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

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.

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 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