Clinical trial NCT00089271: 17-DMAG in Treating Patients With Metastatic or Unresectable Solid Tumors or Lymphomas
Official title: A Phase I Study Of 17-Dimethylaminoethylamino-17-Demethoxygeldanamycin, (17-DMAG) (NSC 707545) In Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-cell Lymphoma
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Intraocular Lymphoma
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 Hodgkin 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
Splenic Marginal Zone 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 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 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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2004-08-05
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase I trial is studying the side effects and best dose of 17-DMAG in treating patients with metastatic or unresectable solid tumors or lymphomas. Drugs used in chemotherapy, such as 17-DMAG, work in different ways to stop cancer cells from dividing so they stop growing or die

Detailed description: PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) in patients with metastatic or unresectable solid tumors or lymphomas.

II. Determine the safety and toxicity of this drug in these patients. III. Determine the pharmacokinetics and pharmacodynamics of this drug in these patients.

IV. Determine the recommended phase II dose of this drug for future studies.

SECONDARY OBJECTIVES:

I. Determine tumor response in patients treated with this drug.

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

Patients receive 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) IV over 1-6 hours on days 1-3 or 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 1-2 patients receive accelerated escalating doses of 17-DMAG until at least 1 of 2 patients experience dose-limiting toxicity (DLT). Cohorts are then expanded to 3-6 patients who receive escalating doses (in a standard manner) of 17-DMAG 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 DLT.

Patients are followed at 4 weeks.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed solid tumor or lymphoma

  * Metastatic or unresectable disease
* Standard curative or palliative measures do not exist or are no longer effective
* No known brain metastases
* Performance status - ECOG 0-2
* Performance status - Karnofsky 60-100%
* More than 12 weeks
* Absolute neutrophil count ≥ 1,500/mm\^3
* Platelet count ≥ 100,000/mm\^3
* Hemoglobin ≥ 9.0 g/dL
* ALT and AST ≤ 1.5 times upper limit of normal (ULN)
* Bilirubin ≤ normal
* Creatinine ≤ 1.25 times ULN
* 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 or active ischemic heart disease within the past year
* No New York Heart Association class III or IV congestive heart failure
* No poorly controlled angina
* No uncontrolled dysrhythmia requiring medication
* No left bundle branch block
* No history of congenital long QT syndrome
* No other significant cardiac disease
* Pulse oximetry at rest or on exercise \> 88%
* No symptomatic pulmonary disease (e.g., chronic obstructive or restrictive pulmonary disease, etc.) or any of the following are allowed:

  * Pulmonary disease requiring medication
  * History of dyspnea, dyspnea on exertion, or paroxysmal nocturnal dyspnea
  * Patients meeting the Medicare criteria for home oxygen or are on oxygen
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective double barrier contraception 1 week before, during, and for at least 2 weeks after study participation
* No uncontrolled illness
* No active or ongoing infection
* No history of allergic reaction attributed to compounds of similar chemical or biological composition to 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG)
* No psychiatric illness or social situation that would preclude study compliance
* No concurrent routine colony-stimulating factors (e.g., filgrastim \[G-CSF\] or sargramostim \[GM-CSF\])
* At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
* Concurrent hormonal therapy allowed
* At least 4 weeks since prior radiotherapy and recovered
* No prior radiation that included the heart in the field (e.g., mantle)
* No concurrent combination antiretroviral therapy for HIV-positive patients
* No other concurrent anticancer agents or therapies
* No concurrent medication that would prolong the QTc interval
* No other concurrent investigational agents

Primary outcomes:
measure: Maximum tolerated dose of alvespimycin hydrochloride
timeFrame: 21 days
measure: Toxicity graded using the NCI CTCAE version 3.0
timeFrame: Up to 4 weeks
measure: Recommended phase II dose (RP2D) of alvespimycin hydrochloride for future studies determined by toxicity assessments
timeFrame: 21 days
measure: Pharmacokinetics of alvespimycin hydrochloride in blood, urine, and tumor tissue
timeFrame: 21 days
Secondary outcomes:
measure: Tumor response assessed by tumor measurements
timeFrame: Up to 4 weeks
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Chandra Belani
role: PRINCIPAL_INVESTIGATOR
References: