Medroxyprogesterone Compared With Venlafaxine in Treating Hot Flashes in Women

Alliance for Clinical Trials in Oncology

Status and phase: Completed; Phase 3

Conditions: Hot Flashes

Treatments: Drug: venlafaxine; Drug: medroxyprogesterone

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00030914

CDR0000069217 (Registry Identifier)

NCCTG-N99C7

NCI-P02-0204

Details and patient eligibility

About

RATIONALE: Medroxyprogesterone and venlafaxine may be effective in relieving hot flashes. It is not yet known whether venlafaxine is more effective than medroxyprogesterone in relieving hot flashes.

PURPOSE: Randomized phase III trial to compare the effectiveness of medroxyprogesterone with that of venlafaxine in treating women who are experiencing hot flashes.

Full description

OBJECTIVES:

• Compare the efficacy of medroxyprogesterone administered as 1 injection vs medroxyprogesterone administered as 3 injections (closed to accrual as of 1/22/03) vs venlafaxine for hot flash alleviation in women with symptomatic hot flashes.
• Compare the toxic effects of these regimens in these patients.
• Determine whether there is cross resistance between these 2 drugs in these patients.
• Compare the 1-year efficacy of these regimens in these patients.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to age (18 to 49 vs 50 and over), current tamoxifen use (yes vs no), current raloxifene use (yes vs no), duration of hot flash symptoms (less than 9 months vs 9 months or more), and average frequency of hot flashes per day (2-3 vs 4-9 vs 10 or more). Patients are randomized to 1 of 2 treatment arms. (Arm II closed to accrual as of 1/22/03.)

All patients complete a daily questionnaire regarding number of hot flashes beginning on day 1 and continuing for 7 weeks. Patients are randomized to one of three treatment arms.

Enrollment: 227 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• History of breast cancer, ductal carcinoma in situ, or lobular carcinoma in situ (currently without evidence of malignant disease) OR
• Concerns about taking estrogen for fear of breast cancer
• Bothersome hot flashes, defined as occurrence at least 14 times per week and of sufficient severity as to make patient desire therapeutic intervention
• Presence of hot flashes for at least 1 month
• Hormone receptor status:

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Sex:

• Female

Performance status:

• ECOG 0-1

Life expectancy:

• At least 6 months

Cardiovascular:

• No prior thromboembolic disease
• No uncontrolled hypertension (persistent diastolic blood pressure greater than 95 mm Hg and/or systolic blood pressure greater than 160 mm Hg)

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Chemotherapy:

• More than 4 weeks since prior antineoplastic chemotherapy
• No concurrent antineoplastic chemotherapy unless clinically appropriate

Endocrine therapy:

• More than 4 weeks since prior androgen or estrogen therapy
• More than 3 months since prior progesterone as part of hormone replacement therapy
• At least 1 year since any other progesterone therapy (including megestrol)
• No concurrent androgen, estrogen, or progestational agents unless clinically appropriate
• Concurrent tamoxifen, raloxifene, or aromatase inhibitors are allowed if started more than 4 weeks ago and continuation for more than 5 weeks is planned

Other:

• More than 2 weeks since prior agents for treatment of hot flashes (e.g., clonidine, Bellergal-S, or vitamin E of more than 400 mg per day)
• More than 1 year since prior antidepressants (including Hypericum perforatum [St John's Wort])
• No other concurrent antidepressants or monoamine oxidase inhibitors
• No other concurrent agents for treatment of hot flashes (e.g. clonidine, Bellergal-S, or vitamin E of more than 400 mg per day)

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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227 participants in 3 patient groups

Arm I: venlafaxine

Experimental group

Description:

All patients complete a daily questionnaire regarding number of hot flashes beginning on day 1 and continuing for 7 weeks. Patients receive oral venlafaxine once daily for 6 weeks beginning on day 8. After week 7, patients with satisfactory efficacy may continue venlafaxine for up to 6 months. Patients with unsatisfactory efficacy may cross over to arm III. Patients are followed at months 2, 3, 4, 5, 6, 8, 10, and 12.

Treatment:

Drug: venlafaxine

Arm II: medroxyprogesterone - long term

Experimental group

Description:

All patients complete a daily questionnaire regarding number of hot flashes beginning on day 1 and continuing for 7 weeks. Patients receive medroxyprogesterone intramuscularly (IM) on days 8, 22, and 36 for a total of 3 injections. After week 7, patients with unsatisfactory efficacy may cross over to arm I. Patients are followed at months 2, 3, 4, 5, 6, 8, 10, and 12.

Treatment:

Drug: medroxyprogesterone

Arm III: medroxyprogesterone - short term

Experimental group

Description:

All patients complete a daily questionnaire regarding number of hot flashes beginning on day 1 and continuing for 7 weeks. Patients receive medroxyprogesterone IM once on day 8. After week 7, patients with unsatisfactory efficacy may cross over to arm I. Patients are followed at months 2, 3, 4, 5, 6, 8, 10, and 12.

Treatment:

Drug: medroxyprogesterone