Clinical trial NCT00096447: Lapatinib in Treating Patients With Recurrent or Persistent Endometrial Cancer
Official title: A Phase II Evaluation Of Lapatinib (GW572016) (NCI-Supplied Agent, NSC #727989) In The Treatment Of Persistent Or Recurrent Endometrial Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Recurrent Endometrial Carcinoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: Gynecologic Oncology Group
First posted: 2004-11-10
Enrollment: 31
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase II trial is studying how well lapatinib works in treating patients with recurrent or persistent endometrial cancer. Lapatinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth

Detailed description: PRIMARY OBJECTIVES:

I. Determine the 6-month progression-free survival of patients with recurrent or persistent endometrial carcinoma treated with lapatinib.

II. Determine the nature and degree of toxicity of this drug in these patients.

SECONDARY OBJECTIVES:

I. Determine the objective response rate in patients treated with this drug. II. Determine the duration of progression-free survival and overall survival in patients treated with this drug.

III. Determine the effects of prognostic factors, such as initial performance status and tumor grade, in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive oral lapatinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 22-82 patients will be accrued for this study within 30-67 months.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed endometrial carcinoma

  * Recurrent or persistent disease
  * Histologic confirmation of the original primary tumor is required
* Refractory to curative therapy or standard treatments
* Measurable disease

  * At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques, including palpation, plain x-ray, CT scan, or MRI OR ≥ 10 mm by spiral CT scan
  * Must have at least 1 target lesion

    * Tumors within a previously irradiated field are considered non-target lesions

      * Disease in an irradiated field as the only site of measurable disease is considered a target lesion provided there has been clear progression of the lesion since the completion of prior radiotherapy
* Must have received 1 prior chemotherapy regimen for endometrial carcinoma

  * Initial therapy may have included high-dose therapy, consolidation, or extended therapy administered after surgical or non-surgical assessment
  * No more than 1 additional prior cytotoxic regimen for recurrent or persistent disease
* Tumor accessible to guided core needle or fine needle biopsy
* Ineligible for a higher priority GOG protocol (e.g., any active GOG phase III protocol for the same patient population)
* Performance status - GOG 0-2 (for patients who have received 1 prior treatment regimen)
* Performance status - GOG 0-1 (for patients who have received 2 prior treatment regimens)
* Absolute neutrophil count ≥ 1,500/mm\^3
* Platelet count ≥ 100,000/mm\^3
* Bilirubin ≤ 1.5 times upper limit of normal (ULN)
* SGOT ≤ 2.5 times ULN
* Alkaline phosphatase ≤ 2.5 times ULN
* Creatinine ≤ 1.5 times ULN
* Cardiac ejection fraction normal by echocardiogram or MUGA
* No gastrointestinal (GI) tract disease resulting in an inability to take oral medication
* No malabsorption syndrome
* No requirement for IV alimentation
* No uncontrolled inflammatory GI disease (e.g., Crohn's or ulcerative colitis)
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No active infection requiring antibiotics
* No sensory or motor neuropathy \> grade 1
* No history of allergic reaction attributed to compounds of similar chemical or biological composition to lapatinib
* No other invasive malignancy within the past 5 years except nonmelanoma skin cancer
* At least 4 weeks since prior immunologic agents for the malignant tumor
* No prior trastuzumab (Herceptin\^®) or any target-specific therapy directed to the HER family (e.g., gefitinib, erlotinib, or cetuximab)
* At least 6 weeks since prior nitrosoureas or mitomycin for the malignant tumor and recovered
* No prior non-cytotoxic chemotherapy for recurrent or persistent disease
* At least 1 week since prior hormonal therapy for the malignant tumor
* Concurrent hormone replacement therapy allowed
* Recovered from prior radiotherapy
* Recovered from prior surgery
* No prior surgery affecting absorption
* At least 4 weeks since other prior therapy for the malignant tumor
* No prior lapatinib
* No prior anticancer treatment that would preclude study treatment
* Concurrent oral anticoagulants (e.g., warfarin) allowed provided there is increased monitoring of INR
* No concurrent CYP3A4 inducers or inhibitors
* No concurrent combination antiretroviral therapy for HIV-positive patients

Primary outcomes:
measure: Percentage of Patients With Progression-free Survival > 6 Months
timeFrame: For those patients whose disease can be evaluated by physical examination, progression was assessed prior to each 28-day cycle. CT scan or MRI if used to follow lesion for measurable disease every other cycle, for up to 5 years.
measure: Frequency and Severity of Adverse Events as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) v 3.0
timeFrame: Every cycle during treatment and 30 days after the last cycle of therapy.
Secondary outcomes:
measure: Percentage of Patients With Tumor Response
timeFrame: For those patients whose disease can be evaluated by physical examination, response was assessed prior to each 28-day cycle. CT scan or MRI if used to follow lesion for measurable disease every other cycle, for up to 5 years.
measure: Duration of Progression-free Survival
timeFrame: Every other cycle during treatment, then every 3 months for the first 2 years, then every six months for the next three years and then annually for the next 5 years.
measure: Overall Survival
timeFrame: From study entry to death or last contact, up to 5 years.
measure: Prognostic Factors (Performance Status)
timeFrame: Baseline
measure: Prognostic Factor (Histologic Grade)
timeFrame: Baseline
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Gynecologic Oncology Group
state: Pennsylvania
Study officials:
affiliation: Gynecologic Oncology Group
name: Kimberly Leslie
role: PRINCIPAL_INVESTIGATOR
References: