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

NCT ID: NCT00041171

Last Updated: 2016-07-12

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL

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.

Conditions

Adult Solid Tumor; Breast Cancer; Head and Neck Cancer; Kidney and Urinary Cancer; Male Reproductive Cancer; Thorax and Respiratory Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

docetaxel

Intervention Type: DRUG

placebo

Intervention Type: OTHER

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.

Group Type: EXPERIMENTAL

Hypericum perforatum

Intervention Type: DRUG

docetaxel

Intervention Type: DRUG

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.

Group Type: EXPERIMENTAL

Hypericum perforatum

Intervention Type: DRUG

docetaxel

Intervention Type: DRUG

Interventions

Hypericum perforatum

Intervention Type: DRUG

docetaxel

Intervention Type: DRUG

placebo

Intervention Type: OTHER

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Alliance for Clinical Trials in Oncology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lionel D. Lewis, MD

Role: STUDY_CHAIR

Norris Cotton Cancer Center

Other Identifiers

CDR0000069449

Identifier Type: REGISTRY

Identifier Source: secondary_id

CALGB-60002

Identifier Type: -

Identifier Source: org_study_id