Clinical trial NCT00041171: Docetaxel and St. John's Wort in Treating Patients With Solid Tumors That Cannot Be Removed By Surgery
Official title: Phase III Randomized Study of Hypericum Perforatum (St. John's Wort) Combined With Docetaxel in Patients With Unresectable Solid Tumors
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Adult Solid Tumor
Breast Cancer
Head and Neck Cancer
Kidney and Urinary Cancer
Male Reproductive Cancer
Thorax and Respiratory Cancer
Keywords: stage IV breast cancer
stage IIIA breast cancer
recurrent breast cancer
stage IIIB breast cancer
recurrent non-small cell lung cancer
extensive stage small cell lung cancer
recurrent small cell lung cancer
stage III bladder cancer
recurrent bladder cancer
stage IV bladder cancer
stage III prostate cancer
stage IV prostate cancer
recurrent prostate cancer
stage IIIA non-small cell lung cancer
stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer
unspecified adult solid tumor, protocol specific
untreated metastatic squamous neck cancer with occult primary
recurrent metastatic squamous neck cancer with occult primary
metastatic squamous neck cancer with occult primary squamous cell carcinoma
stage III squamous cell carcinoma of the lip and oral cavity
stage III basal cell carcinoma of the lip
stage III verrucous carcinoma of the oral cavity
stage III mucoepidermoid carcinoma of the oral cavity
stage III adenoid cystic carcinoma of the oral cavity
stage IV squamous cell carcinoma of the lip and oral cavity
stage IV basal cell carcinoma of the lip
stage IV verrucous carcinoma of the oral cavity
stage IV mucoepidermoid carcinoma of the oral cavity
stage IV adenoid cystic carcinoma of the oral cavity
recurrent squamous cell carcinoma of the lip and oral cavity
recurrent basal cell carcinoma of the lip
recurrent verrucous carcinoma of the oral cavity
recurrent mucoepidermoid carcinoma of the oral cavity
recurrent adenoid cystic carcinoma of the oral cavity
stage III squamous cell carcinoma of the oropharynx
stage III lymphoepithelioma of the oropharynx
stage IV squamous cell carcinoma of the oropharynx
stage IV lymphoepithelioma of the oropharynx
recurrent squamous cell carcinoma of the oropharynx
recurrent lymphoepithelioma of the oropharynx
stage III squamous cell carcinoma of the nasopharynx
stage III lymphoepithelioma of the nasopharynx
stage IV squamous cell carcinoma of the nasopharynx
stage IV lymphoepithelioma of the nasopharynx
recurrent squamous cell carcinoma of the nasopharynx
recurrent lymphoepithelioma of the nasopharynx
stage III squamous cell carcinoma of the hypopharynx
stage IV squamous cell carcinoma of the hypopharynx
recurrent squamous cell carcinoma of the hypopharynx
stage III squamous cell carcinoma of the larynx
stage III verrucous carcinoma of the larynx
stage IV squamous cell carcinoma of the larynx
stage IV verrucous carcinoma of the larynx
recurrent squamous cell carcinoma of the larynx
recurrent verrucous carcinoma of the larynx
stage III squamous cell carcinoma of the paranasal sinus and nasal cavity
stage III inverting papilloma of the paranasal sinus and nasal cavity
stage III midline lethal granuloma of the paranasal sinus and nasal cavity
stage III esthesioneuroblastoma of the paranasal sinus and nasal cavity
stage IV squamous cell carcinoma of the paranasal sinus and nasal cavity
stage IV inverting papilloma of the paranasal sinus and nasal cavity
stage IV midline lethal granuloma of the paranasal sinus and nasal cavity
stage IV esthesioneuroblastoma of the paranasal sinus and nasal cavity
recurrent squamous cell carcinoma of the paranasal sinus and nasal cavity
recurrent inverting papilloma of the paranasal sinus and nasal cavity
recurrent midline lethal granuloma of the paranasal sinus and nasal cavity
recurrent esthesioneuroblastoma of the paranasal sinus and nasal cavity
recurrent salivary gland cancer
stage III salivary gland cancer
stage IV salivary gland cancer
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Norris Cotton Cancer Center
name: Lionel D. Lewis, MD
role: STUDY_CHAIR
References: