Combination Chemotherapy in Treating Patients With Metastatic or Unresectable Solid Tumors

Unspecified Adult Solid Tumor, Protocol Specific Clinical Trial

Official title:

A Phase I Study of 17-N-Allylamino-17-Demethoxy Geldanamycin (17-AAG, NSC# 330507) in Combination With Docetaxel in Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00058253
• Other study ID #: NCI-2012-01436
• Secondary ID: NCI-2012-01436NC
• Status: Completed
• Phase: Phase 1
• First received: April 7, 2003
• Last updated: June 16, 2014
• Start date: February 2003
• Est. completion date: March 2010

Study information

• Verified date: December 2012
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: March 2010
• Est. primary completion date: January 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Prostatic Neoplasms
• Recurrent Prostate Cancer
• Stage IV Prostate Cancer
• Unspecified Adult Solid Tumor, Protocol Specific

Intervention

Drug:
• tanespimycin
Given IV
• docetaxel
Given IV

Locations

Country	Name	City	State
United States	Memorial Sloan-Kettering Cancer Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose determined by dose-limiting toxicities assessed using the NCI Common Toxicity Criteria (CTC) version 2.0		28 days	Yes