17-N-Allylamino-17-Demethoxygeldanamycin and Paclitaxel in Treating Patients With Metastatic or Unresectable Solid Tumor

NCT ID: NCT00087217

Last Updated: 2013-01-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-05-31

Brief Summary

This phase I trial is studying the side effects and best dose of 17-N-allylamino-17-demethoxygeldanamycin when given together with paclitaxel in treating patients with metastatic or unresectable solid tumor. Drugs used in chemotherapy, such as 17-N-allylamino-17-demethoxygeldanamycin and paclitaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining 17-N-allylamino-17-demethoxygeldanamycin with paclitaxel may kill more tumor cells

Detailed Description

OBJECTIVES:

I. Determine the maximum tolerated dose and recommended phase II dose of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) when administered with paclitaxel in patients with metastatic or unresectable solid malignancy.

II. Determine the dose-limiting and non-dose-limiting toxic effects of this regimen in these patients.

III. Determine the pharmacokinetics of this regimen in these patients. IV. Determine tumor response in patients treated with this regimen.

OUTLINE: This is a multicenter, dose-escalation study of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG). Patients receive 17-AAG IV over 1 hour on days 1*, 4, 8, 11, 15 and 18 and paclitaxel IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

NOTE: *17-AAG is not administered on day 1 of course 1. Cohorts of 3-6 patients 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. Once the MTD is determined, 6-12 patients are treated at the recommended phase II dose.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (tanespimycin, paclitaxel)

Patients receive 17-AAG IV over 1 hour on days 1\*, 4, 8, 11, 15 and 18 and paclitaxel IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

tanespimycin

Intervention Type: DRUG

Given IV

paclitaxel

Intervention Type: DRUG

Given IV

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

pharmacological study

Intervention Type: OTHER

Correlative studies

Interventions

tanespimycin

Given IV

Intervention Type: DRUG

paclitaxel

Given IV

Intervention Type: DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

pharmacological study

Correlative studies

Intervention Type: OTHER

Other Intervention Names

17-AAG; Anzatax; Asotax; TAX; Taxol; pharmacological studies

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed solid malignancy

• Metastatic or unresectable disease
• Not amenable to standard curative or palliative therapy
• No known brain metastases
• Performance status - ECOG 0-2
• More than 12 weeks
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• WBC ≥ 3,000/mm^3
• AST and ALT ≤ 2.5 times upper limit of normal
• Bilirubin normal
• Creatinine normal
• Creatinine clearance ≥ 60 mL/min
• QTc < 450 msec for male patients (470 msec for female patients)
• LVEF > 40% by MUGA
• 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 New York Heart Association class III or IV congestive heart failure
• No poorly controlled angina
• No history of uncontrolled dysrhythmia or requirement for antiarrhythmic drugs
• No history of congenital long QT syndrome
• No active ischemic heart disease within the past year
• No left bundle branch block
• No other significant cardiac disease
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective double barrier contraception for at least 1 week before, during, and for at least 2 weeks after study participation
• No prior allergy to eggs
• No prior allergic reaction to compounds of similar chemical or biologic composition to 17-AAG or paclitaxel
• No peripheral neuropathy > grade 1
• No concurrent uncontrolled illness
• No active or ongoing infection
• No psychiatric illness or social situation that would preclude study compliance
• No concurrent granulocyte colony-stimulating factors
• Prior paclitaxel allowed
• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• No prior 17-N-allylamino-17-demethoxygeldanamycin (17-AAG)
• More than 4 weeks since prior radiotherapy
• No prior radiotherapy that included the heart in the field (e.g., mantle radiotherapy)
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent therapeutic-dose warfarin for anticoagulation
• No concurrent medications that may prolong QTc interval
• No other concurrent investigational agents
• No other concurrent anticancer agents or therapies

• 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

Suresh Ramalingam

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania Medical Center

Locations

University of Pennsylvania Medical Center

Philadelphia, Pennsylvania, United States

Countries

United States

Other Identifiers

PCI-03-152

Identifier Type: -

Identifier Source: secondary_id

U01CA099168

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01CA062502

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000373824

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2012-02610

Identifier Type: -

Identifier Source: org_study_id