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

NCT ID: NCT00096005

Last Updated: 2014-02-24

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-11-30

Brief Summary

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.

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.

Conditions

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

Study Design

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

Study Groups

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.

Group Type: EXPERIMENTAL

tanespimycin

Intervention Type: DRUG

Given IV

bortezomib

Intervention Type: DRUG

Given IV

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

tanespimycin

Given IV

Intervention Type: DRUG

bortezomib

Given IV

Intervention Type: DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

17-AAG; LDP 341; MLN341; VELCADE

Eligibility 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

• 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

Charles Erlichman

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

Other Identifiers

NCI-2009-00043

Identifier Type: REGISTRY

Identifier Source: secondary_id

MAYO-MC0214

Identifier Type: -

Identifier Source: secondary_id

NCI-6121

Identifier Type: -

Identifier Source: secondary_id

CDR0000391837

Identifier Type: -

Identifier Source: secondary_id

MC0214

Identifier Type: OTHER

Identifier Source: secondary_id

6121

Identifier Type: OTHER

Identifier Source: secondary_id

U01CA069912

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA015083

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00043

Identifier Type: -

Identifier Source: org_study_id

NCT01646905

Identifier Type: -

Identifier Source: nct_alias

NCT01664325

Identifier Type: -

Identifier Source: nct_alias