapatinib and ixempra in people with Recurrent Endometrial Cancer, run by Hung-Hsueh Chou.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 19 Oct 2011. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2011.