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17-N-Allylamino-17-Demethoxygeldanamycin (17-AAG) and Bortezomib in Treating Patients With Advanced Solid Tumors or Lymphomas
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), August 2009
First Received: November 9, 2004   Last Updated: January 19, 2010   History of Changes
Sponsor: Mayo Clinic
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00096005
  Purpose

RATIONALE: Drugs used in chemotherapy, such as 17-AAG, work in different ways to stop cancer cells from dividing so they stop growing or die. Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for their growth. It may also increase the effectiveness of 17-AAG by making cancer cells more sensitive to the drug. Combining 17-AAG with bortezomib may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of giving 17-AAG together with bortezomib in treating patients with advanced solid tumorsor lymphomas. (Accrual for lymphoma patients closed as of 11/27/09)


Condition Intervention Phase
Lymphoma
Unspecified Adult Solid Tumor, Protocol Specific
Drug: bortezomib
Drug: tanespimycin
Phase I

Study Type: Interventional
Study Design: Treatment
Official Title: A Phase I Trial Of 17-Allylaminogeldanamycin (17-AAG) And PS341 In Advanced Malignancies

Resource links provided by NLM:


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

Estimated Enrollment: 36
Study Start Date: November 2004
Estimated Primary Completion Date: November 2006 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • Determine the dose-limiting toxicity and maximum tolerated dose of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) and bortezomib in patients with advanced solid tumors or lymphomas (Accrual for Lymphoma Patients Closed as of 11/27/09).
  • Determine changes in biomarkers (e.g., HSP70, client proteins, and ubiquitination of proteins) in peripheral blood mononuclear cells and tumor specimens from patients with advanced solid tumors or lymphomas(Accrual for Lymphoma Patients Closed as of 11/27/09) treated with this regimen.
  • Determine responses in patients treated with this regimen.
  • Determine the toxic effects of this regimen in these patients.

OUTLINE: This is a dose-escalation, multicenter study.

Patients receive 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) IV over 1-2 hours and bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of 17-AAG and bortezomib 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, at least 12 additional patients are treated as above* at the MTD.

NOTE: *Bortezomib is not administered on day 1 of course 1 only.

Patients are followed at 3 months.

PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed solid tumor or lymphomas (Accrual for Lymphoma Patients Closed as of 11/27/09)
  • Refractory to standard treatment OR no standard treatment that is potentially curative or capable of prolonging life expectancy exists
  • Tumor amenable to biopsy (patients accrued at the MTD only)
  • No CNS metastases

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-2

Life expectancy

  • At least 12 weeks

Hematopoietic

  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 9.0 g/dL

Hepatic

  • Bilirubin ≤ 2 times upper limit of normal (ULN)
  • AST ≤ 2.5 times ULN
  • Alkaline phosphatase ≤ 2 times ULN (5 times ULN if due to liver involvement)

Renal

  • Creatinine ≤ 2 times ULN

Cardiovascular

  • QTc < 500 msec for men (470 msec for women)
  • LVEF > 40% by echocardiogram
  • Ejection fraction normal by echocardiogram (for patients who have received prior anthracycline therapy)
  • No cardiac symptoms ≥ grade 2
  • No New York Heart Association class III or IV heart failure
  • No myocardial infarction within the past year
  • No active ischemic heart disease within the past year
  • No congenital long QT syndrome
  • No left bundle branch block
  • No history of uncontrolled dysrhythmias or requiring antiarrhythmic drugs
  • No history of cardiac toxicity after receiving anthracyclines (e.g., doxorubicin hydrochloride, daunorubicin hydrochloride, mitoxantrone hydrochloride, bleomycin, or carmustine)
  • No poorly controlled angina
  • No history of serious ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row)
  • No other significant cardiac disease

Pulmonary

  • Pulse oximetry at rest and exercise < 88% (per Medicare guidelines)
  • No pulmonary symptoms ≥ grade 2
  • No significant pulmonary disease requiring oxygen supplementation or causing a severe limitation in activity
  • No symptomatic pulmonary disease requiring medication including any of the following:

