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

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00041080
• Collaborator: Gynecologic Oncology Group (Other)
• Enrollment: 139
• Location: 1
• Arms: 2
• Duration (Months): 95
• Patients Per Site Per Month: 1.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Fallopian Tube Cancer; Primary Peritoneal Cavity Cancer; Recurrent Ovarian Epithelial Cancer; Stage III Ovarian Epithelial Cancer; Stage IV Ovarian Epithelial Cancer	Drug: tamoxifen citrate; Drug: thalidomide; Other: laboratory biomarker analysis	Phase 3

Detailed Description

PRIMARY OBJECTIVES:

1. 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.

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

SECONDARY OBJECTIVES:

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

2. 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 Design

• Study Type: Interventional
• Actual Enrollment: 139 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Study Start Date: Feb 1, 2003
• Actual Primary Completion Date: Jan 1, 2011
• Actual Study Completion Date: Jan 1, 2011

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Median Progression-free Survival [from enrollment onto the study until first disease progression or death due to any cause]

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: Female
• Accepts 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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Gynecologic Oncology Group	Philadelphia	Pennsylvania	United States	19103

Sponsors and Collaborators

• National Cancer Institute (NCI)
• Gynecologic Oncology Group

Investigators

• Principal Investigator: Jean Hurteau, Gynecologic Oncology Group

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00041080
• Other Study ID Numbers: NCI-2012-02475; NCI-2012-02475; CDR0000069441; GOG-0198; GOG-0198; U10CA027469
• First Posted: Jan 27, 2003
• Last Update Posted: Jul 30, 2019
• Last Verified: Jul 1, 2019

• Additional relevant MeSH terms: Fallopian Tube Neoplasms; Carcinoma, Ovarian Epithelial; Tamoxifen; Thalidomide

Study Results

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 Detail	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.

Arm/Group Title	Grp - 1	Grp - 2
Arm/Group Description	Thalidomide 200mg orally daily with weekly escalation of 100mg to a maximum dose of 400mg until progression or additional therapy prohibited further therapy.	Tamoxifen 20mg orally twice daily for up to 12 28-day cycles until progression or adverse effect prohibited additional therapy.
Period Title: Overall Study
STARTED	69	70
COMPLETED	39	60
NOT COMPLETED	30	10

Baseline Characteristics

Arm/Group Title	Grp - 1	Grp - 2	Total
Arm/Group Description	Thalidomide 200mg orally daily with weekly escalation of 100mg to a maximum dose of 400mg until progression or additional therapy prohibited further therapy.	Tamoxifen 20mg orally for up to 12 28-day cycles until progression or adverse effect prohibited additional therapy.	Total of all reporting groups
Overall Participants	68	70	138
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.3 (10.8)	61.6 (10.5)	62.9 (10.7)
Age, Customized (participants) [Number]
< 50 years	7 10.3%	12 17.1%	19 13.8%
50-59 years	17 25%	14 20%	31 22.5%
60-69 years	22 32.4%	28 40%	50 36.2%
70-79 years	17 25%	15 21.4%	32 23.2%
80-89 years	5 7.4%	1 1.4%	6 4.3%
Sex: Female, Male (Count of Participants)
Female	68 100%	70 100%	138 100%
Male	0 0%	0 0%	0 0%
Gynecologic Oncology Group (GOG) Performance Status (participants) [Number]
0 - asymptomatic	63 92.6%	67 95.7%	130 94.2%
1 - symptomatic	5 7.4%	3 4.3%	8 5.8%
Primary Site of Disease (participants) [Number]
Ovary	58 85.3%	59 84.3%	117 84.8%
Peritoneum	10 14.7%	10 14.3%	20 14.5%
Fallopian Tube	0 0%	1 1.4%	1 0.7%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Grp - 1	Grp - 2
Arm/Group Description	Thalidomide 200mg orally daily with weekly escalation of 100mg to a maximum dose of 400mg until progression or additional therapy prohibited further therapy.	Tamoxifen 20mg orally for up to 12 28-day cycles until progression or adverse effect prohibited additional therapy.
Measure Participants	68	70
Median (95% Confidence Interval) [months]	3.2	4.5

