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Adult Nasal Type Extranodal NK/T-cell LymphomaPhase 1NCT00354185

PXD101 and 17-N-Allylamino-17-Demethoxygeldanamycin in Treating Patients With Metastatic or Unresectable Solid Tumors or Lymphoma

A Phase 1 study testing tanespimycin, belinostat and laboratory biomarker analysis in people with Adult Nasal Type Extranodal NK/T-cell Lymphoma and Anaplastic Large Cell 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
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Trial summary

This phase I trial is studying the side effects and best dose of giving PDX101 together with 17-AAG in treating patients with metastatic or unresectable solid tumors or lymphoma. PDX101 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
tanespimycin, belinostat 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
May 2006to Feb 2008
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

  • Patients must have histologically confirmed malignancy (solid tumor or lymphoma) that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
  • Patients may have received prior treatment with either any HDAC inhibitor therapy or 17AAG, as long as they did not experience dose limiting toxicity (DLT) with these prior treatments; DLTs include
  • Toxicity: neutrophils; DLT: grade 4 toxicity (< 500/μL) for >= 7 days
  • Toxicity: febrile neutropenia; DLT: ANC < 1000/μL of any duration accompanied by fever >= 38.5ºC
  • Toxicity: platelets; DLT: grade 4 toxicity (< 25,000/μL) for >= 7 days or of any duration if accompanied by clinically significant bleeding
  • Toxicity: non-hematologic; DLT: >= grade 3 as per NCI Common Terminology Criteria for Adverse Events, Version 3.0 (except alopecia); for nausea and vomiting, grade 3 toxicity with maximal anti-emetic treatment will be considered dose-limiting; grade 3 diarrhea in spite of maximal anti-diarrheal therapy will be considered dose-limiting; hypersensitivity reactions to 17AAG will not be considered a DLT; asymptomatic grade 3 hypophosphatemia will not be considered a DLT
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  • Toxicity: cardiac; DLT: ≥ grade 3 QTc prolongation
  • ECOG performance status =< 2 (Karnofsky >= 60%)
  • Life expectancy of greater than 12 weeks
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 75,000/mcL
  • Total bilirubin within normal institutional limits
  • AST(SGOT)/ALT(SGPT) =< 2.5 X institutional upper limit of normal
  • Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Eligibility of patients receiving any medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of PXD101 or 17AAG will be determined following review of their case by the Principal Investigator or Study Chair; efforts should be made to switch patients who are taking enzyme-inducing anticonvulsant agents to other medications
  • The effects of PXD101 and 17AAG on the developing human fetus are unknown; for this reason and because HDAC inhibitors as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent document
  • Within 4 weeks of first treatment: Left ventricular ejection fraction ≥ 45% per nuclear cardiac imaging or echocardiography

Who cannot join

  • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered (≤ grade 1) from clinically significant adverse events due to agents administered more than 4 weeks earlier
  • Patients may not be receiving any other investigational agents
  • Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to PXD101; there are no known allergic reactions attributed to compounds of similar chemical or biological composition to 17AAG; patients with known egg allergy should be excluded as the agent is diluted in EPL diluent
  • Patients should not have taken valproic acid, another histone deacetylase inhibitor, for at least 2 weeks prior to enrollment
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements
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  • Pregnant women are excluded from this study because PXD101 is an HDAC inhibitor with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with PXD101, breastfeeding should be discontinued if the mother is treated with PXD101; these potential risks may also apply to other agents used in this study
  • HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with PXD101; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
  • History of allergic reactions to eggs
  • Patients who have significant cardiac disease including heart failure that meets New York Heart Association (NYHA) class III and IV definitions, history of myocardial infarction within 12 months of study entry, ischemic or severs valvular heart disease, uncontrolled dysrhythmias, uncontrolled hypertension, a condition requiring anti-arrhythmic therapy, or poorly controlled or unstable angina pectoris
  • Patients who have a history of serious ventricular arrhythmia (VT or VF, >= 3 beats in a row) or QTc >= 450 msec for men and 470 msec for women or a history of long QT Syndrome
  • Patients taking concomitant medications that prolong or may prolong QTc or may cause Tosade des Pointes

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

Other trials in United States

About this study

Official title: A Phase I Study of PXD101 in Combination With 17-AAG in Advanced Malignancies

This phase I trial is studying the side effects and best dose of giving PDX101 together with 17-AAG in treating patients with metastatic or unresectable solid tumors or lymphoma. PDX101 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer. Drugs used in chemotherapy, such as 17-N-allylamino-17-demethoxygeldanamycin (17-AAG), work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving PXD101 together with 17-AAG may kill more cancer cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate the safety and tolerability of PXD101 and 17-AAG administered to patients with refractory solid tumor malignancies.

