Official Title: “A Randomized Study Of Tamoxifen Versus Thalidomide (NSC# 66847) In Patients With Biochemical-Recurrence-Only Epithelial Ovarian Cancer, Cancer Of The Fallopian Tube, And Primary Peritoneal Carcinoma After First Line Chemotherapy”

RATIONALE: Estrogen can stimulate the growth of some types of cancer cells. Hormone therapy using tamoxifen may fight cancer by blocking the uptake of estrogen. Thalidomide may stop the growth of cancer by stopping blood flow to the tumor. It is not yet known whether thalidomide is more effective than tamoxifen in treating ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of tamoxifen with that of thalidomide in treating women who have recurrent ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer.

Study Type: Interventional

Study Design: Treatment, Randomized, Active Control

OBJECTIVES: - Compare the recurrence-free survival of patients with only a biochemical recurrence of ovarian epithelial, fallopian tube, or primary peritoneal cancer after first-line chemotherapy treated with tamoxifen vs thalidomide. - Compare the toxic effects and complications associated with these drugs in these patients. - Determine whether changes in biomarker levels including, serum vascular endothelial growth factor (VEGF) and/or basic fibroblast growth factor (bFGF) in these patients are independent of the randomized drug treatment. - Determine whether biomarker levels including, serum and plasma VEGF and/or bFGF are associated with the duration of recurrence-free survival in patients treated with these drugs.

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.

PROJECTED ACCRUAL: A total of 260 patients will be accrued for this study within 6.5 years.

Intervention(s) in this Clinical Trial

• Drug: tamoxifen citrate
  • Given orally
• Drug: thalidomide
  • Given orally

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Arm I
  • Patients receive oral thalidomide once daily on days 1-28. Courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
• Active Comparator: Arm II
  • Patients receive oral tamoxifen twice daily on days 1-28. Courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

Primary Measures

• Recurrence-free survival
  • Safety Issue?: No
• Toxic effects and complications
  • Safety Issue?: Yes
• Correlation of biomarker levels with drug treatment
  • Safety Issue?: No
• Correlation of biomarker levels with duration of recurrence-free survival
  • Safety Issue?: No

DISEASE CHARACTERISTICS:

• 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

PATIENT CHARACTERISTICS:

Age:

• Not specified

Performance status:

• GOG 0-1

Life expectancy:

• Not specified

Hematopoietic:

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

Hepatic:

• 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

Renal:

• Creatinine no greater than 1.5 times ULN OR
• Creatinine clearance at least 60 mL/min

Cardiovascular:

• No history of deep venous thrombosis
• No prior cerebrovascular accident

Pulmonary:

• No history of pulmonary embolism

Other:

• 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

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior immunotherapy (e.g., interleukins)
• No prior biological response modifiers (e.g., monoclonal antibodies)
• No prior antiangiogenic agents (e.g., carbonic anhydrase inhibitors)

Chemotherapy:

• See Disease Characteristics
• At least 3 weeks since prior anticancer chemotherapy and recovered

Endocrine therapy:

• 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)

Radiotherapy:

• At least 3 weeks since prior anticancer radiotherapy and recovered

Surgery:

• At least 3 weeks since prior anticancer surgery and recovered
• Prior second-look surgery without cytoreduction allowed

Other:

• 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)

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Gynecologic Oncology Group

Overall Clinical Trial Officials and Contacts

Jean A. Hurteau, MD Study Chair Evanston Northwestern Healthcare - Evanston Hospital  

Information obtained from ClinicalTrials.gov on September 04, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00041080

Study ID Number: CDR0000069441

ClinicalTrials.gov Identifier: NCT00041080

Health Authority: United States: Food and Drug Administration

Clinical trial summary from the National Cancer Institute's PDQ® database