AzTrials
AzTrials

Adult Grade III Lymphomatoid GranulomatosisPhase 1NCT00096005

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

A Phase 1 study testing tanespimycin, bortezomib and laboratory biomarker analysis in people with Adult Grade III Lymphomatoid Granulomatosis and AIDS-related Peripheral/Systemic Lymphoma, run by National Cancer Institute (NCI) at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
tanespimycin, bortezomib and laboratory biomarker analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
36 participants
Where
1 siteUnited States
Study dates
Nov 2004to Mar 2010
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 63Show fewer
  • 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

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Mayo Clinic

    Rochester, Minnesota, 55905

Other trials in United States

About this study

Official title: A Phase I Trial Of 17-Allylaminogeldanamycin (17-AAG) And PS341 In Advanced Malignancies

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.

Read the detailed description

OBJECTIVES:

  1. 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.

Being tested
tanespimycin, bortezomib, laboratory biomarker analysis
Medical subject headings
Lymphoma, Large-Cell, Anaplastic, Immunoblastic Lymphadenopathy, Lymphoma, B-Cell, Marginal Zone, Burkitt Lymphoma, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin, Hodgkin Disease, Lymphoma, Large-Cell, Immunoblastic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • tanespimycinDrug

    Also called 17-AAG

    Given IV

  • bortezomibDrug

    Also called LDP 341, MLN341, VELCADE

    Given IV

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT00096005
Study groupRoleWhat they receive
Treatment (chemotherapy and enzyme inhibitor therapy)ExperimentalPatients 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.
Receives: Drug: tanespimycin; Drug: bortezomib; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. MTD of tanespimycin in combination with bortezomib in the treatment of solid tumors

    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).

    Measured: At 3 weeks

  2. Toxicity of tanespimycin in combination with bortezomib in the treatment of solid tumors

    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.

    Measured: At 3 weeks

  3. Changes in biomarkers in peripheral blood mononuclear cells and tumor specimens from patients with advanced solid tumors or lymphomas

    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.

    Measured: Baseline, days 4, 8, and 11 of course 1, and at the end of treatment study

  4. Responses in patients treated with this regimen

    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).

    Measured: Every 6 weeks

  5. Time until hematologic nadirs (WBC, ANC, platelets)

    Measured: Days 4, 8, and 11 of course 1 and then every 21 days

  6. Time to progression

    Measured: Every 6 weeks

  7. Time to treatment failure

    Defined as the time from registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by the patient.

    Measured: At 3 weeks and every 6 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Nov 2004 (estimated)
  2. Study startNov 2004
  3. Primary completionMar 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
36 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00096005
Sponsor's protocol ID
NCI-2009-00043
Other IDs
NCI-2009-00043, MAYO-MC0214, NCI-6121, CDR0000391837, MC0214, 6121, U01CA069912, P30CA015083
Status last verified
Oct 2011
First submitted
9 Nov 2004
Last updated
24 Feb 2014
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing tanespimycin, bortezomib and laboratory biomarker analysis in people with Adult Grade III Lymphomatoid Granulomatosis and AIDS-related Peripheral/Systemic Lymphoma, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 63 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 24 Feb 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early. Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

MTD of tanespimycin in combination with bortezomib in the treatment of solid tumors (time frame: At 3 weeks). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00096005.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2014.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in