Sertraline Compared With Hypericum Perforatum (St. John's Wort) in Treating Mild to Moderate Depression in Patients With Cancer

Condition(s) targeted: Depression; Unspecified Adult Solid Tumor, Protocol Specific

Intervention: St. John's wort (Drug); sertraline hydrochloride (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Wake Forest University

Official(s) and/or principal investigator(s):
Antonius A. Miller, MD, Study Chair, Affiliation: Wake Forest University
Stephen Rapp, PhD, Affiliation: Wake Forest University
Edward G. Shaw, MD, Affiliation: Wake Forest University
W. Vaughn McCall, MD, Affiliation: Wake Forest University

RATIONALE: Antidepressants such as sertraline and the herb hypericum perforatum (St. John's wort) may be effective in treating mild to moderate depression. It is not yet known which treatment is more effective in improving depression in patients who have cancer.

PURPOSE: This randomized phase III trial is studying how well sertraline works compared to St. John's wort in treating mild to moderate depression in patients with solid tumors.

Official title: A Phase III Double-Blind Randomized Trial Comparing Sertraline (Zoloft) And Hypericum Perforatum (St. John's Wort) In Cancer Patients With Mild To Moderate Depression

Study design: Supportive Care, Randomized, Double-Blind, Active Control

Primary outcome: Compare the change in depression severity as measured by Hamilton Depression rating scale at 4 months

Secondary outcome:

Compare the severity of somnolence, nausea, and insomnia at 4 months

Compare the impact of therapy at 4 months

Correlate the hyperforin concentrations with the change in depression severity at 4 months

Detailed description: OBJECTIVES:

- Compare the change in depression severity in cancer patients with mild to moderate

depression treated with sertraline vs Hypericum perforatum.

- Compare the severity of somnolence, nausea, and insomnia in patients treated with these

regimens.

- Compare the impact of these regimens on fatigue in these patients.

- Correlate hyperforin concentrations with change in depression severity in patients

treated with Hypericum perforatum.

OUTLINE: This is a randomized, double-blind study. Patients are stratified according to level of depression (mild vs moderate), concurrent radiotherapy (yes vs no), and TNM stage (I, II, or III vs IV). Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive oral sertraline daily.

- Arm II: Patients receive oral Hypericum perforatum daily. In both arms, treatment

continues for 4 months in the absence of unacceptable toxicity.

Measurements of depression, somnolence, nausea, insomnia, fatigue, and hyperforin concentration are assessed at baseline, and at 1, 2, and 4 months.

PROJECTED ACCRUAL: A maximum of 250 patients will be accrued for this study.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed solid tumor

- No hematologic malignancy (e. g., leukemia, lymphoma, or multiple myeloma)

- Diagnosis of mild to moderate depression

- No severe depression or suicidal ideation

- No psychotic symptoms, dementia, or marked agitation requiring medication

- No brain metastases or primary brain tumor

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- ECOG 0-1

Life expectancy

- More than 4 months

Hematopoietic

- Hemoglobin greater than 10 g/dL

Hepatic

- Bilirubin no greater than 1. 5 mg/dL

Renal

- Not specified

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No prior or concurrent alcohol abuse or drug dependence

PRIOR CONCURRENT THERAPY:

Biologic therapy

- No concurrent epoetin alfa (e. g., Procrit® or Aranesp®)

Chemotherapy

- At least 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas)

- No concurrent chemotherapy

Endocrine therapy

- No concurrent corticosteroids

Radiotherapy

- Prior or concurrent radiotherapy allowed except brain irradiation for brain metastases

or primary brain tumor

Surgery

- Not specified

Other

- More than 4 weeks since prior antidepressants or Hypericum perforatum

- No concurrent warfarin (central line prophylaxis allowed)

- No concurrent administration of any of the following:

- Theophylline

- Protease inhibitors used to treat AIDS

- Digoxin

- Cyclosporine

- Benzodiazepines (e. g., diazepam or alprazolam)

- Calcium-channel blockers (e. g., diltiazem or nifedipine)

- Coenzyme A reductase inhibitors (cholesterol-lowering agents)

- Macrolide antibiotics (e. g., azithromycin, erythromycin, or clarithromycin)

- Griseofulvin

- Phenobarbital

- Phenytoin

- Rifampin

- Rifabutin

- Ketoconazole

- Fluconazole

- Itraconazole

- Grapefruit juice

- Naturopathic/herbal products that would interfere with Hypericum perforatum

Bay Area Tumor Institute, Oakland, California 94609-3305, United States

Regional Radiation Oncology Center at Rome, Rome, Georgia 30165, United States

CCOP - Central Illinois, Decatur, Illinois 62526, United States

CCOP - Southeast Cancer Control Consortium, Goldsboro, North Carolina 27534-9479, United States

Comprehensive Cancer Center at Wake Forest University, Winston-Salem, North Carolina 27157-1082, United States

High Point Regional Hospital, High Point, North Carolina 27261, United States

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

Starting date: August 2003
Last updated: May 23, 2008