Docetaxel and St. John's Wort in Treating Patients With Solid Tumors That Cannot Be Removed By Surgery
Status and phase
Conditions
Treatments
Study type
Funder types
Identifiers
Details and patient eligibility
About
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. St. John's wort may interfere with the effectiveness of chemotherapy. It is not yet known if chemotherapy is more effective with or without St. John's Wort in treating solid tumors.
PURPOSE: Randomized phase III trial to compare the effectiveness of docetaxel with or without St. John's wort in treating patients who have solid tumors that cannot be removed by surgery.
Full description
OBJECTIVES:
- Determine the effect of Hypericum perforatum (St. John's Wort) on the pharmacokinetic clearance of docetaxel in patients with unresectable solid tumors.
- Determine the effect of Hypericum perforatum on the production and plasma concentrations of M4-C13-hydroxydocetaxel in these patients.
- Determine the effects of this drug on the pharmacodynamics of docetaxel in these patients.
- Determine the relationship between the effects of this drug on docetaxel metabolic clearance and CYP3A4/CYP3A5 genotype in these patients.
- Determine the relationship between the effect of this drug on docetaxel metabolic clearance and p-glycoprotein genotype in these patients.
- Determine the relationship between the effect of this drug on docetaxel clearance and pregnane receptor genotype in these patients.
- Assess compliance with this drug in these patients.
- Assess the steady state concentrations of hyperforin, one of the putative psychoactive components of Hypericum perforatum, in these patients.
OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients who have not been receiving chronic Hypericum perforatum (St. John's Wort) are assigned to group A, while a cohort of 8 patients who have been receiving chronic Hypericum perforatum are assigned to group B.
- Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive oral placebo three times daily on days 1-14 and docetaxel IV over 1 hour on day 15.
- Arm II: Patients receive oral Hypericum perforatum three times daily on days 1-14 and docetaxel as in arm I.
- Group B (non-randomized group): Patients receive docetaxel as in arm I and continue to receive their chronic regimen of Hypericum perforatum except on day 15.
Treatment in both groups repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
Patients are followed for new primaries and survival only.
PROJECTED ACCRUAL: Approximately 92 patients will be accrued for this study.
Sex
Ages
Volunteers
Inclusion and exclusion criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed unresectable solid tumor, including, but not limited to, the following:
- Lung cancer
- Breast cancer
- Head and neck cancer
- Bladder cancer
- Prostate cancer
- Must be suitable for treatment with single-agent docetaxel
- Hormone receptor status:
- Not specified
PATIENT CHARACTERISTICS:
Age:
- 18 and over
Sex:
- Male or female
Menopausal status:
- Not specified
Performance status:
- CTC 0-2
Life expectancy:
- Not specified
Hematopoietic:
- Granulocyte count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
Hepatic:
- Bilirubin less than upper limit of normal (ULN)
- Alkaline phosphatase less than 2.5 times ULN
Renal:
- Creatinine no greater than 1.5 times ULN
- BUN no greater than 1.5 times ULN
Other:
- Not pregnant or nursing
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- No prior bone marrow transplantation
- No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF)
Chemotherapy:
- See Disease Characteristics
- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
- No prior docetaxel
- No more than 2 prior chemotherapy regimens
- No other concurrent chemotherapy
Endocrine therapy:
- No concurrent hormonal agents except steroids for adrenal failure or hormones for non-disease-related conditions (e.g., insulin for diabetes)
Radiotherapy:
- At least 3 weeks since prior radiotherapy
- No concurrent palliative radiotherapy
Surgery:
- At least 4 weeks since prior major surgery
Other:
- At least 6 months since prior Hypericum perforatum (St. John's Wort)
- At least 1 week since prior CYP3A enzyme inducers including:
- Phenobarbital
- Phenytoin
- Carbamazepine
- Lamotrigine
- Rifampin
- Rifabutin
- Isoniazid
- Sulfinpyrazone
- Pioglitazone
- Anti-HIV drugs such as efavirenz or nevirapine
- At least 1 week since prior CYP3A enzyme inhibitors including:
- Erythromycin
- Clarithromycin
- Azithromycin
- Roxithromycin
- Ketoconazole
- Fluconazole
- Itraconazole
- Metronidazole
- Chloramphenicol
- Ritonavir
- Saquinavir
- Indinavir
- Nelfinavir mesylate
- Delavirdine
- Amiodarone
- Cyclosporine
- Tacrolimus
- Sirolimus
- Nefazodone
- Fluvoxamine
- No concurrent CYP3A enzyme inducers
- No concurrent CYP3A enzyme inhibitors
- No ethanol (especially red wine), grape fruit juice, or seville orange juice (CYP3A enzyme inhibitor) within 3 days before or after receiving docetaxel
Trial design
Primary purpose
Allocation
Interventional model
Masking
0 participants in 3 patient groups
Trial contacts and locations
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Data sourced from clinicaltrials.gov
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