Combination Chemotherapy in Treating Patients With Metastatic or Unresectable Solid Tumors

• Status: Completed
• Trial end date: 2010-03-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Docetaxel

Criteria

Inclusion Criteria:

• Histologically confirmed metastatic or unresectable malignancy for which standard curative or palliative therapy does not exist or is no longer effective

• Progressive disease manifested by the following parameters

• For prostate cancer:

• 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

• Progressive metastatic disease on imaging studies (bone scan, CT scan, or MRI) OR metastatic disease and a rising prostate-specific antigen (PSA)

• 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%

• 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

• 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

• Patients with metastatic disease must not be progressing to the extent as to require palliative treatment within 4 weeks of study entry

• No active brain metastases

• Performance status - Karnofsky 70-100%

• More than 6 months

• WBC at least 3,000/mm^3

• Absolute neutrophil count at least 1,500/mm^3

• Platelet count at least 100,000/mm^3

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)

• AST and ALT < 1.5 times ULN

• PT ≤ 1.1 times ULN

• Creatinine no greater than 1.4 mg/dL or within ULN

• Creatinine clearance greater than 55 mL/min

• No prior history of pulmonary toxicity after receiving anthracyclines (e.g., doxorubicin hydrochloride, daunorubicin hydrochloride, mitoxantrone hydrochloride, bleomycin, or carmustine)

• No dyspnea ≥ grade 2 at rest on room air

• No requirement for supplementary oxygen therapy or oxygen saturations ≤ 88%

• No clinically significant pulmonary comorbidities that require medication (e.g., severe chronic obstructive pulmonary disease that could predispose patient to pulmonary toxicity)

• QTc ≤ 450 msec for male patients (470 for female patients)

• LVEF > 40% by echocardiogram or MUGA

• 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

• No history of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row)

• No myocardial infarction within the past year

• No active ischemic heart disease within the past year

• No New York Heart Association (NYHA) class III or IV congestive heart failure (CHF)

• No poorly controlled angina

• No uncontrolled dysrhythmia

• No congenital long QT syndrome

• No left bundle branch block

• No other significant cardiac disease

• No prior history of cardiac toxicity after receiving anthracyclines such as doxorubicin hydrochloride, daunorubicin hydrochloride, mitoxantrone hydrochloride, bleomycin, or carmustine

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No history of severe hypersensitivity reaction to paclitaxel, docetaxel, or polysorbate 80

• No ongoing or active infection

• No psychiatric illness or social situation that would preclude study compliance

• No grade 2 or greater symptomatic peripheral neuropathy

• No allergy to eggs or egg products

• No other concurrent uncontrolled illness

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

• See Disease Characteristics

• At least 4 weeks since prior radiotherapy and recovered

• No concurrent radiotherapy to sole measurable lesion

• No prior mantle-field radiotherapy

• See Disease Characteristics

• No concurrent surgery for sole measurable lesion

• Recovered from prior therapy

• At least 1 week since prior ketoconazole and recovered

• At least 4 weeks since prior investigational anticancer therapeutic drugs

• No concurrent combination antiretroviral therapy for HIV-positive patients

• No concurrent medications that prolong QTc interval

• No concurrent medication used to control arrhythmias

• Calcium blockers and beta blockers allowed

• No other concurrent investigational agents

• No other concurrent anticancer agents or therapies (investigational or commercial)

• 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

• No concurrent CYP3A4 inducers, including any of the following:

• Carbamazepine

• Phenobarbital

• Phenytoin

• Rifampin

• 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

• Concurrent CYP3A4 substrates allowed