A Phase II Evaluation Of Capecitabine (NSC #712807) In The Treatment Of Persistent Or Recurrent Non-Squamous Cell Carcinoma Of The Cervix
A Phase II Evaluation Of Capecitabine (NSC #712807) In The Treatment Of Persistent Or Recurrent Non-Squamous Cell Carcinoma Of The Cervix
Phase II trial to study the effectiveness of capecitabine in treating patients who have persistent or recurrent cervical cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.
PRIMARY OBJECTIVES:
I. Determine the antitumor activity of capecitabine in patients with persistent or recurrent non-squamous cell carcinoma of the cervix who have failed higher priority treatment protocols.
II. Determine the nature and degree of toxicity of this drug in these patients. III. Determine whether the mRNA tumor expression levels of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and thymidine phosphorylase (TP) at baseline are potential predictors of clinical outcomes (response and survival) in patients treated with this drug.
IV. Determine whether the serum level of TP is a potential prognostic indicator of clinical outcomes (response and survival) in patients treated with this drug.
V. Determine whether the TS promoter polymorphism in peripheral blood is a potential prognostic indicator of clinical outcomes (response and survival) in patients treated with this drug.
VI. Determine the associations among the various measures of TS, DPD, and TP and clinical outcomes (response and survival) in patients treated with this drug.
OUTLINE: This is a multicenter study.
Patients receive oral capecitabine twice daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
Inclusion Criteria:
Histologically confirmed primary non-squamous cell carcinoma (non-SCC) of the cervix
Persistent or recurrent disease
Eligible subtypes include:
Documented disease progression
At least 1 unidimensionally measurable target lesion outside prior irradiation field
Received 1 prior systemic chemotherapy regimen for advanced, metastatic, or recurrent non-SCC of the cervix
Tissue blocks from initial diagnosis, metastasis, or recurrence available for submission to the GOG tissue bank
Ineligible for higher priority Gynecologic Oncology Group (GOG) protocol (if one exists), defined as any Temporarily closed GOG phase III protocol for the same patient population
Performance status - GOG 0-2
Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3
Bilirubin no greater than 1.5 times upper limit of normal (ULN)
SGOT no greater than 2.5 times ULN
Alkaline phosphatase no greater than 2.5 times ULN
Creatinine clearance at least 50 mL/min
Not pregnant
Negative pregnancy test
Fertile patients must use effective contraception
No Temporarily closed infection requiring antibiotics
No grade 2 or greater sensory or motor neuropathy
No other invasive malignancy within the past 5 years except nonmelanoma skin cancer
At least 3 weeks since prior biological or immunological anticancer agents
No more than 1 prior non-cytotoxic biologic therapy or cytostatic regimen (e.g., monoclonal antibodies, cytokines, or small-molecule inhibitors of signal transduction) for recurrent or persistent non-SCC of the cervix
See Disease Characteristics
See Biologic therapy
At least 3 weeks since prior chemotherapy and recovered
No prior capecitabine
No more than 1 prior cytotoxic chemotherapy regimen (either with single or combination cytotoxic drug therapy)
At least 1 week since prior hormonal anticancer therapy
Concurrent hormone replacement therapy allowed
See Disease Characteristics
At least 3 weeks since prior radiotherapy and recovered
Recovered from prior recent surgery
At least 3 weeks since other prior anticancer therapy
No prior cancer treatment that would preclude this study therapy