Combination Chemotherapy in Treating Patients With Metastatic or Unresectable Solid Tumors

NCT ID: NCT00058253

Last Updated: 2014-06-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-02-28
• Study Completion Date: 2010-03-31

Brief 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.

Detailed 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.

Conditions

Recurrent Prostate Cancer; Stage IV Prostate Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group I

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 Type: EXPERIMENTAL

tanespimycin

Intervention Type: DRUG

Given IV

docetaxel

Intervention Type: DRUG

Given IV

Group II

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.

Group Type: EXPERIMENTAL

tanespimycin

Intervention Type: DRUG

Given IV

docetaxel

Intervention Type: DRUG

Given IV

Interventions

tanespimycin

Given IV

Intervention Type: DRUG

docetaxel

Given IV

Intervention Type: DRUG

Other Intervention Names

17-AAG; RP 56976; Taxotere; TXT

Eligibility 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

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

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Solit

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Countries

United States

Other Identifiers

NCI-2012-01436

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-5878

Identifier Type: -

Identifier Source: secondary_id

CDR0000287199

Identifier Type: -

Identifier Source: secondary_id

MSKCC-03006

Identifier Type: -

Identifier Source: secondary_id

03-006

Identifier Type: OTHER

Identifier Source: secondary_id

5878

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA008748

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01CA069856

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2012-01436

Identifier Type: -

Identifier Source: org_study_id