Fallopian Tube Cancer, Primary Peritoneal Cavity Cancer, Recurrent Ovarian Epithelial Cancer, Stage III Ovarian Epithelial Cancer, Stage IV Ovarian Epithelial Cancer
Conditions
Brief summary
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. 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.
Detailed description
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.
Interventions
DRUGtamoxifen citrate
Given orally
DRUGthalidomide
Given orally
OTHERlaboratory biomarker analysis
Correlative studies
Sponsors
Gynecologic Oncology Group
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Median Progression-free Survival | from enrollment onto the study until first disease progression or death due to any cause |
Countries
United States
Participant flow
Recruitment details
Enrollment began Feb 3, 2003 and completed Jan 30, 2011. All patients were enrolled from GOG member institutions in the United States.
Pre-assignment details
Eligible patients had histologically confirmed ovarian, fallopian tube or primary peritoneal cancer. They had rising CA-125 that exceeded twice the upper-limit of normal, but no radiographic or physical evidence of disease following first-line chemotherapy.
Participants by arm
| Arm | Count |
|---|---|
| Grp - 1 Thalidomide 200mg orally daily with weekly escalation of 100mg to a maximum dose of 400mg until progression or additional therapy prohibited further therapy. | 68 |
| Grp - 2 Tamoxifen 20mg orally for up to 12 28-day cycles until progression or adverse effect prohibited additional therapy. | 70 |
| Total | 138 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 21 | 1 |
| Overall Study | Concommitant Illness/Other | 1 | 2 |
| Overall Study | Did not start therapy | 1 | 1 |
| Overall Study | Ineligible | 1 | 0 |
| Overall Study | Withdrawal by Subject | 6 | 6 |
Baseline characteristics
| Characteristic | Grp - 1 | Grp - 2 | Total |
|---|---|---|---|
| Age, Continuous | 64.3 years STANDARD_DEVIATION 10.8 | 61.6 years STANDARD_DEVIATION 10.5 | 62.9 years STANDARD_DEVIATION 10.7 |
| Age, Customized 50-59 years | 17 participants | 14 participants | 31 participants |
| Age, Customized < 50 years | 7 participants | 12 participants | 19 participants |
| Age, Customized 60-69 years | 22 participants | 28 participants | 50 participants |
| Age, Customized 70-79 years | 17 participants | 15 participants | 32 participants |
| Age, Customized 80-89 years | 5 participants | 1 participants | 6 participants |
| Gynecologic Oncology Group (GOG) Performance Status 0 - asymptomatic | 63 participants | 67 participants | 130 participants |
| Gynecologic Oncology Group (GOG) Performance Status 1 - symptomatic | 5 participants | 3 participants | 8 participants |
| Primary Site of Disease Fallopian Tube | 0 participants | 1 participants | 1 participants |
| Primary Site of Disease Ovary | 58 participants | 59 participants | 117 participants |
| Primary Site of Disease Peritoneum | 10 participants | 10 participants | 20 participants |
| Sex: Female, Male Female | 68 Participants | 70 Participants | 138 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 42 / 67 | 24 / 69 |
| serious Total, serious adverse events | 3 / 67 | 1 / 69 |
Outcome results
Primary
Median Progression-free Survival
Time frame: from enrollment onto the study until first disease progression or death due to any cause
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Grp - 1 | Median Progression-free Survival | 3.2 months |
| Grp - 2 | Median Progression-free Survival | 4.5 months |