Lapatinib in Treating Patients With Persistent or Recurrent Ovarian Epithelial or Peritoneal Cancer

Phase 2

Completed

• Conditions: Primary Peritoneal Cavity Cancer; Recurrent Ovarian Epithelial Cancer
• Interventions: Drug: lapatinib ditosylate; Other: laboratory biomarker analysis

• Registration Number: NCT00113373
• Lead Sponsor: National Cancer Institute (NCI)

Brief Summary

Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. This phase II trial is studying how well lapatinib works in treating patients with persistent or recurrent ovarian epithelial or peritoneal cancer.

Detailed Description

OBJECTIVES: Primary I. Determine 6-month progression-free survival of patients with persistent or recurrent ovarian epithelial or primary peritoneal cancer treated with lapatinib.

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

Secondary I. Determine the clinical response rate (partial and complete response) in patients treated with this drug.

II. Determine the duration of progression-free and overall survival of patients treated with this drug.

III. Determine the impact of prognostic variables, including platinum sensitivity, performance status, and cellular histology (clear cell or mucinous type), on patients treated with this drug.

IV. Correlate tumor levels of expression of epidermal growth factor receptors (EGFR), phosphorylated EGFR, HER2/neu, and Ki-67, as determined by immunohistochemistry, with clinical response in patients treated with this drug.

V. Correlate EGFR mutations in tumor DNA with clinical response 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.

After completion of study therapy, patients are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 22-60 patients will be accrued for this study within 12-26 months.

Study Timeline

• Study Start: 2005-05
• Study First Submitted: 2005-06-07
• Study First Submitted QC: 2005-06-07
• Study First Posted: 2005-06-08
• Primary Completion: 2011-03
• Study Completion: 2011-03
• Results First Submitted: 2015-05-28
• Results First Submitted QC: 2015-05-28
• Results First Posted: 2015-06-11
• Status Verified: 2019-07
• Last Update Submitted: 2019-07-22
• Last Update Posted: 2019-07-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 28

Inclusion Criteria

• Histologically confirmed persistent or recurrent ovarian epithelial or primary peritoneal cancer

• Measurable disease

  • At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan

  • Presence of ≥ 1 target lesion

    • Tumors within a previously irradiated field are not considered target lesions unless evidence of progression is documented or proven by biopsy 3 months after completion of radiotherapy

• Disease progression during OR persistent disease after 1 prior platinum-based chemotherapy regimen* for primary disease containing carboplatin, cisplatin, or another organoplatinum compound

  • Initial treatment may have included high-dose therapy, consolidation therapy, or extended therapy administered after surgical or non-surgical assessment
  • Treatment-free interval after platinum-based chemotherapy < 12 months

• Tumor accessible by guided core needle or fine needle biopsy

• Ineligible for any higher priority Gynecologic Oncology Group (GOG) protocols (i.e., any active phase III protocol for the same patient population)

• Performance status - GOG 0-2 (patients who have received 1 prior treatment regimen)

• Performance status - GOG 0-1 (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)

• Serum Glutamate Oxaloacetate Transaminase (SGOT) ≤ 2.5 times ULN

• Alkaline phosphatase ≤ 2.5 times ULN

• Creatinine ≤ 1.5 times ULN

• Ejection fraction normal by echocardiogram or MUGA

• No GI 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 disease or ulcerative colitis)

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for ≥ 1 month after completion of study treatment

• No active infection requiring antibiotics

• No sensory or motor neuropathy > grade 1

• No other invasive malignancy within the past 5 years except nonmelanoma skin cancer

• No history of allergic reaction attributed to compounds of similar chemical or biological composition to lapatinib

• At least 4 weeks since prior immunologic agents for the malignancy

• No prior trastuzumab (Herceptin®)or cetuximab

• See Disease Characteristics

• Recovered from prior chemotherapy

• At least 6 weeks since prior nitrosoureas or mitomycin for the malignancy

• No prior non-cytotoxic chemotherapy for recurrent or persistent disease

• At least 2 weeks since prior and no concurrent dexamethasone or dexamethasone equivalent dose > 1.5 mg/day

• At least 1 week since prior hormonal therapy for the malignancy

• Concurrent hormone replacement therapy allowed

• See Disease Characteristics

• Recovered from prior radiotherapy

• No prior radiotherapy to > 25% of marrow-bearing areas

• See Disease Characteristics

• Recovered from prior surgery

• No prior surgical procedure affecting gastrointestinal (GI) absorption

• At least 4 weeks since other prior therapy for the malignancy

• At least 6 months since prior and no concurrent amiodarone

• At least 1 week since other prior and no concurrent CYP3A4 inhibitors

• At least 2 weeks since prior and no concurrent CYP3A4 inducers

• At least 1 week since prior and no concurrent H2 inhibitors or proton pump inhibitors

  • Concurrent antacids allowed provided they are not administered within 1 hour before and 1 hour after study drug administration

• No prior cancer treatment that would preclude study treatment

• No prior lapatinib

• No other prior target-specific therapy directed to the HER family (e.g., gefitinib or erlotinib)

• No concurrent herbal medications

• No concurrent combination antiretroviral therapy for HIV-positive patients

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (lapatinib ditosylate)	lapatinib ditosylate	Patients receive oral lapatinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Treatment (lapatinib ditosylate)	laboratory biomarker analysis	Patients receive oral lapatinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Progression-free Survival (PFS) > 6 Months	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 measurable disease every other cycle for the first 6 months	Progression is defined according to RECIST v1.0 as at least a 20% increase in the sum of LD target lesions taking as reference the smallest sum LD recorded since study entry, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression, or unequivocal progression of existing non-target lesions.
Frequency and Severity of Adverse Effects as Assessed by Common Toxicity Criteria for Adverse Events (CTCAE) v3.0	Assessed every cycle while on treatment, 30 days after the last cycle of treatment

Secondary Outcome Measures

Name	Time	Method
Tumor Response	Baseline, every other cycle for 6 months and then every 6 months for up to 5 years	RECIST 1.0 defines complete response as the disappearance of all target lesions and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Partial response is defined as at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD. There can be no unequivocal progression of non-target lesions and no new lesions. Documentation by two disease assessments at least 4 weeks apart is required. In the case where the ONLY target lesion is a solitary pelvic mass measured by physical exam, which is not radiographically measurable, a 50% decrease in the LD is required. These patients will have their response classified according to the definitions stated above. Complete and partial responses are included in the objective tumor response rate.
Overall Survival	From entry into the study to death or the date of last contact, assessed up to 5 years	The observed length of life from entry into the study to death or the date of last contact.
Prognostic Variable: Platinum Sensitivity	Baseline	Patients who had disease progression within 6 months of ending their last regimen of platinum therapy were considered platinum resistant. Patients who had disease progression between 6 and 12 months of ending their last platinum regimen were considered platinum sensitive. Patients who had disease progression beyond12 months of ending their last platinum regimen were also considered platinum sensitive.
Duration of Progression-free Survival	Every other cycle for 6 months and then every 6 months for up to 5 years.	Progression is defined according to RECIST v1.0 as at least a 20% increase in the sum of LD target lesions taking as reference the smallest sum LD recorded since study entry, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression, or unequivocal progression of existing non-target lesions.
Prognostic Variable: Cellular Histology	Baseline	Number of patients with Clear Cell Carcinoma or Mucinous Carcinoma
Prognostic Variables: Performance Status	Baseline	Performance Status 0 = Fully active, able to carry on all pre-disease performance without restriction Performance Status 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of light or sedentary nature, e.g., light housework, office work Performance Status 2 = Ambulatory and capable of all self care but unable to carry out any work activities. Up and about more than 50% of waking hours.

Trial Locations

Locations (1)

Gynecologic Oncology Group; 🇺🇸 Philadelphia, Pennsylvania, United States