Tamoxifen Compared With Thalidomide in Treating Women With Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

PRIMARY OBJECTIVES:

I. To compare the recurrence-free survival of women receiving tamoxifen or thalidomide for epithelial ovarian cancer, cancer of the fallopian tube, or primary peritoneal carcinoma who are in complete clinical remission following front-line treatment but have a high risk of recurrence due to rising serum CA-125.

II. To compare the toxicities and complications of these treatments.

SECONDARY OBJECTIVES:

I. To determine whether changes in serum biomarker levels including VEGF and/or bFGF are independent of the randomization treatment.

II. To determine whether serum and plasma biomarker levels including VEGF and/or bFGF are associated with the duration of recurrence-free survival.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to the interval between completion of front-line chemotherapy and appearance of biochemical progression (6 months or less vs more than 6 months). Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive oral thalidomide once daily on days 1-28.

ARM II: Patients receive oral tamoxifen twice daily on days 1-28.

In both arms, courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients may receive additional therapy beyond 1 year at the investigator's discretion.

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

Inclusion criteria

• Histologically confirmed stage III or IV ovarian epithelial, fallopian tube, or primary peritoneal cancer that was treated with only 1 prior first-line chemotherapy regimen (platinum/taxane-based)
• Clinically and radiologically without evidence of measurable and nonmeasurable disease

• Symptomatic ascites and pleural effusions are considered nonmeasurable disease
• Must have a biochemical recurrence

• CA 125 must have been normal prior to or normalized during first-line therapy and then subsequently rose to exceed twice the upper limit of normal
• Patients entering study with a CA 125 level less than 100 U/mL must be confirmed a second time within a period of not more than 4 weeks
• Patients with a CA 125 level of at least 100 U/mL may be entered without confirmatory measurement
• Ineligible for a higher priority Gynecologic Oncology Group protocol (if one exists)
• No history of brain metastases
• Performance status - GOG 0-1
• 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 no greater than 1.5 times ULN
• Creatinine clearance at least 60 mL/min
• No history of deep venous thrombosis
• No prior cerebrovascular accident
• No history of pulmonary embolism
• No significant infection
• No grade 2 or greater sensory or motor neuropathy
• No other malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use at least 1 highly active method and at least 1 additional effective method of contraception for 4 weeks before, during, and for 4 weeks after study participation
• No prior immunotherapy (e.g., interleukins)
• No prior biological response modifiers (e.g., monoclonal antibodies)
• No prior antiangiogenic agents (e.g., carbonic anhydrase inhibitors)
• At least 3 weeks since prior anticancer chemotherapy and recovered
• No prior or concurrent tamoxifen or other selective estrogen receptor modulators
• At least 4 weeks since prior and no concurrent hormones (e.g., estrogen or progesterone)
• At least 3 weeks since prior anticancer radiotherapy and recovered
• At least 3 weeks since prior anticancer surgery and recovered
• Prior second-look surgery without cytoreduction allowed
• At least 3 weeks since other prior anticancer therapy and recovered
• No prior interval cytoreduction
• No concurrent full-dose therapeutic anticoagulation
• No concurrent antiseizure medications for seizure disorder
• No concurrent bisphosphonates (e.g., zoledronate)