Erlotinib and Carboplatin in Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

OBJECTIVES:

• Determine the response rate in patients with recurrent ovarian epithelial, fallopian tube, or primary peritoneal cancer treated with erlotinib and carboplatin.
• Determine the duration of stable disease, time to progression, and response duration in patients treated with this regimen.
• Determine the toxicity of this regimen in these patients.
• Correlate the level of epidermal growth factor receptor tumor expression with objective tumor response in patients treated with this regimen.

OUTLINE: This is a multicenter study. Patients are stratified according to response to prior platinum-containing therapy (platinum-sensitive, defined as 6 months or more since prior therapy with platinum agent [closed to accrual as of 2/13/2004], vs platinum-resistant, defined as less than 6 months since prior therapy with platinum agent).

Patients receive carboplatin IV over 30 minutes on day 1 and oral erlotinib once daily on days 1-21. Treatment repeats every 21 days for up to 6 courses. After the completion of 6 courses of therapy, patients with responsive or stable disease may continue to receive erlotinib and carboplatin in the absence of disease progression or unacceptable toxicity.

Patients are followed at 4 weeks and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 23-60 patients (8-30 for platinum-sensitive stratum [closed to accrual as of 2/13/2004] and 15-30 for platinum-resistant stratum) will be accrued for this study within 15-23 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed recurrent ovarian epithelial, fallopian tube, or primary peritoneal cancer for which no standard curative therapy exists
• At least 1 measurable lesion

• At least 20 mm by x-ray, non-spiral CT scan, or physical exam OR at least 10 mm by spiral CT scan
• Ascites and bone metastases not considered measurable disease
• No abdominal adenocarcinoma of unknown origin or borderline ovarian tumor
• No elevated CA 125 as only evidence of disease
• At least 1 but no more than 2 prior chemotherapy regimens required

• First regimen must have contained cisplatin or carboplatin
• Switching platinum compounds due to disease progression or failure to respond is considered 2 regimens
• Same regimen as first- and second-line therapy is considered 2 regimens
• Responded to prior platinum-based first-line chemotherapy

• No platinum-refractory disease
• No known brain metastases

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 12 weeks

Hematopoietic:

• Absolute granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than upper limit of normal (ULN)
• AST/ALT no greater than 2.5 times ULN

Renal:

• Creatinine no greater than ULN

Cardiovascular:

• No symptomatic congestive heart failure
• No unstable angina
• No cardiac arrhythmia

Gastrointestinal:

• See Surgery
• No GI tract disease resulting in an inability to take oral medication or requiring IV alimentation
• No uncontrolled inflammatory GI disease (e.g., Crohn's disease or ulcerative colitis)
• No active peptic ulcer disease

Ophthalmic:

• No ocular inflammation or infection
• No significant ophthalmologic abnormalities, including:

• History of dry eye syndrome, Sjögren's syndrome, or keratoconjunctivitis sicca
• Severe exposure keratopathy
• Disorders that might increase the risk for epithelium-related complications (e.g., bullous keratopathy, aniridia, severe chemical burns, or neutrophilic keratitis)
• Congenital abnormality (e.g., Fuch's dystrophy)
• Abnormal slit-lamp examination using a vital dye (e.g., fluorescein or Bengal-Rose)
• Abnormal corneal sensitivity test (e.g., Schirmer test or similar tear production test)

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No prior allergic reaction to compounds of similar chemical or biological composition to erlotinib
• No other serious illness, medical condition, or significant neurologic or psychiatric disorder that would preclude study therapy
• No active uncontrolled infection
• No grade 3 or greater drug-related neurotoxicity
• No other malignancy within the past 5 years except adequately treated nonmelanoma skin cancer or curatively treated carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas)

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 4 weeks since prior radiotherapy (except low-dose palliative radiotherapy) and recovered

Surgery:

• At least 3 weeks since prior major surgery (wound healing must have occurred)
• No prior surgical procedures affecting gastrointestinal (GI) absorption
• No concurrent ophthalmic surgery

Other:

• No prior therapy targeting epidermal growth factor receptor
• No other concurrent anticancer therapy
• No other concurrent investigational agents
• Concurrent oral anticoagulants (e.g., warfarin) allowed provided INR is monitored