Docetaxel and St. John's Wort in Treating Patients With Solid Tumors That Cannot Be Removed By Surgery

Sponsor

Alliance for Clinical Trials in Oncology (Other)

Overall Status

Withdrawn

CT.gov ID

NCT00041171

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Arms

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Adult Solid Tumor Breast Cancer Head and Neck Cancer Kidney and Urinary Cancer Male Reproductive Cancer Thorax and Respiratory Cancer	Drug: Hypericum perforatum Drug: docetaxel Other: placebo	Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

Phase III Randomized Study of Hypericum Perforatum (St. John's Wort) Combined With Docetaxel in Patients With Unresectable Solid Tumors

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1: placebo + docetaxel Patients receive oral placebo three times daily on days 1-14 and docetaxel IV over 1 hour 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.	Drug: docetaxel Other: placebo
Experimental: Arm 2: Hypericum perforatum + docetaxel Patients receive oral Hypericum perforatum three times daily on days 1-14 and docetaxel as in arm 1. 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.	Drug: Hypericum perforatum Drug: docetaxel
Experimental: Arm 3: Hypericum perforatum + docetaxel Patients receive docetaxel as in arm 1 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.	Drug: Hypericum perforatum Drug: docetaxel

Arm

Intervention/Treatment

Experimental: Arm 1: placebo + docetaxel

Patients receive oral placebo three times daily on days 1-14 and docetaxel IV over 1 hour 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.

Drug: docetaxel

Other: placebo

Experimental: Arm 2: Hypericum perforatum + docetaxel

Patients receive oral Hypericum perforatum three times daily on days 1-14 and docetaxel as in arm 1. 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.

Drug: Hypericum perforatum

Drug: docetaxel

Experimental: Arm 3: Hypericum perforatum + docetaxel

Patients receive docetaxel as in arm 1 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.

Drug: Hypericum perforatum

Drug: docetaxel

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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