II. To determine the maximum tolerated dose (MTD) and recommended phase II dose of PXD101 and 17-AAG in patients with refractory solid tumor malignancies.

SECONDARY OBJECTIVES:

  1. To evaluate the pharmacokinetics of PXD101 and 17-AAG in patients receiving this combination.

II. To evaluate the antitumor activity of this combination, per tumor measurements using the RECIST criteria.

TERTIARY OBJECTIVES:

  1. To evaluate the effect of treatment with PXD101 and 17-AAG on the transcriptional upregulation of targeted genes in tumor and surrogate tissue (PBMCs) by means of RTPCR and incorporation of the chromatin immunoprecipitation assay.

II. To evaluate the effect of this combination treatment on the post translational modification of histones from tumor and surrogate tissue (PBMCs).

OUTLINE: This is a dose-escalation study.

Patients receive 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) IV over 2 hours on days 1, 4, 8, and 11 and PXD101 IV over 30 minutes on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of 17-AAG and PDX101 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. Up to 12 patients are treated at the MTD.

Patients undergo blood collection on days 1 and 4 of course 1 for pharmacokinetic studies.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study.

Being tested
tanespimycin, belinostat, laboratory biomarker analysis, pharmacological study
Medical subject headings
Lymphoma, Extranodal NK-T-Cell, Lymphoma, Large-Cell, Anaplastic, Immunoblastic Lymphadenopathy, Intraocular Lymphoma, Lymphoma, B-Cell, Marginal Zone, Burkitt Lymphoma, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin

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

  • belinostatDrug

    Also called PXD101

    Given IV

  • laboratory biomarker analysisOther

    Correlative studies

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

Study groups in NCT00354185
Study groupRoleWhat they receive
Treatment (tanespimycin, belinostat)ExperimentalPatients receive 17-AAG IV over 2 hours on days 1, 4, 8, and 11 and PXD101 IV over 30 minutes on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of 17-AAG and PDX101 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. Up to 12 patients are treated at the MTD. Patients undergo blood collection on days 1 and 4 of course 1 for pharmacokinetic studies.
Receives: Drug: tanespimycin; Drug: belinostat; Other: laboratory biomarker analysis; Other: pharmacological study

What is being measured

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

  1. Maximum tolerated dose (MTD), based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0

    Measured: Up to 21 days

  2. Number and severity of toxicity incidents, based on the NCI CTCAE v3.0

    Dose-toxicity relationship may be explored by performing exact logistic regression analysis.

    Measured: Up to 2 years

Secondary outcomes (7)

  1. Cmax (observed maximum plasma concentration)

    Summarized by dose level with simple summary statistics. Jonckheere-Terpstra trend test will be performed. Scatterplots will be used.

    Measured: Day 4

  2. Tmax (time to Cmax)

    Summarized by dose level with simple summary statistics.

    Measured: Day 4

  3. AUC0-lqc (the area under the plasma concentration-time curve as determined by the linear trapezoidal rule and where lqc is last quantifiable concentration)

    Summarized by dose level with simple summary statistics. Jonckheere-Terpstra trend test will be performed. Scatterplots will be used.

    Measured: Day 4

  4. AUC0-omega (the area under the plasma concentration-time curve from time 0 to infinity as determined by AUC0-lqc + lqc/-omega)

    Summarized by dose level with simple summary statistics. Jonckheere-Terpstra trend test will be performed. Scatterplots will be used.

    Measured: Day 4

  5. T1/2 (the terminal disposition half-life calculated as ln(2)/-beta)

    Summarized by dose level with simple summary statistics.

    Measured: Day 4

  6. CL where the clearance is calculated by dividing the total dose by AUC0-omega

    Summarized by dose level with simple summary statistics.

    Measured: Day 4

  7. Anti-tumor response (progressive disease [PD], stable disease [SD], a partial response [PR] or a complete response [CR]) as validated by the Response Evaluation Criteria in Solid Tumors (RECIST)

    Ninety-five percent confidence interval for the response rate at the MTD will be constructed using the Wilson score method.

    Measured: Up to 2 years

Timeline

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

  1. First posted20 Jul 2006 (estimated)
  2. Study startMay 2006
  3. Primary completionFeb 2008

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
NCT00354185
Sponsor's protocol ID
NCI-2013-00006
Other IDs
CO 05906, WCCC-CO-05906, NCI-7277, U01CA062491
Status last verified
May 2013
First submitted
19 Jul 2006
Last updated
16 May 2013
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing tanespimycin, belinostat and laboratory biomarker analysis in people with Adult Nasal Type Extranodal NK/T-cell Lymphoma and Anaplastic Large Cell 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 19 inclusion and 12 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 16 May 2013. 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?

Maximum tolerated dose (MTD), based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0 (time frame: Up to 21 days). The study lists 2 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 NCT00354185.

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 16 May 2013.

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