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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00087217
First received: July 8, 2004
Last updated: January 24, 2013
Last verified: January 2013
  Purpose

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


Condition Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Drug: tanespimycin
Drug: paclitaxel
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of 17- Allylamino-17 Demethoxygeldanamycin (17-AAG) in Combination With Paclitaxel in Advanced Solid Malignancies

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Phase 2 recommended doses of tanespimycin [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    Tabulated according to the NCI CTC.


Enrollment: 35
Study Start Date: May 2004
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: tanespimycin
Given IV
Other Name: 17-AAG
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00087217

Locations
United States, Pennsylvania
University of Pennsylvania Medical Center
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Investigators
Principal Investigator: Suresh Ramalingam University of Pennsylvania Medical Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00087217     History of Changes
Other Study ID Numbers: NCI-2012-02610, PCI-03-152, U01CA099168, U01CA062502, CDR0000373824
Study First Received: July 8, 2004
Last Updated: January 24, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Paclitaxel
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 15, 2014