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: Randomized phase III trial to compare the effectiveness of sertraline with that of St. John's wort in treating mild to moderate depression in patients who have solid tumors.

Condition	Treatment or Intervention	Phase
Depression unspecified adult solid tumor, protocol specific	Drug: Hypericum perforatum  Drug: sertraline  Procedure: biologically based therapies  Procedure: cancer prevention intervention  Procedure: complementary and alternative therapy  Procedure: herbal medicine / botanical therapy  Procedure: nutritional supplementation  Procedure: psychosocial assessment/care  Procedure: supportive care/therapy	Phase III

Further Study Details: 

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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  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

Georgia
      Regional Radiation Oncology Center at Rome, Rome,  Georgia,  30165,  United States; Recruiting
Illinois
      CCOP - Central Illinois, Decatur,  Illinois,  62526,  United States; Recruiting
North Carolina
      Alamance Cancer Center, Burlington,  North Carolina,  27216,  United States; Recruiting
      CCOP - Southeast Cancer Control Consortium, Goldsboro,  North Carolina,  27534-9479,  United States; Recruiting
      Comprehensive Cancer Center at Wake Forest University, Winston Salem,  North Carolina,  27157-1082,  United States; Recruiting
      High Point Regional Hospital, High Point,  North Carolina,  27261,  United States; Recruiting

Study chairs or principal investigators

Antonius A. Miller, MD,  Study Chair,  Comprehensive Cancer Center of Wake Forest University   
Stephen Rapp, PhD,  Comprehensive Cancer Center of Wake Forest University   
Edward G. Shaw, MD,  Comprehensive Cancer Center of Wake Forest University   
W. Vaughn McCall, MD,  Comprehensive Cancer Center of Wake Forest University   

Study ID Numbers:  CDR0000320508; CCCWFU-98101; CCCWFU-BGOI-152; NCT00066859
Record last reviewed:  July 2004
Last Updated:  April 4, 2005
Record first received:  August 6, 2003
ClinicalTrials.gov Identifier:  NCT00066859
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08