    • Dyspnea on or off exertion
    • Paroxysmal nocturnal dyspnea
    • Oxygen requirement and significant pulmonary disease, including chronic obstructive/restrictive pulmonary disease
  • No home oxygen use that meets the Medicare criteria
  • No history of pulmonary toxicity after receiving anthracyclines (e.g., doxorubicin hydrochloride, daunorubicin hydrochloride, mitoxantrone hydrochloride, bleomycin, or carmustine)

Neurologic

  • No seizure disorder
  • No sensory peripheral neuropathy > grade 1
  • No neuropathic pain of any etiology

    • Patients with residual peripheral neuropathy ≤ grade 1 due to oxaliplatin therapy allowed

Other

  • No uncontrolled infection
  • No prior serious allergic reaction to eggs
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Willing to return to Mayo Clinic Rochester, Mayo Clinic Arizona, or Mayo Clinic Florida for follow up

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • More than 4 weeks since prior immunotherapy or biologic therapy
  • No concurrent prophylactic colony-stimulating factors
  • No concurrent immunotherapy, biologic therapy, or gene therapy

Chemotherapy

  • More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
  • No other concurrent chemotherapy

Endocrine therapy

  • Concurrent steroids (at a stable dose for ≥ 4 weeks) for comorbid conditions (e.g., adrenal insufficiency or rheumatoid arthritis) allowed

Radiotherapy

  • More than 4 weeks since prior radiotherapy
  • No prior radiotherapy that potentially included the heart in the field (e.g., mantle) or chest
  • No prior radiotherapy to > 25% of bone marrow
  • No prior radiopharmaceuticals
  • No concurrent radiotherapy

Surgery

  • Not specified

Other

  • Recovered from prior therapy
  • More than 8 weeks since prior UCN-01
  • No concurrent warfarin

    • Low molecular weight heparin allowed
  • No concurrent medications that prolong or may prolong QTc interval
  • No other concurrent investigational therapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00096005

Locations
United States, Florida
Mayo Clinic - Jacksonville Recruiting
Jacksonville, Florida, United States, 32224
Contact: Clinical Trials Office - All Mayo Clinic Locations     507-538-7623        
United States, Minnesota
Mayo Clinic Cancer Center Recruiting
Rochester, Minnesota, United States, 55905
Contact: Clinical Trials Office - All Mayo Clinic Locations     507-538-7623        
Sponsors and Collaborators
Mayo Clinic
Investigators
Study Chair: Charles Erlichman, MD Mayo Clinic
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000391837, MAYO-MC0214, NCI-6121
Study First Received: November 9, 2004
Last Updated: January 19, 2010
ClinicalTrials.gov Identifier: NCT00096005     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
unspecified adult solid tumor, protocol specific
recurrent adult T-cell leukemia/lymphoma
stage III adult T-cell leukemia/lymphoma
stage IV adult T-cell leukemia/lymphoma
adult grade III lymphomatoid granulomatosis
AIDS-related peripheral/systemic lymphoma
anaplastic large cell lymphoma
angioimmunoblastic T-cell lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
stage III adult Burkitt lymphoma
stage III adult diffuse large cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage III adult Hodgkin lymphoma
stage III adult immunoblastic large cell lymphoma
stage III adult lymphoblastic lymphoma
stage III cutaneous T-cell non-Hodgkin lymphoma
stage III mycosis fungoides/Sezary syndrome
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage III mantle cell lymphoma
stage III marginal zone lymphoma
stage III small lymphocytic lymphoma
stage IV adult Burkitt lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse small cleaved cell lymphoma
stage IV adult Hodgkin lymphoma

Additional relevant MeSH terms:
Neoplasms by Histologic Type
Immunoproliferative Disorders
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Antineoplastic Agents
Bortezomib
Enzyme Inhibitors
Pharmacologic Actions
Protease Inhibitors
Lymphatic Diseases
Neoplasms
Therapeutic Uses
Lymphoma, Large-Cell, Immunoblastic
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Lymphoma

ClinicalTrials.gov processed this record on February 08, 2010