Brief Title
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
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.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Maximum tolerated dose of alvespimycin hydrochloride
Secondary Outcome
Tumor response assessed by tumor measurements
Condition
Anaplastic Large Cell Lymphoma
Intervention
alvespimycin hydrochloride
Study Arms / Comparison Groups
Treatment (alvespimycin hydrochloride)
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
60
Start Date
July 2004
Primary Completion Date
June 2010
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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Chandra Belani, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00089271
Organization ID
NCI-2012-02620
Secondary IDs
PCI-03-153
Responsible Party
Sponsor
Study Sponsor
National Cancer Institute (NCI)
Study Sponsor
Chandra Belani, Principal Investigator, University of Pittsburgh
Verification Date
January 2013