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”

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.

Study Type: Interventional

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

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.

Intervention(s) in this Clinical Trial

• Drug: St. John's wort
• Drug: sertraline hydrochloride

Primary Measures

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

Secondary Measures

• 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

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Wake Forest University

Overall Clinical Trial Officials and Contacts

Antonius A. Miller, MD Study Chair Wake Forest University  

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00066859

Study ID Number: CDR0000320508

ClinicalTrials.gov Identifier: NCT00066859

Health Authority: United States: Federal Government

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