Combination Chemotherapy in Treating Patients With Metastatic or Unresectable Solid Tumors
Status and phase
Conditions
Treatments
Study type
Funder types
Identifiers
Details and patient eligibility
About
This phase I trial is studying the side effects and best dose of combination chemotherapy in treating patients with metastatic or unresectable solid tumors. Drugs used in chemotherapy, such as docetaxel and 17-N-allylamino-17-demethoxygeldanamycin, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.
Full description
OBJECTIVES:
I. Determine the maximum tolerated dose of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) administered with docetaxel in patients with progressive metastatic prostate cancer or other progressive metastatic or unresectable solid tumors.
II. Determine the pharmacokinetics of this regimen in these patients.
OUTLINE: This is a dose-escalation study of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG). Patients are assigned to 1 of 2 treatment groups.
Group 1: Patients receive docetaxel IV over 1 hour and 17-AAG IV over 1-2 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Group 2: Patients receive docetaxel IV over 30 minutes and 17-AAG as in group 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients per group receive escalating doses of 17-AAG until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Up to 20 additional patients (10 per group) are treated at the MTD.
Patients are followed every 2-3 months.
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
Inclusion Criteria:
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Histologically confirmed metastatic or unresectable malignancy for which standard curative or palliative therapy does not exist or is no longer effective
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Progressive disease manifested by the following parameters
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For prostate cancer:
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Must have castrate, metastatic disease defined by disease progression after surgical castration or treatment with a gonadotropin-releasing hormone (GnRH) analog (testosterone level less than 50 ng/mL)
- Patients who have not undergone surgical orchiectomy should continue on medical therapies to maintain castrate levels of testosterone
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Progressive metastatic disease on imaging studies (bone scan, CT scan, or MRI) OR metastatic disease and a rising prostate-specific antigen (PSA)
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Biochemical progression indicated by at least 3 rising PSA values (obtained at least 1 week apart) from a baseline OR 2 rising PSA values (more than 1 month apart), where the percentage increase over the range of values is at least 25%
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Patients who have received an antiandrogen as part of first-line hormonal therapy must have shown progression of disease off of the antiandrogen prior to study enrollment
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For other solid tumors:
- Development of new lesions or an increase in pre-existing lesions by bone scintigraphy, CT scan, MRI, positron emission tomography, or physical examination
- Patients whose sole criterion for progression is an increase in a biochemical marker (e.g., carcinoembryonic antigen or CA 15-3) or an increase in symptoms are not eligible
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Patients with metastatic disease must not be progressing to the extent as to require palliative treatment within 4 weeks of study entry
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No active brain metastases
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Performance status - Karnofsky 70-100%
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More than 6 months
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WBC at least 3,000/mm^3
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Absolute neutrophil count at least 1,500/mm^3
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Platelet count at least 100,000/mm^3
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Bilirubin ≤ 1.5 times upper limit of normal (ULN)
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AST and ALT < 1.5 times ULN
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PT ≤ 1.1 times ULN
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Creatinine no greater than 1.4 mg/dL or within ULN
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Creatinine clearance greater than 55 mL/min
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No prior history of pulmonary toxicity after receiving anthracyclines (e.g., doxorubicin hydrochloride, daunorubicin hydrochloride, mitoxantrone hydrochloride, bleomycin, or carmustine)
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No dyspnea ≥ grade 2 at rest on room air
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No requirement for supplementary oxygen therapy or oxygen saturations ≤ 88%
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No clinically significant pulmonary comorbidities that require medication (e.g., severe chronic obstructive pulmonary disease that could predispose patient to pulmonary toxicity)
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QTc ≤ 450 msec for male patients (470 for female patients)
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LVEF > 40% by echocardiogram or MUGA
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Echocardiogram or MUGA required for patients with any of the following:
- Myocardial infarction > 1 year ago
- NYHA class I or II CHF
- Atrial fibrillation
- Right or left bundle branch block by EKG
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No history of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row)
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No myocardial infarction within the past year
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No active ischemic heart disease within the past year
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No New York Heart Association (NYHA) class III or IV congestive heart failure (CHF)
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No poorly controlled angina
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No uncontrolled dysrhythmia
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No congenital long QT syndrome
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No left bundle branch block
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No other significant cardiac disease
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No prior history of cardiac toxicity after receiving anthracyclines such as doxorubicin hydrochloride, daunorubicin hydrochloride, mitoxantrone hydrochloride, bleomycin, or carmustine
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Not pregnant or nursing
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Negative pregnancy test
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Fertile patients must use effective contraception
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No history of severe hypersensitivity reaction to paclitaxel, docetaxel, or polysorbate 80
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No ongoing or active infection
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No psychiatric illness or social situation that would preclude study compliance
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No grade 2 or greater symptomatic peripheral neuropathy
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No allergy to eggs or egg products
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No other concurrent uncontrolled illness
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At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
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See Disease Characteristics
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At least 4 weeks since prior radiotherapy and recovered
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No concurrent radiotherapy to sole measurable lesion
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No prior mantle-field radiotherapy
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See Disease Characteristics
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No concurrent surgery for sole measurable lesion
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Recovered from prior therapy
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At least 1 week since prior ketoconazole and recovered
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At least 4 weeks since prior investigational anticancer therapeutic drugs
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No concurrent combination antiretroviral therapy for HIV-positive patients
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No concurrent medications that prolong QTc interval
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No concurrent medication used to control arrhythmias
- Calcium blockers and beta blockers allowed
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No other concurrent investigational agents
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No other concurrent anticancer agents or therapies (investigational or commercial)
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No concurrent CYP3A4 inhibitors, including any of the following:
- Fluconazole
- Itraconazole
- Ketoconazole
- Macrolide antibiotics (azithromycin, clarithromycin, erythromycin, or troleandomycin)
- Nifedipine
- Verapamil
- Diltiazem
- Cyclosporine
- Grapefruit juice
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No concurrent CYP3A4 inducers, including any of the following:
- Carbamazepine
- Phenobarbital
- Phenytoin
- Rifampin
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No concurrent herbal extracts or tinctures with CYP3A4 inhibitory activity, including any of the following:
- Hydrastis canadensis (goldenseal)
- Hypericum perforatum (St. John's wort)
- Uncaria tomentosa (cat's claw)
- Echinacea angustifolia roots
- Trifolium pratense (wild cherry)
- Matricaria chamomilla (chamomile)
- Glycyrrhiza glabra (licorice)
- Dillapiol
- Hypericin
- Naringenin
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Concurrent CYP3A4 substrates allowed
Trial design
Primary purpose
Allocation
Interventional model
Masking
80 participants in 2 patient groups
Trial contacts and locations
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Data sourced from clinicaltrials.gov
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