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

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

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.

Study Overview

• Status: Completed
• Conditions: Fallopian Tube Cancer; Stage IV Ovarian Epithelial Cancer; Primary Peritoneal Cavity Cancer; Recurrent Ovarian Epithelial Cancer; Stage III Ovarian Epithelial Cancer
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: tamoxifen citrate; Drug: thalidomide

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.

• Study Type: Interventional
• Enrollment (Actual): 139
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19103
      • Gynecologic Oncology Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (thalidomide); Patients receive oral thalidomide once daily on days 1-28.	Other: laboratory biomarker analysis; Correlative studies; Drug: thalidomide; Given orally; Other Names: Kevadon; Synovir; THAL; Thalomid
Experimental: Arm II (tamoxifen); Patients receive oral tamoxifen twice daily on days 1-28.	Other: laboratory biomarker analysis; Correlative studies; Drug: tamoxifen citrate; Given orally; Other Names: Nolvadex; TAM; tamoxifen; TMX

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Median Progression-free Survival	from enrollment onto the study until first disease progression or death due to any cause

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Collaborators: Gynecologic Oncology Group
• Investigators: Principal Investigator: Jean Hurteau, Gynecologic Oncology Group

Study record dates

Study Major Dates

• Study Start: February 1, 2003
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): January 1, 2011

Study Registration Dates

• First Submitted: July 8, 2002
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Actual): July 30, 2019
• Last Update Submitted That Met QC Criteria: July 22, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Fallopian Tube Diseases; Ovarian Neoplasms; Fallopian Tube Neoplasms; Carcinoma, Ovarian Epithelial; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Hormone Antagonists; Bone Density Conservation Agents; Estrogen Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Thalidomide; Tamoxifen
• Other Study ID Numbers: NCI-2012-02475 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA027469 (U.S. NIH Grant/Contract); CDR0000069441; GOG-0198 (Other Identifier: CTEP)