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Tanespimycin and Bortezomib in Treating Patients With Advanced Solid Tumors or Lymphomas

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00096005
First received: November 9, 2004
Last updated: February 21, 2014
Last verified: October 2011
  Purpose
This phase I trial is studying the side effects and best dose of giving tanespimycin together with bortezomib in treating patients with advanced solid tumors or lymphomas. (Accrual for lymphoma patients closed as of 11/27/09) Drugs used in chemotherapy, such as tanespimycin, 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 tanespimycin by making cancer cells more sensitive to the drug. Combining tanespimycin with bortezomib may kill more cancer cells.

Condition Intervention Phase
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 Recurrent Adult Burkitt Lymphoma Recurrent Adult Diffuse Large Cell Lymphoma Recurrent Adult Diffuse Mixed Cell Lymphoma Recurrent Adult Diffuse Small Cleaved Cell Lymphoma Recurrent Adult Grade III Lymphomatoid Granulomatosis Recurrent Adult Hodgkin Lymphoma Recurrent Adult Immunoblastic Large Cell Lymphoma Recurrent Adult Lymphoblastic Lymphoma Recurrent Adult T-cell Leukemia/Lymphoma Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma Recurrent Grade 1 Follicular Lymphoma Recurrent Grade 2 Follicular Lymphoma Recurrent Grade 3 Follicular Lymphoma Recurrent Mantle Cell Lymphoma Recurrent Marginal Zone Lymphoma Recurrent Mycosis Fungoides/Sezary Syndrome Recurrent Small Lymphocytic 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 Adult T-cell Leukemia/Lymphoma Stage III Cutaneous T-cell Non-Hodgkin Lymphoma 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 Mycosis Fungoides/Sezary Syndrome 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 Stage IV Adult Immunoblastic Large Cell Lymphoma Stage IV Adult Lymphoblastic Lymphoma Stage IV Adult T-cell Leukemia/Lymphoma Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma Stage IV Grade 1 Follicular Lymphoma Stage IV Grade 2 Follicular Lymphoma Stage IV Grade 3 Follicular Lymphoma Stage IV Mantle Cell Lymphoma Stage IV Marginal Zone Lymphoma Stage IV Mycosis Fungoides/Sezary Syndrome Stage IV Small Lymphocytic Lymphoma Unspecified Adult Solid Tumor, Protocol Specific Waldenström Macroglobulinemia Drug: tanespimycin Drug: bortezomib Other: laboratory biomarker analysis Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: 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):

Primary Outcome Measures:
  • MTD of tanespimycin in combination with bortezomib in the treatment of solid tumors [ Time Frame: At 3 weeks ]
    Defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of the solid tumor patients (at least 2 of a maximum of 6 new patients).

  • Toxicity of tanespimycin in combination with bortezomib in the treatment of solid tumors [ Time Frame: At 3 weeks ]
    Defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 as adverse events that are classified as either possibly, probably, or definitely related to study treatment. Non-hematologic toxicities will be evaluated via the ordinal common toxicity criteria (CTC) standard toxicity grading. Hematologic toxicity measures of thrombocytopenia, neutropenia, and leukopenia will be assessed using continuous variables as the outcome measures (primarily nadir) as well as categorization via CTC standard toxicity grading.

  • Changes in biomarkers in peripheral blood mononuclear cells and tumor specimens from patients with advanced solid tumors or lymphomas [ Time Frame: Baseline, days 4, 8, and 11 of course 1, and at the end of treatment study ]
    Changes in the levels of expressions of HSP70, client proteins, and ubquitination of proteins in PBMC at the different dose levels as well as at the different time points will be descriptively summarized. The degree of proteasome inhibition will be quantitated whenever possible and the results will be displayed graphically and analyzed using simple descriptive statistics.

  • Responses in patients treated with this regimen [ Time Frame: Every 6 weeks ]
    Evaluated using the modified Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease (overall and by tumor group).

  • Time until hematologic nadirs (WBC, ANC, platelets) [ Time Frame: Days 4, 8, and 11 of course 1 and then every 21 days ]
  • Time to progression [ Time Frame: Every 6 weeks ]
  • Time to treatment failure [ Time Frame: At 3 weeks and every 6 weeks ]
    Defined as the time from registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by the patient.


Enrollment: 36
Study Start Date: November 2004
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (chemotherapy and enzyme inhibitor therapy)

Patients receive tanespimycin 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 tanespimycin and bortezomib until the 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.

Drug: tanespimycin
Given IV
Other Name: 17-AAG
Drug: bortezomib
Given IV
Other Names:
  • LDP 341
  • MLN341
  • VELCADE
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

OBJECTIVES:

I. Determine the dose-limiting toxicity and maximum tolerated dose of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) (tanespimycin) and bortezomib in patients with advanced solid tumors or lymphomas (Accrual for Lymphoma Patients Closed as of 11/27/09).

II. 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.

III. Determine responses in patients treated with this regimen. IV. Determine the toxic effects of this regimen in these patients.

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

Patients receive tanespimycin intravenously (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 tanespimycin 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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • Performance status - ECOG 0-2
  • At least 12 weeks
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 9.0 g/dL
  • 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)
  • Creatinine ≤ 2 times ULN
  • 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
  • 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)
  • 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
  • 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
  • More than 4 weeks since prior immunotherapy or biologic therapy
  • No concurrent prophylactic colony-stimulating factors
  • No concurrent immunotherapy, biologic therapy, or gene therapy
  • More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
  • No other concurrent chemotherapy
  • Concurrent steroids (at a stable dose for ≥ 4 weeks) for comorbid conditions (e.g., adrenal insufficiency or rheumatoid arthritis) allowed
  • 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
  • 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00096005

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Charles Erlichman Mayo Clinic
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00096005     History of Changes
Obsolete Identifiers: NCT01646905, NCT01664325
Other Study ID Numbers: NCI-2009-00043
NCI-2009-00043 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
MAYO-MC0214
NCI-6121
CDR0000391837
MC0214 ( Other Identifier: Mayo Clinic )
6121 ( Other Identifier: CTEP )
U01CA069912 ( U.S. NIH Grant/Contract )
P30CA015083 ( U.S. NIH Grant/Contract )
Study First Received: November 9, 2004
Last Updated: February 21, 2014

Additional relevant MeSH terms:
Lymphoma
Syndrome
Leukemia
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Hodgkin Disease
Lymphoma, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, B-Cell, Marginal Zone
Leukemia, Lymphocytic, Chronic, B-Cell
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Lymphoma, Large B-Cell, Diffuse
Burkitt Lymphoma
Lymphoma, T-Cell
Lymphoma, Large-Cell, Immunoblastic
Plasmablastic Lymphoma
Mycoses
Mycosis Fungoides
Sezary Syndrome
Lymphoma, T-Cell, Cutaneous
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Waldenstrom Macroglobulinemia
Lymphoma, Large-Cell, Anaplastic
Lymphomatoid Granulomatosis
Lymphoma, Extranodal NK-T-Cell
Immunoblastic Lymphadenopathy
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders

ClinicalTrials.gov processed this record on September 21, 2017