Adverse Events

Time Frame	Within 30 days after stopping study treatment or any SAE that the study investigator felt was study treatment related.
Adverse Event Reporting Description	Other Adverse Events(AEs) are at least possibly related to study treatment. Due to the methods in which adverse events were collected and/or stored for this study, it is not possible to report only the Other (not including Serious) AEs in the appropriate table. Therefore, the Other AEs table includes a combined set of serious and non-serious AEs.
Arm/Group Title	Grp - 1		Grp - 2
Arm/Group Description	Thalidomide 200mg orally daily with weekly escalation of 100mg to a maximum dose of 400mg until progression or additional therapy prohibited further therapy.		Tamoxifen 20mg orally for up to 12 28-day cycles until progression or adverse effect prohibited additional therapy.
All Cause Mortality
	Grp - 1		Grp - 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Grp - 1		Grp - 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/67 (4.5%)		1/69 (1.4%)
Blood and lymphatic system disorders
Neutropenia/Granulocytopenia	1/67 (1.5%)		0/69 (0%)
Edema	1/67 (1.5%)		0/69 (0%)
Cardiac disorders
Sinus tachycardia	1/67 (1.5%)		0/69 (0%)
Thrombosis/embolism	1/67 (1.5%)		1/69 (1.4%)
Gastrointestinal disorders
Constipation	3/67 (4.5%)		0/69 (0%)
Diarrhea	1/67 (1.5%)		0/69 (0%)
Nausea	0/67 (0%)		1/69 (1.4%)
Partial small bowel obstruction	1/67 (1.5%)		0/69 (0%)
General disorders
Fatigue	1/67 (1.5%)		0/69 (0%)
Hepatobiliary disorders
SGPT	1/67 (1.5%)		0/69 (0%)
Infections and infestations
Febrile Neutropenia	1/67 (1.5%)		0/69 (0%)
Nervous system disorders
Neuropathy - motor	1/67 (1.5%)		0/69 (0%)
Tremor	1/67 (1.5%)		0/69 (0%)
Dizziness/lightheadedness	1/67 (1.5%)		0/69 (0%)
Other (Not Including Serious) Adverse Events
	Grp - 1		Grp - 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	42/67 (62.7%)		24/69 (34.8%)
Blood and lymphatic system disorders
Leukopenia	25/67 (37.3%)		8/69 (11.6%)
Neutropenia	21/67 (31.3%)		5/69 (7.2%)
Thrombocytopenia	6/67 (9%)		4/69 (5.8%)
Anemia	15/67 (22.4%)		10/69 (14.5%)
Cardiac disorders
DVT/thrombosis	4/67 (6%)		1/69 (1.4%)
Other cardiovascular	11/67 (16.4%)		6/69 (8.7%)
Endocrine disorders
Endocrine	1/67 (1.5%)		24/69 (34.8%)
Eye disorders
Ocular/visual	11/67 (16.4%)		2/69 (2.9%)
Gastrointestinal disorders
Gastrointestinal	42/67 (62.7%)		22/69 (31.9%)
General disorders
Constitutional	42/67 (62.7%)		18/69 (26.1%)
Pain	26/67 (38.8%)		19/69 (27.5%)
Metabolism and nutrition disorders
Metabolic	8/67 (11.9%)		8/69 (11.6%)
Musculoskeletal and connective tissue disorders
Musculoskeletal	2/67 (3%)		4/69 (5.8%)
Nervous system disorders
Somnolence	17/67 (25.4%)		0/69 (0%)
Other neurologic	32/67 (47.8%)		2/69 (2.9%)
Peripheral neurologic	32/67 (47.8%)		9/69 (13%)
Reproductive system and breast disorders
Genitourinary/renal	3/67 (4.5%)		5/69 (7.2%)
Respiratory, thoracic and mediastinal disorders
Pulmonary	11/67 (16.4%)		1/69 (1.4%)
Skin and subcutaneous tissue disorders
Dermatologic	22/67 (32.8%)		4/69 (5.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.